{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T20:27:03Z","timestamp":1790368023838,"version":"4.1.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>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).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:sub>FH<\/jats:sub>\n                      )-like memory and decrease of regulatory T cells in CVID-ILD BALF. This T\n                      <jats:sub>FH<\/jats:sub>\n                      -like cell subset is clearly skewed toward T\n                      <jats:sub>H<\/jats:sub>\n                      1 cells in CVID-ILD. In contrast to sarcoidosis, CVID-ILD BALF contains a higher percentage of B cells comprising mostly CD21\n                      <jats:sup>low<\/jats:sup>\n                      B cells, but less class-switched memory B cells. BALF analysis showed increased levels of APRIL, CXCL10, and IL-17.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Unlike in sarcoidosis, B cells are expanded in BALF of CVID-ILD patients. This is associated with an expansion of T\n                      <jats:sub>FH<\/jats:sub>\n                      - and T\n                      <jats:sub>PH<\/jats:sub>\n                      -like cells and an increase in APRIL potentially supporting B-cell survival and differentiation and proinflammatory cytokines reflecting not only the previously described T\n                      <jats:sub>H<\/jats:sub>\n                      1 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.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2020.616832","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T02:24:01Z","timestamp":1612491841000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":21,"title":["Bronchoalveolar Lavage Fluid Reflects a TH1-CD21low B-Cell Interaction in CVID-Related Interstitial Lung Disease"],"prefix":"10.3389","volume":"11","author":[{"given":"David","family":"Friedmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Unger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baerbel","family":"Keller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirzokhid","family":"Rakhmanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigune","family":"Goldacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gernot","family":"Zissel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn C.","family":"Frye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas C.","family":"Schupp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Prasse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Warnatz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.02.004","article-title":"The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical\u00a0Diagnosis of Inborn Errors of Immunity","volume":"7","author":"Seidel","year":"2019","journal-title":"J Allergy Clin Immunol Practice"},{"key":"B2","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jaip.2015.07.025","article-title":"International Consensus Document (ICON): Common Variable Immunodeficiency Disorders","volume":"4","author":"Bonilla","year":"2016","journal-title":"J Allergy Clin Immunol Practice"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2018.01.039","article-title":"Loss-of-function nuclear factor kappaB subunit 1 (NFKB1) variants are the most common monogenic cause of common variable immunodeficiency in Europeans","volume":"142","author":"Tuijnenburg","year":"2018","journal-title":"J Allergy Clin Immunol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.gendis.2019.10.002","article-title":"Recent advances in elucidating the genetics of common variable immunodeficiency","volume":"7","author":"Aggarwal","year":"2020","journal-title":"Genes Dis"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-007-9075-1","article-title":"Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency","volume":"27","author":"Quinti","year":"2007","journal-title":"J Clin Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1016\/j.jaci.2012.05.046","article-title":"Confirmation and improvement of criteria for clinical phenotyping in common variable immunodeficiency disorders in replicate cohorts","volume":"130","author":"Chapel","year":"2012","journal-title":"J Allergy Clin Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-11-124545","article-title":"Common variable immunodeficiency disorders: division into distinct clinical phenotypes","volume":"112","author":"Chapel","year":"2008","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-09-377945","article-title":"Morbidity and mortality in common variable immune deficiency over 4 decades","volume":"119","author":"Resnick","year":"2012","journal-title":"Blood"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-017-0404-8","article-title":"Health-Related Quality of Life in Adult Patients with Common Variable Immunodeficiency Disorders and Impact of Treatment","volume":"37","author":"Rider","year":"2017","journal-title":"J Clin Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/cei.13252","article-title":"Perceived health of patients with common variable immunodeficiency - 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