Alterations in CD8αβ and CD8αα T Cell Levels in Patients With Rheumatoid Arthritis

NCT ID: NCT05827562

Last Updated: 2023-04-25

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-11-01
• Study Completion Date: 2025-12-31

Brief Summary

To evaluate the changes in the frequencies of circulating CD4+ and CD4- T cells expressing CD8αα and CD8αβ in peripheral blood of RA patients in comparison with healthy controls. Also, to correlate circulating and synovial fluid levels of these cells with disease activity score (DAS28) and other indices of disease severity.

Detailed Description

Rheumatoid arthritis (RA) is a chronic, inflammatory, systemic autoimmune disease of the joints . CD4+ T cells are predominant in the synovial tissue with increased number of CD8 effector and memory T cells in synovial fluid and tissue of RA patients . CD8 functions as a dimer; including homodimer CD8αα and heterodimer CD8αβ . CD8αβ is a superior T-cell co-receptor that enhances functional avidity, CD8αα functions as a TCR corepressor to negatively regulate T cell activation . CD8αα T cells are found in human intestine and peripheral blood . CD8αα T cells increased markedly in the lesions of psoriasis where they played a pro-inflammatory role . The lower percentage of CD8αα+ mucosa associated-invariant T (MAIT) cells was found to be associated with MAIT cell dysfunction in gut immunity in necrotizing enterocolitis patients . T cells express the CD8β chain either at a high (CD8βhigh) or low density (CD8βlow ). There was a relative increase in CD8βlow cells in patients with SLE which were associated with an increased disease activity . Double positive (DP) T lymphocytes, include CD4CD8αβhigh and CD4CD8αα T cell subsets in the human blood . DP8α cells decreased in the blood and colonic mucosa of patients with inflammatory bowel disease compared with healthy individuals . CD4CD8αβhigh T cells are present at higher frequencies in some auto-immune diseases . Whether CD8αα or CD8αβ T cells contribute to the pathogenesis of RA, has not been clarified so far. investigators hypothesize that, an alteration in the frequency and distribution of these T cell subsets in RA patients might be associated with disease activity

Conditions

Rheumatoid Arthritis

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: RETROSPECTIVE

Study Groups

patients group

. Inclusion criteria:

• Patients with RA who fulfilled the 2010 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) revised criteria for RA (1
• Patients having knee effusion .

Exclusion criteria:

• Patients with autoimmune diseases other than RA.
• Patients or controls with tumors, infections, or other severe organ damage.

flow cytometry

Intervention Type: DIAGNOSTIC_TEST

Levels of circulating and synovial fluid CD4+ and CD4- T cells expressing CD8αα and CD8αβ will be assessed by flow cytometry using fluorochrome-labelled monoclonal antibodies against CD3, CD4, CD8α and CD8β surface markers. Levels of the following cells will be assessed:

1. CD3+CD4-CD8αα+

2. CD3+CD4-CD8α+CD8βlow

3. CD3+CD4-CD8α+CD8βhigh

4. CD3+CD4+CD8αβhigh

5. CD3+CD4+CD8αα+

controls group

healthy subjects

flow cytometry

Intervention Type: DIAGNOSTIC_TEST

Levels of circulating and synovial fluid CD4+ and CD4- T cells expressing CD8αα and CD8αβ will be assessed by flow cytometry using fluorochrome-labelled monoclonal antibodies against CD3, CD4, CD8α and CD8β surface markers. Levels of the following cells will be assessed:

1. CD3+CD4-CD8αα+

2. CD3+CD4-CD8α+CD8βlow

3. CD3+CD4-CD8α+CD8βhigh

4. CD3+CD4+CD8αβhigh

5. CD3+CD4+CD8αα+

Interventions

flow cytometry

Levels of circulating and synovial fluid CD4+ and CD4- T cells expressing CD8αα and CD8αβ will be assessed by flow cytometry using fluorochrome-labelled monoclonal antibodies against CD3, CD4, CD8α and CD8β surface markers. Levels of the following cells will be assessed:

1. CD3+CD4-CD8αα+

2. CD3+CD4-CD8α+CD8βlow

3. CD3+CD4-CD8α+CD8βhigh

4. CD3+CD4+CD8αβhigh

5. CD3+CD4+CD8αα+

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Patients with RA who fulfilled the 2010 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) revised criteria for RA (12).

Patients having knee effusion .

Exclusion Criteria

• Patients with autoimmune diseases other than RA. Patients or controls with tumors, infections, or other severe organ damage.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Assiut University

OTHER

Sponsor Role: lead

Responsible Party

Hager Ahmed Ibrahim Mohammad

principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Central Contacts

Hager Mohammad, Demonstrator

Role: CONTACT

hager222.eg@gmail.com

01144867843

Omnia El-Badawy, Assistant Professor

Role: CONTACT

omniaalbadawy@aun.edu.eg

01005212176

References

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Reference Type: BACKGROUND

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Sarrabayrouse G, Bossard C, Chauvin JM, Jarry A, Meurette G, Quevrain E, Bridonneau C, Preisser L, Asehnoune K, Labarriere N, Altare F, Sokol H, Jotereau F. CD4CD8alphaalpha lymphocytes, a novel human regulatory T cell subset induced by colonic bacteria and deficient in patients with inflammatory bowel disease. PLoS Biol. 2014 Apr 8;12(4):e1001833. doi: 10.1371/journal.pbio.1001833. eCollection 2014 Apr.

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Other Identifiers

T cells in RA

Identifier Type: -

Identifier Source: org_study_id