Trial Outcomes & Findings for Immune Profile in Subjects With New Onset Type 1 Diabetes (NCT NCT02801942)

Results Overview

Peripheral blood samples were collected from both healthy and NOT1D participants at the indicated time points for the analysis of leukocyte subsets from Monocyte Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. Generalized linear mixed models were used to analyze data separately for each flow cytometry cell type to provide estimates for comparisons. Fixed categorical were group, sample type, and the interaction of group with sample type, where Group was HV or NOT1D, and sample type was peripheral blood, core biopsy or FNA. The analysis was based upon Safety Population which comprised of all participants who complete any study assessment. Only those participants with data available at specific time point were analyzed (represented by n=x in category titles). NA indicates that data was not available.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

22 participants

Primary outcome timeframe

Pre Biopsy session on Day 1

Results posted on

2019-02-27

Participant Flow

This was a multi-center, non-drug treatment study to compare differences in immune cells derived from the inguinal lymph nodes (iLN) and peripheral blood of New Onset Type 1 Diabetes Mellitus (NOT1D) participants and healthy volunteers. Participants were enrolled at a single center in United Kingdom.

Participants underwent iLN biopsies by two methods; fine-needle aspirate (FNA) and core needle biopsy. Participants underwent screening followed by study visits and follow-up. A total of 43 participants were screened, of which, 21 were considered as screen failures and 22 were enrolled into the study.

Participant milestones

Participant milestones
Measure	Healthy Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Overall Study STARTED	12	10
Overall Study COMPLETED	12	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Immune Profile in Subjects With New Onset Type 1 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.	Total n=22 Participants Total of all reporting groups
Age, Continuous	28.6 Years STANDARD_DEVIATION 5.53 • n=5 Participants	27.0 Years STANDARD_DEVIATION 5.35 • n=7 Participants	27.9 Years STANDARD_DEVIATION 5.38 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	6 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants

PRIMARY outcome

Timeframe: Pre Biopsy session on Day 1

Population: Safety Population

Peripheral blood samples were collected from both healthy and NOT1D participants at the indicated time points for the analysis of leukocyte subsets from Monocyte Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. Generalized linear mixed models were used to analyze data separately for each flow cytometry cell type to provide estimates for comparisons. Fixed categorical were group, sample type, and the interaction of group with sample type, where Group was HV or NOT1D, and sample type was peripheral blood, core biopsy or FNA. The analysis was based upon Safety Population which comprised of all participants who complete any study assessment. Only those participants with data available at specific time point were analyzed (represented by n=x in category titles). NA indicates that data was not available.

Outcome measures

Outcome measures
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including B Lymphocytes, Classical B Lymphocytes, Double Negative B Lymphocytes, Naive B Lymphocytes, Plasmablast and Transitional B Lymphocytes in Blood Circulating B Lymphocytes; n=12, 10	16.54 Percentage of B lymphocytes Standard Error 2.229	14.23 Percentage of B lymphocytes Standard Error 2.442
Percentage of Leukocyte Subsets Including B Lymphocytes, Classical B Lymphocytes, Double Negative B Lymphocytes, Naive B Lymphocytes, Plasmablast and Transitional B Lymphocytes in Blood Classical B Lymphocytes; n=12, 10	19.37 Percentage of B lymphocytes Standard Error 1.616	15.83 Percentage of B lymphocytes Standard Error 1.771
Percentage of Leukocyte Subsets Including B Lymphocytes, Classical B Lymphocytes, Double Negative B Lymphocytes, Naive B Lymphocytes, Plasmablast and Transitional B Lymphocytes in Blood Double Negative B Lymphocytes; n=12, 10	3.25 Percentage of B lymphocytes Standard Error 1.250	6.26 Percentage of B lymphocytes Standard Error 1.370
Percentage of Leukocyte Subsets Including B Lymphocytes, Classical B Lymphocytes, Double Negative B Lymphocytes, Naive B Lymphocytes, Plasmablast and Transitional B Lymphocytes in Blood Naive B Lymphocytes; n=12, 10	59.81 Percentage of B lymphocytes Standard Error 3.021	62.32 Percentage of B lymphocytes Standard Error 3.310
Percentage of Leukocyte Subsets Including B Lymphocytes, Classical B Lymphocytes, Double Negative B Lymphocytes, Naive B Lymphocytes, Plasmablast and Transitional B Lymphocytes in Blood Plasmablast ; n=11, 10	NA Percentage of B lymphocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.	NA Percentage of B lymphocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.
Percentage of Leukocyte Subsets Including B Lymphocytes, Classical B Lymphocytes, Double Negative B Lymphocytes, Naive B Lymphocytes, Plasmablast and Transitional B Lymphocytes in Blood Transitional B Lymphocytes; n=12, 10	NA Percentage of B lymphocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.	NA Percentage of B lymphocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.

PRIMARY outcome

Timeframe: Biopsy session on Day 1

Population: Safety Population

Samples were collected including up to two FNA passages of iLN and up to five core biopsies of iLN at the indicated time point from both healthy and NOT1D participants for the analysis of leukocyte subsets from Monocyte Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. Generalized linear mixed models were used to analyze data separately for each flow cytometry cell type to provide estimates for comparisons. Fixed categorical were group, sample type, and the interaction of group with sample type, where Group was HV or NOT1D, and sample type was peripheral blood, core biopsy or FNA. Only those participants with data available at specific time point were analyzed (represented by n=x in category titles). NA indicates that data was not available.

Outcome measures

Outcome measures
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including B Lymphocytes, Classical B Lymphocytes, Double Negative B Lymphocytes, Naive B Lymphocytes, Plasmablast and Transitional B Lymphocytes in iLN Transitional B Lymphocytes; ; n=3, 2	NA Percentage of B lymphocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.	NA Percentage of B lymphocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.
Percentage of Leukocyte Subsets Including B Lymphocytes, Classical B Lymphocytes, Double Negative B Lymphocytes, Naive B Lymphocytes, Plasmablast and Transitional B Lymphocytes in iLN Circulating B Lymphocytes; n=9, 10	15.51 Percentage of B lymphocytes Standard Error 1.860	12.14 Percentage of B lymphocytes Standard Error 1.898
Percentage of Leukocyte Subsets Including B Lymphocytes, Classical B Lymphocytes, Double Negative B Lymphocytes, Naive B Lymphocytes, Plasmablast and Transitional B Lymphocytes in iLN Classical B Lymphocytes; n=9, 10	38.78 Percentage of B lymphocytes Standard Error 4.119	30.19 Percentage of B lymphocytes Standard Error 4.130
Percentage of Leukocyte Subsets Including B Lymphocytes, Classical B Lymphocytes, Double Negative B Lymphocytes, Naive B Lymphocytes, Plasmablast and Transitional B Lymphocytes in iLN Double Negative B Lymphocytes; n=9, 10	8.68 Percentage of B lymphocytes Standard Error 1.668	10.26 Percentage of B lymphocytes Standard Error 1.651
Percentage of Leukocyte Subsets Including B Lymphocytes, Classical B Lymphocytes, Double Negative B Lymphocytes, Naive B Lymphocytes, Plasmablast and Transitional B Lymphocytes in iLN Naive B Lymphocytes; n=9, 10	35.83 Percentage of B lymphocytes Standard Error 3.761	44.13 Percentage of B lymphocytes Standard Error 3.621
Percentage of Leukocyte Subsets Including B Lymphocytes, Classical B Lymphocytes, Double Negative B Lymphocytes, Naive B Lymphocytes, Plasmablast and Transitional B Lymphocytes in iLN Plasmablast; n=4, 8	NA Percentage of B lymphocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.	NA Percentage of B lymphocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.

PRIMARY outcome

Timeframe: Pre Biopsy session on Day 1

Population: Safety Population

Peripheral blood samples were collected from both healthy and NOT1D participants at the indicated time points for the analysis of leukocyte subsets from Monocyte Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. Generalized linear mixed models were used to analyze data separately for each flow cytometry cell type to provide estimates for comparisons. Fixed categorical were group, sample type, and the interaction of group with sample type, where Group was HV or NOT1D, and sample type was peripheral blood, core biopsy or FNA. NA indicates that data was not available.

Outcome measures

Outcome measures
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including B-cells, Clusters of Differentiation 56 Positive (CD56+) CD16+ , CD56bright Natural Killer (NK) Cells, CD56lo CD16+, CD56lo CD16 Negative (CD56lo CD16-), Dendritic Cells, NK Cells in Blood CD56lo CD16+	7.96 Percentage of mononuclear cells Standard Error 1.011	8.24 Percentage of mononuclear cells Standard Error 1.108
Percentage of Leukocyte Subsets Including B-cells, Clusters of Differentiation 56 Positive (CD56+) CD16+ , CD56bright Natural Killer (NK) Cells, CD56lo CD16+, CD56lo CD16 Negative (CD56lo CD16-), Dendritic Cells, NK Cells in Blood B-cells	8.50 Percentage of mononuclear cells Standard Error 0.589	7.58 Percentage of mononuclear cells Standard Error 0.645
Percentage of Leukocyte Subsets Including B-cells, Clusters of Differentiation 56 Positive (CD56+) CD16+ , CD56bright Natural Killer (NK) Cells, CD56lo CD16+, CD56lo CD16 Negative (CD56lo CD16-), Dendritic Cells, NK Cells in Blood CD56+CD16+	NA Percentage of mononuclear cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.	NA Percentage of mononuclear cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.
Percentage of Leukocyte Subsets Including B-cells, Clusters of Differentiation 56 Positive (CD56+) CD16+ , CD56bright Natural Killer (NK) Cells, CD56lo CD16+, CD56lo CD16 Negative (CD56lo CD16-), Dendritic Cells, NK Cells in Blood CD56bright NK cells	0.36 Percentage of mononuclear cells Standard Error 0.042	0.30 Percentage of mononuclear cells Standard Error 0.046
Percentage of Leukocyte Subsets Including B-cells, Clusters of Differentiation 56 Positive (CD56+) CD16+ , CD56bright Natural Killer (NK) Cells, CD56lo CD16+, CD56lo CD16 Negative (CD56lo CD16-), Dendritic Cells, NK Cells in Blood CD56lo CD16-	0.24 Percentage of mononuclear cells Standard Error 0.036	0.23 Percentage of mononuclear cells Standard Error 0.040
Percentage of Leukocyte Subsets Including B-cells, Clusters of Differentiation 56 Positive (CD56+) CD16+ , CD56bright Natural Killer (NK) Cells, CD56lo CD16+, CD56lo CD16 Negative (CD56lo CD16-), Dendritic Cells, NK Cells in Blood Dendritic cells	0.93 Percentage of mononuclear cells Standard Error 0.080	0.87 Percentage of mononuclear cells Standard Error 0.088
Percentage of Leukocyte Subsets Including B-cells, Clusters of Differentiation 56 Positive (CD56+) CD16+ , CD56bright Natural Killer (NK) Cells, CD56lo CD16+, CD56lo CD16 Negative (CD56lo CD16-), Dendritic Cells, NK Cells in Blood NK cells	8.71 Percentage of mononuclear cells Standard Error 0.999	8.84 Percentage of mononuclear cells Standard Error 1.095

PRIMARY outcome

Timeframe: Biopsy session on Day 1

Population: Safety Population

Samples were collected including up to two FNA passages of iLN and up to five core biopsies of iLN at the indicated time point from both healthy and NOT1D participants for the analysis of leukocyte subsets from Monocyte Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. Generalized linear mixed models were used to analyze data separately for each flow cytometry cell type to provide estimates for comparisons. Fixed categorical were group, sample type, and the interaction of group with sample type, where Group was HV or NOT1D, and sample type was peripheral blood, core biopsy or FNA. Only those participants with data available at specific time point were analyzed (represented by n=x in category titles). NA indicates that data was not available.

Outcome measures

Outcome measures
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including B-cells, CD56+ CD16+, CD56bright NK Cells, CD56lo CD16+, CD56lo CD16-, Dendritic Cells, NK Cells in iLN B-cells; n=9, 10	8.88 Percentage of mononuclear cells Standard Error 1.641	7.34 Percentage of mononuclear cells Standard Error 1.512
Percentage of Leukocyte Subsets Including B-cells, CD56+ CD16+, CD56bright NK Cells, CD56lo CD16+, CD56lo CD16-, Dendritic Cells, NK Cells in iLN CD56+CD16+; n=8, 8	NA Percentage of mononuclear cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.	NA Percentage of mononuclear cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.
Percentage of Leukocyte Subsets Including B-cells, CD56+ CD16+, CD56bright NK Cells, CD56lo CD16+, CD56lo CD16-, Dendritic Cells, NK Cells in iLN CD56bright NK cells; n=9, 10	0.54 Percentage of mononuclear cells Standard Error 0.098	0.50 Percentage of mononuclear cells Standard Error 0.101
Percentage of Leukocyte Subsets Including B-cells, CD56+ CD16+, CD56bright NK Cells, CD56lo CD16+, CD56lo CD16-, Dendritic Cells, NK Cells in iLN CD56lo CD16+; n=9, 10	0.68 Percentage of mononuclear cells Standard Error 0.173	0.69 Percentage of mononuclear cells Standard Error 0.184
Percentage of Leukocyte Subsets Including B-cells, CD56+ CD16+, CD56bright NK Cells, CD56lo CD16+, CD56lo CD16-, Dendritic Cells, NK Cells in iLN CD56lo CD16-; n=8, 9	0.19 Percentage of mononuclear cells Standard Error 0.043	0.21 Percentage of mononuclear cells Standard Error 0.040
Percentage of Leukocyte Subsets Including B-cells, CD56+ CD16+, CD56bright NK Cells, CD56lo CD16+, CD56lo CD16-, Dendritic Cells, NK Cells in iLN Dendritic cells; n=9, 10	0.45 Percentage of mononuclear cells Standard Error 0.100	0.39 Percentage of mononuclear cells Standard Error 0.081
Percentage of Leukocyte Subsets Including B-cells, CD56+ CD16+, CD56bright NK Cells, CD56lo CD16+, CD56lo CD16-, Dendritic Cells, NK Cells in iLN NK cells; n=9, 10	1.43 Percentage of mononuclear cells Standard Error 0.324	1.50 Percentage of mononuclear cells Standard Error 0.364

PRIMARY outcome

Timeframe: Pre Biopsy session on Day 1

Population: Safety Population

Peripheral blood samples were collected from both healthy and NOT1D participants at the indicated time points for the analysis of leukocyte subsets from Monocyte Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. Generalized linear mixed models were used to analyze data separately for each flow cytometry cell type to provide estimates for comparisons. Fixed categorical were group, sample type, and the interaction of group with sample type, where Group was HV or NOT1D, and sample type was peripheral blood, core biopsy or FNA. NA indicates that data was not available.

Outcome measures

Outcome measures
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including CD56+CD16+, CD56bright NK Cells, CD56lo CD16+ and CD56lo CD16- in Blood CD56bright NK cells	5.02 Percentage of NK cells Standard Error 0.894	3.99 Percentage of NK cells Standard Error 0.980
Percentage of Leukocyte Subsets Including CD56+CD16+, CD56bright NK Cells, CD56lo CD16+ and CD56lo CD16- in Blood CD56lo CD16+	89.71 Percentage of NK cells Standard Error 1.567	92.40 Percentage of NK cells Standard Error 1.717
Percentage of Leukocyte Subsets Including CD56+CD16+, CD56bright NK Cells, CD56lo CD16+ and CD56lo CD16- in Blood CD56+CD16+	NA Percentage of NK cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.	NA Percentage of NK cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.
Percentage of Leukocyte Subsets Including CD56+CD16+, CD56bright NK Cells, CD56lo CD16+ and CD56lo CD16- in Blood CD56lo CD16-	3.11 Percentage of NK cells Standard Error 0.497	2.70 Percentage of NK cells Standard Error 0.545

PRIMARY outcome

Timeframe: Biopsy session on Day 1

Population: Safety Population

Samples were collected including up to two FNA passages of iLN and up to five core biopsies of iLN at the indicated time point from both healthy and NOT1D participants for the analysis of leukocyte subsets from Monocyte Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. Generalized linear mixed models were used to analyze data separately for each flow cytometry cell type to provide estimates for comparisons. Fixed categorical were group, sample type, and the interaction of group with sample type, where Group was HV or NOT1D, and sample type was peripheral blood, core biopsy or FNA. Only those participants with data available at specific time point were analyzed (represented by n=x in category titles). NA indicates that data was not available.

Outcome measures

Outcome measures
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including CD56+CD16+, CD56bright NK Cells CD56lo CD16+ and CD56lo CD16- in iLN CD56+CD16+; n=8, 8	NA Percentage of NK cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.	NA Percentage of NK cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.
Percentage of Leukocyte Subsets Including CD56+CD16+, CD56bright NK Cells CD56lo CD16+ and CD56lo CD16- in iLN CD56bright NK cells; n=9, 10	41.85 Percentage of NK cells Standard Error 3.999	35.01 Percentage of NK cells Standard Error 3.868
Percentage of Leukocyte Subsets Including CD56+CD16+, CD56bright NK Cells CD56lo CD16+ and CD56lo CD16- in iLN CD56lo CD16+; n=9, 10	37.12 Percentage of NK cells Standard Error 6.220	45.01 Percentage of NK cells Standard Error 4.900
Percentage of Leukocyte Subsets Including CD56+CD16+, CD56bright NK Cells CD56lo CD16+ and CD56lo CD16- in iLN CD56lo CD16-; n=8, 9	12.80 Percentage of NK cells Standard Error 1.855	14.26 Percentage of NK cells Standard Error 1.490

PRIMARY outcome

Timeframe: Pre Biopsy session on Day 1

Population: Safety Population

Peripheral blood samples were collected from both healthy and NOT1D participants at the indicated time points for the analysis of leukocyte subsets from Monocyte Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. Generalized linear mixed models were used to analyze data separately for each flow cytometry cell type to provide estimates for comparisons. Fixed categorical were group, sample type, and the interaction of group with sample type, where Group was HV or NOT1D, and sample type was peripheral blood, core biopsy or FNA.

Outcome measures

Outcome measures
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including Myeloid Dendritic Cells and Plasmacytoid Dendritic Cells in Blood Myeloid Dendritic cells	51.78 Percentage of total dendritic cells Standard Error 3.073	50.45 Percentage of total dendritic cells Standard Error 3.366
Percentage of Leukocyte Subsets Including Myeloid Dendritic Cells and Plasmacytoid Dendritic Cells in Blood Plasmacytoid Dendritic cells	45.51 Percentage of total dendritic cells Standard Error 3.140	47.36 Percentage of total dendritic cells Standard Error 3.440

PRIMARY outcome

Timeframe: Biopsy session on Day 1

Population: Safety Population

Samples were collected including up to two FNA passages of iLN and up to five core biopsies of iLN at the indicated time point from both healthy and NOT1D participants for the analysis of leukocyte subsets from Monocyte Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. Generalized linear mixed models were used to analyze data separately for each flow cytometry cell type to provide estimates for comparisons. Fixed categorical were group, sample type, and the interaction of group with sample type, where Group was HV or NOT1D, and sample type was peripheral blood, core biopsy or FNA.Only those participants with data available at specific time point were analyzed (represented by n=x in category titles).

Outcome measures

Outcome measures
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including Myeloid Dendritic Cells and Plasmacytoid Dendritic Cells in iLN Myeloid Dendritic cells; n=8, 10	42.96 Percentage of total dendritic cells Standard Error 3.870	30.72 Percentage of total dendritic cells Standard Error 4.128
Percentage of Leukocyte Subsets Including Myeloid Dendritic Cells and Plasmacytoid Dendritic Cells in iLN Plasmacytoid Dendritic cells; n=9, 9	57.43 Percentage of total dendritic cells Standard Error 4.426	68.30 Percentage of total dendritic cells Standard Error 5.372

PRIMARY outcome

Timeframe: Pre Biopsy session on Day 1

Population: Safety Population

Peripheral blood samples were collected from both healthy and NOT1D participants at the indicated time points for the analysis of leukocyte subsets from Monocyte Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. NA indicates that data was not available.

Outcome measures

Outcome measures
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including CD14+ CD16+ Monocytes, CD14+ Monocytes, and CD16+ Monocytes in Blood CD14+ monocytes	NA Percentage of monocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis	NA Percentage of monocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis
Percentage of Leukocyte Subsets Including CD14+ CD16+ Monocytes, CD14+ Monocytes, and CD16+ Monocytes in Blood CD16+ monocytes	NA Percentage of monocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis	NA Percentage of monocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis
Percentage of Leukocyte Subsets Including CD14+ CD16+ Monocytes, CD14+ Monocytes, and CD16+ Monocytes in Blood CD14+ CD16+ monocytes	NA Percentage of monocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis	NA Percentage of monocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis

PRIMARY outcome

Timeframe: Biopsy session on Day 1

Population: Safety Population

Samples were collected including up to two FNA passages of iLN and up to five core biopsies of iLN at the indicated time point from both healthy and NOT1D participants for the analysis of leukocyte subsets from Monocyte Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. Only those participants with data available at specific time point were analyzed (represented by n=x in category titles). NA indicates that data was not available.

Outcome measures

Outcome measures
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including CD14+ CD16+ Monocytes, CD14+ Monocytes and CD16+ Monocytes in iLN CD14+ CD16+ monocytes; n=0, 1	—	NA Percentage of monocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.
Percentage of Leukocyte Subsets Including CD14+ CD16+ Monocytes, CD14+ Monocytes and CD16+ Monocytes in iLN CD14+ monocytes; n=7, 4	NA Percentage of monocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.	NA Percentage of monocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.
Percentage of Leukocyte Subsets Including CD14+ CD16+ Monocytes, CD14+ Monocytes and CD16+ Monocytes in iLN CD16+ monocytes; n=0, 2	—	NA Percentage of monocytes Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.

PRIMARY outcome

Timeframe: Pre Biopsy session on Day 1

Population: Safety Population

Peripheral blood samples were collected from both healthy and NOT1D participants at the indicated time points for the analysis of leukocyte subsets from T cell Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. Generalized linear mixed models were used to analyze data separately for each flow cytometry cell type to provide estimates for comparisons. Fixed categorical were group, sample type, and the interaction of group with sample type, where Group was HV or NOT1D, and sample type was peripheral blood, core biopsy or FNA.

Outcome measures

Outcome measures
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including CD45RA+ Effector Memory CD8, Central Memory CD8, Effector Memory CD8, Naive CD8 and Stem Cell Memory-like CD8 Cells in Blood CD45RA+ Effector Memory CD8	29.89 Percentage of CD8 T cells Standard Error 4.267	28.10 Percentage of CD8 T cells Standard Error 4.674
Percentage of Leukocyte Subsets Including CD45RA+ Effector Memory CD8, Central Memory CD8, Effector Memory CD8, Naive CD8 and Stem Cell Memory-like CD8 Cells in Blood Central Memory CD8	7.13 Percentage of CD8 T cells Standard Error 1.537	6.98 Percentage of CD8 T cells Standard Error 1.684
Percentage of Leukocyte Subsets Including CD45RA+ Effector Memory CD8, Central Memory CD8, Effector Memory CD8, Naive CD8 and Stem Cell Memory-like CD8 Cells in Blood Effector Memory CD8	19.22 Percentage of CD8 T cells Standard Error 2.223	14.84 Percentage of CD8 T cells Standard Error 2.435
Percentage of Leukocyte Subsets Including CD45RA+ Effector Memory CD8, Central Memory CD8, Effector Memory CD8, Naive CD8 and Stem Cell Memory-like CD8 Cells in Blood Stem Cell Memory-like CD8	1.34 Percentage of CD8 T cells Standard Error 0.206	1.37 Percentage of CD8 T cells Standard Error 0.225
Percentage of Leukocyte Subsets Including CD45RA+ Effector Memory CD8, Central Memory CD8, Effector Memory CD8, Naive CD8 and Stem Cell Memory-like CD8 Cells in Blood Naive CD8	34.38 Percentage of CD8 T cells Standard Error 3.863	40.44 Percentage of CD8 T cells Standard Error 4.231

PRIMARY outcome

Timeframe: Biopsy session on Day 1

Population: Safety Population

Samples were collected including up to two FNA passages of iLN and up to five core biopsies of iLN at the indicated time point from both healthy and NOT1D participants for the analysis of leukocyte subsets from T cell Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. Generalized linear mixed models were used to analyze data separately for each flow cytometry cell type to provide estimates for comparisons. Fixed categorical were group, sample type, and the interaction of group with sample type, where Group was HV or NOT1D, and sample type was peripheral blood, core biopsy or FNA.

Outcome measures

Outcome measures
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including CD45RA+ Effector Memory CD8, Central Memory CD8, Effector Memory CD8, Naive CD8 and Stem Cell Memory-like CD8 Cells in iLN Effector Memory CD8	13.74 Percentage of CD8 T cells Standard Error 1.867	15.59 Percentage of CD8 T cells Standard Error 2.074
Percentage of Leukocyte Subsets Including CD45RA+ Effector Memory CD8, Central Memory CD8, Effector Memory CD8, Naive CD8 and Stem Cell Memory-like CD8 Cells in iLN Naive CD8	55.12 Percentage of CD8 T cells Standard Error 4.259	54.45 Percentage of CD8 T cells Standard Error 4.700
Percentage of Leukocyte Subsets Including CD45RA+ Effector Memory CD8, Central Memory CD8, Effector Memory CD8, Naive CD8 and Stem Cell Memory-like CD8 Cells in iLN Stem Cell Memory-like CD8	1.69 Percentage of CD8 T cells Standard Error 0.316	2.36 Percentage of CD8 T cells Standard Error 0.377
Percentage of Leukocyte Subsets Including CD45RA+ Effector Memory CD8, Central Memory CD8, Effector Memory CD8, Naive CD8 and Stem Cell Memory-like CD8 Cells in iLN CD45RA+ Effector Memory CD8	14.54 Percentage of CD8 T cells Standard Error 2.094	13.34 Percentage of CD8 T cells Standard Error 2.330
Percentage of Leukocyte Subsets Including CD45RA+ Effector Memory CD8, Central Memory CD8, Effector Memory CD8, Naive CD8 and Stem Cell Memory-like CD8 Cells in iLN Central Memory CD8	5.55 Percentage of CD8 T cells Standard Error 0.978	6.21 Percentage of CD8 T cells Standard Error 1.093

Timeframe: Biopsy session on Day 1

Population: Safety Population

Samples were collected including up to two FNA passages of iLN and up to five core biopsies of iLN at the indicated time point from both healthy and NOT1D participants for the analysis of leukocyte subsets from T cell Panel. Candidate biomarkers associated with either location of cells and/or disease-status were identified using flow cytometry technique. Generalized linear mixed models were used to analyze data separately for each flow cytometry cell type to provide estimates for comparisons. Fixed categorical were group, sample type, and the interaction of group with sample type, where Group was HV or NOT1D, and sample type was peripheral blood, core biopsy or FNA. Only those participants with data available at specific time point were analyzed (represented by n=x in category titles). NA indicates that data was not available.

Outcome measures
Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Number of Participants Who Appreciated Receiving Study Feedback	12 Participants	10 Participants

Adverse Events

Healthy Participants

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Participants With NOT1D

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Healthy Participants n=12 participants at risk Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 participants at risk NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Gastrointestinal disorders Nausea	8.3% 1/12 • Number of events 1 • Serious adverse events (SAEs) and non-serious adverse events (non-SAEs) were collected up to Day 14. SAEs and Non-SAEs were reported for Safety Population which comprised of all participants who completed any study assessment.	0.00% 0/10 • Serious adverse events (SAEs) and non-serious adverse events (non-SAEs) were collected up to Day 14. SAEs and Non-SAEs were reported for Safety Population which comprised of all participants who completed any study assessment.
General disorders Fatigue	8.3% 1/12 • Number of events 1 • Serious adverse events (SAEs) and non-serious adverse events (non-SAEs) were collected up to Day 14. SAEs and Non-SAEs were reported for Safety Population which comprised of all participants who completed any study assessment.	0.00% 0/10 • Serious adverse events (SAEs) and non-serious adverse events (non-SAEs) were collected up to Day 14. SAEs and Non-SAEs were reported for Safety Population which comprised of all participants who completed any study assessment.
Injury, poisoning and procedural complications Post procedural contusion	33.3% 4/12 • Number of events 4 • Serious adverse events (SAEs) and non-serious adverse events (non-SAEs) were collected up to Day 14. SAEs and Non-SAEs were reported for Safety Population which comprised of all participants who completed any study assessment.	40.0% 4/10 • Number of events 4 • Serious adverse events (SAEs) and non-serious adverse events (non-SAEs) were collected up to Day 14. SAEs and Non-SAEs were reported for Safety Population which comprised of all participants who completed any study assessment.
Injury, poisoning and procedural complications Procedural pain	50.0% 6/12 • Number of events 6 • Serious adverse events (SAEs) and non-serious adverse events (non-SAEs) were collected up to Day 14. SAEs and Non-SAEs were reported for Safety Population which comprised of all participants who completed any study assessment.	40.0% 4/10 • Number of events 4 • Serious adverse events (SAEs) and non-serious adverse events (non-SAEs) were collected up to Day 14. SAEs and Non-SAEs were reported for Safety Population which comprised of all participants who completed any study assessment.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TFH cells; ; FNA; n=12, 8	24.09 Percenatge of total memory Conv T cells Standard Error 2.913	17.09 Percenatge of total memory Conv T cells Standard Error 3.651
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TFH cells; Core; n=11,10	21.94 Percenatge of total memory Conv T cells Standard Error 3.335	25.86 Percenatge of total memory Conv T cells Standard Error 3.491
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA PD-1+ ICOS+ TFH cells; FNA; n=8,4	0.89 Percenatge of total memory Conv T cells Standard Error 0.356	2.15 Percenatge of total memory Conv T cells Standard Error 0.545
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA PD-1+ ICOS+ TFH cells; Core; n=6,10	1.72 Percenatge of total memory Conv T cells Standard Error 1.239	1.71 Percenatge of total memory Conv T cells Standard Error 0.859
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH17 cells;FNA; n=12,8	7.73 Percenatge of total memory Conv T cells Standard Error 1.122	6.96 Percenatge of total memory Conv T cells Standard Error 1.289
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH17 cells; Core; n=11,10	5.38 Percenatge of total memory Conv T cells Standard Error 0.915	5.33 Percenatge of total memory Conv T cells Standard Error 0.977
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH1 cells; FNA; n=12,8	14.08 Percenatge of total memory Conv T cells Standard Error 2.340	15.05 Percenatge of total memory Conv T cells Standard Error 2.777
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH1 cells; Core; n=11,10	16.09 Percenatge of total memory Conv T cells Standard Error 1.858	22.12 Percenatge of total memory Conv T cells Standard Error 1.970
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH1 TH17 cells; FNA; n=10,4	2.97 Percenatge of total memory Conv T cells Standard Error 0.510	3.07 Percenatge of total memory Conv T cells Standard Error 0.728
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH1 TH17 cells; Core; n=10,10	3.08 Percenatge of total memory Conv T cells Standard Error 0.553	2.49 Percenatge of total memory Conv T cells Standard Error 0.559
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH1 TH17 TH2 T cells; FNA; n=10,4	1.87 Percenatge of total memory Conv T cells Standard Error 0.371	1.44 Percenatge of total memory Conv T cells Standard Error 0.488
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH1 TH17 TH2 T cells; Core; n=10,10	2.01 Percenatge of total memory Conv T cells Standard Error 0.390	1.63 Percenatge of total memory Conv T cells Standard Error 0.409
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH1 TH2 cells; FNA; n=12,6	6.20 Percenatge of total memory Conv T cells Standard Error 0.910	5.68 Percenatge of total memory Conv T cells Standard Error 1.250
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH1 TH2 cells; Core; n=10, 10	9.25 Percenatge of total memory Conv T cells Standard Error 1.130	8.83 Percenatge of total memory Conv T cells Standard Error 1.147
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH2 cells; FNA; n=12,8	20.82 Percenatge of total memory Conv T cells Standard Error 2.168	18.67 Percenatge of total memory Conv T cells Standard Error 2.562
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH2 cells; Core; n=11,10	19.24 Percenatge of total memory Conv T cells Standard Error 1.685	15.29 Percenatge of total memory Conv T cells Standard Error 1.821
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH22 cells; FNA; n=12,4	1.51 Percenatge of total memory Conv T cells Standard Error 0.336	1.46 Percenatge of total memory Conv T cells Standard Error 0.530
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH17 Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 T Cells, TH1 TH2 Cells, TH2 Cells, and TH22 Cells in iLN Core Biopsies and iLN FNA TH22 cells; Core; n=10, 10	1.49 Percenatge of total memory Conv T cells Standard Error 0.308	1.50 Percenatge of total memory Conv T cells Standard Error 0.311

Measure	Healthy Participants n=12 Participants Participants were considered healthy if values for the following parameters: fasted glucose, glycated hemoglobin, International normalized ratio (INR), activated partial thromboplastin time (APTT), platelet count, red blood cells and total lymphocyte count were within the normal range at screening.	Participants With NOT1D n=10 Participants NOT1D participants with documented diagnosis of diabetes mellitus according to American Diabetes Association (ADA) and World Health Organization (WHO) criteria and consistent with Type 1a (autoimmune) Diabetes Mellitus, were included in the study.
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TFH cells-like Reg T cells; FNA; n=11, 5	13.52 Percentage of total memory Reg T cells Standard Error 2.224	13.22 Percentage of total memory Reg T cells Standard Error 2.869
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TFH cells-like Reg T cells; Core; n=9, 10	13.44 Percentage of total memory Reg T cells Standard Error 1.884	12.71 Percentage of total memory Reg T cells Standard Error 1.926
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA PD-1+ ICOS+ TFH cells-like Reg T cells;FNA;n=2,3	NA Percentage of total memory Reg T cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.	NA Percentage of total memory Reg T cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA PD-1+ ICOS+ TFH cells-like Reg T cells;Core;n=4,5	NA Percentage of total memory Reg T cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.	NA Percentage of total memory Reg T cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH1 cells-like Reg T cells;FNA; n=11,5	7.19 Percentage of total memory Reg T cells Standard Error 1.428	12.09 Percentage of total memory Reg T cells Standard Error 1.900
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH1 cells-like Reg T cells;Core;n=8, 10	7.43 Percentage of total memory Reg T cells Standard Error 1.211	10.72 Percentage of total memory Reg T cells Standard Error 1.167
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH1 TH17-like Reg T cells;FNA; n=1, 1	NA Percentage of total memory Reg T cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.	NA Percentage of total memory Reg T cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH1 TH17-like Reg T cells;Core; n=0,2	—	NA Percentage of total memory Reg T cells Standard Error NA NA indicates that data was not available as the cell yield was too low to allow the analysis.
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH1 TH17 TH2 cells-like Reg T cells;FNA; n=7, 4	2.88 Percentage of total memory Reg T cells Standard Error 0.599	3.17 Percentage of total memory Reg T cells Standard Error 0.845
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH1 TH17 TH2 cells-like Reg T cells;Core;n=5,5	2.25 Percentage of total memory Reg T cells Standard Error 1.381	5.05 Percentage of total memory Reg T cells Standard Error 1.348
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH1 TH2 cells-like Reg T cells;FNA; n=11, 4	9.08 Percentage of total memory Reg T cells Standard Error 1.092	10.52 Percentage of total memory Reg T cells Standard Error 1.813
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH1 TH2 cells-like Reg T cells;Core; n=10,10	11.15 Percentage of total memory Reg T cells Standard Error 1.434	11.45 Percentage of total memory Reg T cells Standard Error 1.460
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH17 cells-like Reg T cells;FNA; n=11, 4	8.18 Percentage of total memory Reg T cells Standard Error 1.547	9.64 Percentage of total memory Reg T cells Standard Error 2.146
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH17 cells-like Reg T cells;Core; n=10, 10	6.23 Percentage of total memory Reg T cells Standard Error 1.507	5.70 Percentage of total memory Reg T cells Standard Error 1.582
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH2 cells-like Reg T cells;FNA; n=12, 8	27.38 Percentage of total memory Reg T cells Standard Error 2.749	29.63 Percentage of total memory Reg T cells Standard Error 3.305
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH2 cells-like Reg T cells;Core; n=11, 10	28.28 Percentage of total memory Reg T cells Standard Error 2.386	24.86 Percentage of total memory Reg T cells Standard Error 2.522
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH22 cells-like Reg T cells;FNA; n=6,3	2.30 Percentage of total memory Reg T cells Standard Error 0.653	2.95 Percentage of total memory Reg T cells Standard Error 0.950
Percentage of Leukocyte Subsets Including TFH Cells, PD-1+ ICOS+ TFH Cells, TH1 Cells, TH1 TH17 Cells, TH1 TH17 TH2 Cells, TH1 TH2 Cells, TH17 Cells, TH2 Cells and TH22 Cells-like Reg T Cells in iLN Core Biopsies and iLN FNA TH22 cells-like Reg T cells;Core; n=7,7	2.28 Percentage of total memory Reg T cells Standard Error 0.619	2.45 Percentage of total memory Reg T cells Standard Error 0.610