{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T08:13:31Z","timestamp":1773389611655,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Common Variable Immunodeficiency (CVID) is a heterogeneous immune disorder characterized by a broad range of clinical manifestations. Its etiology is not yet fully understood. To gain insights into the immunological background of CVID in patients without a clearly defined genetic cause, we\u00a0employed a genealogical research approach that included family members. This strategy aims to provide a more comprehensive understanding of immune dysregulation in CVID, of potential hereditary patterns, and subclinical immunological traits within families.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Fifty-eight participants from nine families were included: Five families with a negative family history for CVID (FH-) and four families with a positive family history for CVID (FH+). Screening for known CVID-associated genes was negative in all cases. The non-affected family members completed a questionnaire covering medical history relevant to primary immunodeficiency. Flow cytometry was used to analyze T- and B-cell subsets in peripheral blood, while\u00a0mucosal and systemic IgA and IgG levels were measured using a multiplex immunoassay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Immune aberrancies in CVID patients were observed in the B- and T-cell compartments. In both FH\u2212 and FH+ family members, symptoms suggestive of Primary Immunodeficiency (PID) were present in 32.1 to 61.5% (p = 0.29). B-cell subsets were 5- to 10-fold reduced compared with the 5th percentile of age specific reference values. A combination of T-cell and B-cell reductions was observed in eight of the nine families in a non-affected member. Serum and mucosal IgG and IgA levels in FH\u2212 families did not differ significantly from FH+ families. There were no significant correlations between systemic and mucosal IgA levels in non-affected family members from either FH- or FH+ families.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, our findings show that B- and T-cell aberrancies are present not only in CVID patients but also in non-affected family members, irrespective of family history. Systemic IgA does not reflect mucosal IgA, and systemic IgG replacement therapy does not restore mucosal antibody levels, highlighting compartmentalized immune regulation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1741900","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T05:25:52Z","timestamp":1773379552000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Familial patterns of immune dysregulation in CVID: insights from B- and T-cell phenotyping and antibody profiling"],"prefix":"10.3389","volume":"17","author":[{"given":"Suzanne E. T.","family":"Comans","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud Community for Infectious Diseases","place":["Radboud university medical center, Nijmegen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelien G. G.","family":"Sprenkeler","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud Community for Infectious Diseases","place":["Radboud university medical center, Nijmegen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mischa H.","family":"Koenen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Erasmus Medical Center","place":["Rotterdam, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elles","family":"Simonetti","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud Community for Infectious Diseases","place":["Radboud university medical center, Nijmegen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bram","family":"Van Cranenbroek","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud Community for Infectious Diseases","place":["Radboud university medical center, Nijmegen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Van Rijssen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud Community for Infectious Diseases","place":["Radboud university medical center, Nijmegen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riet","family":"Strik-Albers","sequence":"additional","affiliation":[{"name":"Department of Pediatric Infectious Diseases and Immunology, Amalia Children\u2019s Hospital","place":["Radboud university medical center, Nijmegen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans J. P. M.","family":"Koenen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud Community for Infectious Diseases","place":["Radboud university medical center, Nijmegen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques J. M.","family":"van Dongen","sequence":"additional","affiliation":[{"name":"Cytometry Service, NUCLEUS; Department of Medicine, University of Salamanca (Universidad de Salamanca)","place":["Salamanca, Spain"]},{"name":"Translational and Clinical Research Program, Cancer Research Center (IBMCC, CSIC - University of Salamanca)","place":["Salamanca, Spain"]},{"name":"Department of Immunology, Leiden University Medical Center","place":["Leiden, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilly M.","family":"Verhagen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud Community for Infectious Diseases","place":["Radboud university medical center, Nijmegen, Netherlands"]},{"name":"Department of Pediatric Infectious Diseases and Immunology, Amalia Children\u2019s Hospital","place":["Radboud university medical center, Nijmegen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marien I.","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud Community for Infectious Diseases","place":["Radboud university medical center, Nijmegen, Netherlands"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie S. 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