Associations of serum and bronchoalveolar immunoglobulins with lung microbiota diversity, B-cell memory phenotypes, and COPD morbidity and exacerbations
Abstract Rationale Immunoglobulins (Ig) protect against pathogens frequently implicated in COPD exacerbations. We previously demonstrated an association of low-normal serum IgA and IgG concentrations with prospective exacerbation risk, but responsible mechanisms are undefined. Here, we examined asso...
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2025-07-01
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| Series: | Respiratory Research |
| Online Access: | https://doi.org/10.1186/s12931-025-03310-w |
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| author | Vickram Tejwani Nirupama Putcha Han Woo Chen Liu David Lafon Neil E. Alexis Antoine Azar R. Graham Barr Igor Barjaktarevic Russell P. Bowler Alejandro Comellas David J. Couper Ashraf Fawzy MeiLan K. Han Nadia N. Hansel Robert J. Kaner Jerry A. Krishnan Nathaniel Marchetti Fernando J. Martinez Jill Ohar Wanda O’Neal Victor E. Ortega Robert Paine III Tess D. Pottinger Martin Stämpfli Lisa Ruvuna Prescott G. Woodruff Christine M. Freeman Yvonne J. Huang Jeffrey L. Curtis |
| author_facet | Vickram Tejwani Nirupama Putcha Han Woo Chen Liu David Lafon Neil E. Alexis Antoine Azar R. Graham Barr Igor Barjaktarevic Russell P. Bowler Alejandro Comellas David J. Couper Ashraf Fawzy MeiLan K. Han Nadia N. Hansel Robert J. Kaner Jerry A. Krishnan Nathaniel Marchetti Fernando J. Martinez Jill Ohar Wanda O’Neal Victor E. Ortega Robert Paine III Tess D. Pottinger Martin Stämpfli Lisa Ruvuna Prescott G. Woodruff Christine M. Freeman Yvonne J. Huang Jeffrey L. Curtis |
| author_sort | Vickram Tejwani |
| collection | DOAJ |
| description | Abstract Rationale Immunoglobulins (Ig) protect against pathogens frequently implicated in COPD exacerbations. We previously demonstrated an association of low-normal serum IgA and IgG concentrations with prospective exacerbation risk, but responsible mechanisms are undefined. Here, we examined associations of lower respiratory tract bacterial diversity to Ig levels in serum and bronchoalveolar lavage (BAL) and to the memory phenotypes of blood and BAL B cells. Methods We analyzed data from phase I of SPIROMICS, an observational cohort study of smoking-related COPD. A subset of participants completed comprehensive research bronchoscopies, including analysis of BAL bacterial microbiota by 16 S rRNA gene (V4 region) sequencing and of blood and BAL B-cells by 12-color flow cytometry. In some participants, we also analyzed serum and BAL Ig levels by ELISA. We constructed linear regression models including either serum or BAL (albumin-corrected) Ig measurements as the independent variable and separate dependent variables, including B-cell subsets, BAL bacterial diversity metrics (Faith phylogenetic diversity, inverse Simpson, and richness indices), and clinical measures (FEV1% predicted, risk of prospective exacerbations), adjusted by age, sex, race, educational attainment, smoking status, and use of inhaled corticosteroids. Results Serum IgG and IgA (n = 66 participants) were 1,486.1 ± 510.6 mg/dL [mean ± standard deviation (SD)] and 237.7 ± 131.6 mg/dL, respectively. Albumin-corrected BAL IgG and IgA (n = 117) were 0.03 ± 0.02 mg/dL and 0.01 ± 0.01 mg/dL, respectively. B-cells (n = 82) comprised 3.5 ± 3.0% of blood leukocytes. Serum IgA was associated with higher blood switched memory (IgD- CD27+) B-cell percentages (β 6.06, p = 0.01) and inversely associated with blood double-negative (IgD-CD27-) B-cell percentages (β − 9.96, p = 0.02). Available BAL microbiome data (n = 107) showed that reduced lung bacterial diversity associated with lower serum IgG, but not with serum IgA, BAL IgA, or BAL IgG concentrations. Neither BAL IgG nor IgA were associated with lung function or exacerbations. Conclusions These results demonstrate an association of low serum IgG with reduced lung bacterial diversity, a feature of dysbiosis that may predispose to exacerbation. Defining the role of Ig in specific anatomic compartments is relevant to designing vaccine strategies. |
| format | Article |
| id | doaj-art-5a94cc3720804eafb83736e16a1646df |
| institution | Kabale University |
| issn | 1465-993X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj-art-5a94cc3720804eafb83736e16a1646df2025-08-20T04:03:02ZengBMCRespiratory Research1465-993X2025-07-012611810.1186/s12931-025-03310-wAssociations of serum and bronchoalveolar immunoglobulins with lung microbiota diversity, B-cell memory phenotypes, and COPD morbidity and exacerbationsVickram Tejwani0Nirupama Putcha1Han Woo2Chen Liu3David Lafon4Neil E. Alexis5Antoine Azar6R. Graham Barr7Igor Barjaktarevic8Russell P. Bowler9Alejandro Comellas10David J. Couper11Ashraf Fawzy12MeiLan K. Han13Nadia N. Hansel14Robert J. Kaner15Jerry A. Krishnan16Nathaniel Marchetti17Fernando J. Martinez18Jill Ohar19Wanda O’Neal20Victor E. Ortega21Robert Paine III22Tess D. Pottinger23Martin Stämpfli24Lisa Ruvuna25Prescott G. Woodruff26Christine M. Freeman27Yvonne J. Huang28Jeffrey L. Curtis29Department of Pulmonary and Critical Care Medicine, Integrated Hospital Care Institute, Cleveland ClinicDivision of Pulmonary and Critical Care Medicine, Johns Hopkins UniversityDivision of Pulmonary and Critical Care Medicine, Johns Hopkins UniversityDivision of Pulmonary and Critical Care Medicine, Johns Hopkins UniversityDivision of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at BirminghamDivision of Allergy, Immunology and Infectious Disease, Department of Pediatrics, School of Medicine, University of North Carolina at Chapel HillDivision of Allergy and Immunology, Johns Hopkins UniversityDepartment of Medicine, Columbia University College of Physicians and SurgeonsDivision of Pulmonary and Critical Care Medicine, University of California Los Angeles Medical CenterDepartment of Pulmonary and Critical Care Medicine, Integrated Hospital Care Institute, Cleveland ClinicDivision of Pulmonary, Critical Care, and Occupational Medicine, College of Medicine, University of IowaDepartment of Biostatistics, Gillings School of Global Public HealthDivision of Pulmonary and Critical Care Medicine, Johns Hopkins UniversityDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Michigan MedicineDivision of Pulmonary and Critical Care Medicine, Johns Hopkins UniversityDepartments of Medicine and Genomic Medicine, Weill-Cornell College of MedicineChicago Center, Division of Pulmonary, Critical Care, Sleep, and Allergy, University of Illinois ChicagoDepartment of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple UniversityDivision of Pulmonary and Critical Care Medicine, University of MassachusettsSection of Pulmonary, Critical Care, Allergy and Immunologic Diseases, Wake Forest UniversityMarsico Lung Institute, University of North Carolina at Chapel HillDivision of Pulmonary and Critical Care Medicine, Mayo ClinicDivision of Respiratory, Critical Care, and Occupational Pulmonary Medicine, University of Utah School of MedicineDepartment of Medicine, Columbia University College of Physicians and SurgeonsCentre for Gene Therapeutics, CSL BehringDepartment of Pulmonary and Critical Care Medicine, Integrated Hospital Care Institute, Cleveland ClinicDivision of Pulmonary, Critical Care and Sleep Medicine, University of California San FranciscoDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Michigan MedicineDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Michigan MedicineDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Michigan MedicineAbstract Rationale Immunoglobulins (Ig) protect against pathogens frequently implicated in COPD exacerbations. We previously demonstrated an association of low-normal serum IgA and IgG concentrations with prospective exacerbation risk, but responsible mechanisms are undefined. Here, we examined associations of lower respiratory tract bacterial diversity to Ig levels in serum and bronchoalveolar lavage (BAL) and to the memory phenotypes of blood and BAL B cells. Methods We analyzed data from phase I of SPIROMICS, an observational cohort study of smoking-related COPD. A subset of participants completed comprehensive research bronchoscopies, including analysis of BAL bacterial microbiota by 16 S rRNA gene (V4 region) sequencing and of blood and BAL B-cells by 12-color flow cytometry. In some participants, we also analyzed serum and BAL Ig levels by ELISA. We constructed linear regression models including either serum or BAL (albumin-corrected) Ig measurements as the independent variable and separate dependent variables, including B-cell subsets, BAL bacterial diversity metrics (Faith phylogenetic diversity, inverse Simpson, and richness indices), and clinical measures (FEV1% predicted, risk of prospective exacerbations), adjusted by age, sex, race, educational attainment, smoking status, and use of inhaled corticosteroids. Results Serum IgG and IgA (n = 66 participants) were 1,486.1 ± 510.6 mg/dL [mean ± standard deviation (SD)] and 237.7 ± 131.6 mg/dL, respectively. Albumin-corrected BAL IgG and IgA (n = 117) were 0.03 ± 0.02 mg/dL and 0.01 ± 0.01 mg/dL, respectively. B-cells (n = 82) comprised 3.5 ± 3.0% of blood leukocytes. Serum IgA was associated with higher blood switched memory (IgD- CD27+) B-cell percentages (β 6.06, p = 0.01) and inversely associated with blood double-negative (IgD-CD27-) B-cell percentages (β − 9.96, p = 0.02). Available BAL microbiome data (n = 107) showed that reduced lung bacterial diversity associated with lower serum IgG, but not with serum IgA, BAL IgA, or BAL IgG concentrations. Neither BAL IgG nor IgA were associated with lung function or exacerbations. Conclusions These results demonstrate an association of low serum IgG with reduced lung bacterial diversity, a feature of dysbiosis that may predispose to exacerbation. Defining the role of Ig in specific anatomic compartments is relevant to designing vaccine strategies.https://doi.org/10.1186/s12931-025-03310-w |
| spellingShingle | Vickram Tejwani Nirupama Putcha Han Woo Chen Liu David Lafon Neil E. Alexis Antoine Azar R. Graham Barr Igor Barjaktarevic Russell P. Bowler Alejandro Comellas David J. Couper Ashraf Fawzy MeiLan K. Han Nadia N. Hansel Robert J. Kaner Jerry A. Krishnan Nathaniel Marchetti Fernando J. Martinez Jill Ohar Wanda O’Neal Victor E. Ortega Robert Paine III Tess D. Pottinger Martin Stämpfli Lisa Ruvuna Prescott G. Woodruff Christine M. Freeman Yvonne J. Huang Jeffrey L. Curtis Associations of serum and bronchoalveolar immunoglobulins with lung microbiota diversity, B-cell memory phenotypes, and COPD morbidity and exacerbations Respiratory Research |
| title | Associations of serum and bronchoalveolar immunoglobulins with lung microbiota diversity, B-cell memory phenotypes, and COPD morbidity and exacerbations |
| title_full | Associations of serum and bronchoalveolar immunoglobulins with lung microbiota diversity, B-cell memory phenotypes, and COPD morbidity and exacerbations |
| title_fullStr | Associations of serum and bronchoalveolar immunoglobulins with lung microbiota diversity, B-cell memory phenotypes, and COPD morbidity and exacerbations |
| title_full_unstemmed | Associations of serum and bronchoalveolar immunoglobulins with lung microbiota diversity, B-cell memory phenotypes, and COPD morbidity and exacerbations |
| title_short | Associations of serum and bronchoalveolar immunoglobulins with lung microbiota diversity, B-cell memory phenotypes, and COPD morbidity and exacerbations |
| title_sort | associations of serum and bronchoalveolar immunoglobulins with lung microbiota diversity b cell memory phenotypes and copd morbidity and exacerbations |
| url | https://doi.org/10.1186/s12931-025-03310-w |
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