Dataset Information

Bronchoalveolar Lavage Fluid Reflects a T_H1-CD21^low B-Cell Interaction in CVID-Related Interstitial Lung Disease.

ABSTRACT:

Background

About 20% of patients with common variable immunodeficiency (CVID) suffer from interstitial lung disease (ILD) as part of a systemic immune dysregulation. Current understanding suggests a role of B cells in the pathogenesis based on histology and increased levels of BAFF and IgM associated with active disease corroborated by several reports which demonstrate the successful use of rituximab in CVID-ILD. It is debated whether histological confirmation by biopsy or even video-assisted thoracoscopy is required and currently not investigated whether less invasive methods like a bronchoalveolar lavage (BAL) might provide an informative diagnostic tool.

Objective

To gain insight into potential immune mechanisms underlying granulomatous and lymphocytic interstitial lung disease (GLILD) and to define biomarkers for progressive ILD by characterizing the phenotype of B- and T-cell populations and cytokine profiles in BAL fluid (BALF) of CVID-ILD compared to sarcoidosis patients and healthy donors (HD).

Methods

Sixty-four CVID, six sarcoidosis, and 25 HD BALF samples were analyzed by flow cytometric profiling of B- and T-cells and for cytokines by ELISA and Multiplexing LASER Bead technology.

Results

Both sarcoidosis and CVID-ILD are characterized by a predominantly T-cell mediated lymphocytosis in the BALF. There is an increase in T follicular helper (T_FH)-like memory and decrease of regulatory T cells in CVID-ILD BALF. This T_FH-like cell subset is clearly skewed toward T_H1 cells in CVID-ILD. In contrast to sarcoidosis, CVID-ILD BALF contains a higher percentage of B cells comprising mostly CD21^low B cells, but less class-switched memory B cells. BALF analysis showed increased levels of APRIL, CXCL10, and IL-17.

Conclusion

Unlike in sarcoidosis, B cells are expanded in BALF of CVID-ILD patients. This is associated with an expansion of T_FH- and T_PH-like cells and an increase in APRIL potentially supporting B-cell survival and differentiation and proinflammatory cytokines reflecting not only the previously described T_H1 profile seen in CVID patients with secondary immune dysregulation. Thus, the analysis of BALF might be of diagnostic value not only in the diagnosis of CVID-ILD, but also in the evaluation of the activity of the disease and in determining potential treatment targets confirming the prominent role of B-cell targeted strategies.

SUBMITTER: Friedmann D

PROVIDER: S-EPMC7892466 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Bronchoalveolar Lavage Fluid Reflects a T<sub>H</sub>1-CD21<sup>low</sup> B-Cell Interaction in CVID-Related Interstitial Lung Disease.

Friedmann David D Unger Susanne S Keller Baerbel B Rakhmanov Mirzokhid M Goldacker Sigune S Zissel Gernot G Frye Björn C BC Schupp Jonas C JC Prasse Antje A Warnatz Klaus K

Frontiers in immunology 20210205

<h4>Background</h4>About 20% of patients with common variable immunodeficiency (CVID) suffer from interstitial lung disease (ILD) as part of a systemic immune dysregulation. Current understanding suggests a role of B cells in the pathogenesis based on histology and increased levels of BAFF and IgM associated with active disease corroborated by several reports which demonstrate the successful use of rituximab in CVID-ILD. It is debated whether histological confirmation by biopsy or even video-ass ...[more]

PMID: 33613543

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Dataset Information

Bronchoalveolar Lavage Fluid Reflects a T_H1-CD21^low B-Cell Interaction in CVID-Related Interstitial Lung Disease.

Background

Objective

Methods

Results

Conclusion

Publications

Bronchoalveolar Lavage Fluid Reflects a T<sub>H</sub>1-CD21<sup>low</sup> B-Cell Interaction in CVID-Related Interstitial Lung Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Bronchoalveolar Lavage Fluid Reflects a TH1-CD21low B-Cell Interaction in CVID-Related Interstitial Lung Disease.

Background

Objective

Methods

Results

Conclusion

Publications

Bronchoalveolar Lavage Fluid Reflects a T<sub>H</sub>1-CD21<sup>low</sup> B-Cell Interaction in CVID-Related Interstitial Lung Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Bronchoalveolar Lavage Fluid Reflects a T_H1-CD21^low B-Cell Interaction in CVID-Related Interstitial Lung Disease.