Related Experiment Video
Updated: Nov 16, 2025
Bronchoalveolar Lavage of Murine Lungs to Analyze Inflammatory Cell Infiltration
Published on: May 4, 2017
Bronchoalveolar Lavage Fluid Reflects a TH1-CD21low B-Cell Interaction in CVID-Related Interstitial Lung Disease
David Friedmann1,2,3, Susanne Unger1,2,4, Baerbel Keller1,2
1Divison of Immunodeficiency, Department of Rheumatology and Clinical Immunology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Insights
Bronchoalveolar lavage (BAL) analysis reveals expanded B cells and specific T-cell subsets in common variable immunodeficiency with interstitial lung disease (CVID-ILD). These findings suggest BAL fluid can diagnose CVID-ILD and guide B-cell targeted treatments.
Area of Science:
- Immunology
- Pulmonology
- Cell Biology
Background:
- Common variable immunodeficiency (CVID) is associated with interstitial lung disease (ILD) in 20% of patients, suggesting immune dysregulation.
- B cells are implicated in CVID-ILD pathogenesis, with elevated BAFF and IgM levels observed in active disease.
- The diagnostic utility of less invasive methods like bronchoalveolar lavage (BAL) for CVID-ILD is under investigation, contrasting with current biopsy-based approaches.
Purpose of the Study:
- To investigate immune mechanisms in granulomatous and lymphocytic interstitial lung disease (GLILD) within CVID-ILD.
- To identify biomarkers for progressive ILD by analyzing B- and T-cell phenotypes and cytokine profiles in BAL fluid.
- To compare BAL fluid characteristics in CVID-ILD patients with sarcoidosis patients and healthy donors.
Main Methods:
- Analysis of BAL fluid from 64 CVID-ILD patients, 6 sarcoidosis patients, and 25 healthy donors.
- Flow cytometric profiling to characterize B- and T-cell populations.
- Cytokine analysis using ELISA and Multiplexing LASER Bead technology.
Main Results:
- CVID-ILD and sarcoidosis BAL fluid show T-cell lymphocytosis; CVID-ILD exhibits increased T follicular helper (TFH)-like cells and decreased regulatory T cells, skewed towards TH1.
- CVID-ILD BAL fluid has a higher percentage of B cells, including CD21low B cells, but fewer class-switched memory B cells compared to sarcoidosis.
- Elevated levels of APRIL, CXCL10, and IL-17 were detected in CVID-ILD BAL fluid.
Conclusions:
- BAL fluid analysis reveals expanded B cells and specific T-cell populations in CVID-ILD, distinct from sarcoidosis.
- Increased APRIL in BALF may promote B-cell survival and differentiation, contributing to CVID-ILD pathogenesis.
- BAL fluid analysis holds diagnostic value for CVID-ILD activity and can inform B-cell targeted treatment strategies.
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 (TFH)-like memory and decrease of regulatory T cells in CVID-ILD BALF. This TFH-like cell subset is clearly skewed toward TH1 cells in CVID-ILD. In contrast to sarcoidosis, CVID-ILD BALF contains a higher percentage of B cells comprising mostly CD21low 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 TFH- and TPH-like cells and an increase in APRIL potentially supporting B-cell survival and differentiation and proinflammatory cytokines reflecting not only the previously described TH1 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.
