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We have previously shown that circulating bacterial 16S ribosomal DNA (rDNA), originating from gut commensals, is significantly increased in the serum of patients with CVID with inflammatory conditions (P = 0.0007). Here we examined the relationships between serum 16S ribosomal DNA (rDNA), isotype-switched memory (SM) B cells, serum IgA, IgA+ SM B cells, serum IFN-\u03b3, and serum B cell\u2013activating factor (BAFF). We found a significant inverse correlation between serum 16S ribosomal DNA (rDNA) concentrations and the numbers of isotype SM B cells, IgA+ SM B cells, and serum IgA levels in our large cohort, suggesting that loss of IgA in the mucosal barrier permits bacterial transcytosis. Loss of SM B cells and lower serum IgA concentrations were both associated with increased serum IFN-\u03b3, as well as increased CXCL9 and serum BAFF concentrations. Serum BAFF was also significantly associated with IFN-\u03b3 levels and inversely correlated with baseline serum IgA. We conclude that loss of IgA, accompanied by mucosal defects in CVID, may permit bacterial transcytosis, resulting in excessive IFN-\u03b3 and BAFF production, both of which promote autoimmune and inflammatory complications in this immune defect.<\/jats:p>","DOI":"10.70962\/jhi.20250080","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T07:21:45Z","timestamp":1766128905000},"update-policy":"https:\/\/doi.org\/10.70962\/jhi.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["IgA defects in CVID lead to bacterial translocation, increased serum \u03b3-interferon, and BAFF"],"prefix":"10.70962","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7160-2960","authenticated-orcid":true,"given":"Hsi-en","family":"Ho","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04a9tmd77","id-type":"ROR","asserted-by":"publisher"}],"name":"Icahn School of Medicine at Mount Sinai 1 Department of Medicine, , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4929-1613","authenticated-orcid":true,"given":"Lin","family":"Radigan","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04a9tmd77","id-type":"ROR","asserted-by":"publisher"}],"name":"Icahn School of Medicine at Mount Sinai 1 Department of Medicine, , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4326-0171","authenticated-orcid":true,"given":"Eric","family":"Meffre","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine 2 Division of Immunology and Rheumatology, Department of Medicine, , Stanford, CA,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0725-0320","authenticated-orcid":true,"given":"Charlotte","family":"Cunningham-Rundles","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04a9tmd77","id-type":"ROR","asserted-by":"publisher"}],"name":"Icahn School of Medicine at Mount Sinai 1 Department of Medicine, , New York, NY,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,1,13]]},"reference":[{"key":"2026011311142980700_bib1","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. 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