The Role of JAK2 in Alveolar Macrophages (AM's) in Chronic Beryllium Disease (CBD)

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

3 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-04-30

Study Completion Date

2019-12-06

Brief Summary

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Current studies suggest that alveolar macrophages (AM) act as silencers of most immune responses in the lung. However, in pathological conditions, such as asthma, hypersensitivity pneumonitis, and sarcoidosis, AMs become involved in the maintenance and further expansion of the immune response in the target organ. The Investigator has preliminary data demonstrating that CBD AMs at the site of disease involvement (bronchoalveolar lavage, BAL) display an activated cell surface phenotype compared to AMs from healthy controls. Furthermore, exciting data from our group demonstrates significant differences in gene expression profiles between CBD and Beryllium Sensitivity (BeS) bronchial alveolar lavage (BAL) cells, in pivotal immune response genes and networks. Specifically, the Investigator has found the JAK/STAT pathway and the JAK2 gene was dramatically overexpressed in CBD BAL cells. In addition, constitutively phosphorylated JAK2 (pJAK2) was found in AMs from Chronic Beryllium Disease (CBD) patients by Westernblot and was increased after beryllium (Be) stimulation for 30 min. Moreover, the JAK2 inhibitor TG101348 significantly inhibited Be-induced CBD AMs TNFa and IFNy production. Meanwhile, overexpression of the JAK2 inhibitor SOCS 1 (suppressors of cytokine signaling) protein decreased Be-induced TNFa production from AMs. Based on this information, the Investigator hypothesizes that CBD AMs overexpress JAK2, which augments the immune response to Be and development of CBD but not BeS.

The investigators believe that these studies are highly innovative since they will undoubtedly shed light on exposure-mediated immune dysregulation in Alveolar Macrophages (AMs) that lead to disease development and likely progression and with additional study of this pathway will reveal potential biomarkers for clinical prognosis and diagnosis. The results obtained from this study will improve the investigators understanding of factors involved in the development of Chronic Beryllium disease (CBD), as well as define targets for therapy, and will serve as a model of other exposure-related immune responses and environmentally-induced chronic diseases. Most importantly, these studies will provide the investigator with preliminary data to submit a high quality R01, allowing the Investigator to apply similar approaches to other genes, define a potential target for this and other similar immune-mediated diseases and continue research efforts at National Jewish Health (NJH.)

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Detailed Description

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Conditions

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Chronic Beryllium Disease (CBD) Beryllium Sensitization (BeS)

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

CROSS_SECTIONAL

Study Groups

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Beryllium Sensitization (BeS)

Blood draw

Intervention Type PROCEDURE

We will draw 4 heparin tubes for peripheral blood mononuclear cells (PBMC)

Chronic Beryllium Disease(CBD)

blood draw BAL

Blood draw

Intervention Type PROCEDURE

We will draw 4 heparin tubes for peripheral blood mononuclear cells (PBMC)

bronchoscopy

Intervention Type PROCEDURE

CBD subjects will undergo a bronchoscopy with lavage. This is the passage of a think flexible tube through the nose into the windpipe then into the bronchial tubes. Sterile saltwater solution is through the flexible tube then immediately removed.

Interventions

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Blood draw

We will draw 4 heparin tubes for peripheral blood mononuclear cells (PBMC)

Intervention Type PROCEDURE

bronchoscopy

CBD subjects will undergo a bronchoscopy with lavage. This is the passage of a think flexible tube through the nose into the windpipe then into the bronchial tubes. Sterile saltwater solution is through the flexible tube then immediately removed.

Intervention Type PROCEDURE

Other Intervention Names

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BAL

Eligibility Criteria

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Inclusion Criteria

1. History of beryllium exposure;
2. Positive blood and/or bronchoalveolar lavage (BAL) Beryllium Lymphocyte Proliferation Tests (BeLPT);
3. Biopsy-proven pathologic changes consistent with CBD, specifically non-caseating granulomas and/or mononuclear cell interstitial infiltrates .

1. History of beryllium exposure;
2. Two or more positive blood beryllium lymphocyte proliferation tests (BeLPT) or positive bronchoalveolar lavage (BAL) BeLPT;
3. Normal lung tissue (no histology suggestive of CBD).