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Low prevalence and sporadic reporting have limited investigative efforts. We conducted a prospective, multimodal, study to establish the GS phenotype in the absence of severe infections. A previously characterized cohort of GS patients was compared to healthy individuals and those diagnosed with CVID or XLA using serology, immunophenotyping and histopathology. We also attempted to establish an inborn cause of the immune deficiency with HLA typing and Whole Exome Sequencing. GS patients exhibited severe hypogammaglobulinemia, a complete absence of B-cells in the peripheral blood and in biopsied primary and secondary lymphoid tissues. Total lymphocytes and CD4 T-cell counts were markedly reduced in GS but with intact T-cell proliferative capacity to in vitro mitogen and lectin stimulation. Autoantibody profiling identified high titers of antibodies in GS patient plasma to several cytokines, notably anti-interferons, which persisted for several years. These antibodies overlapped with those observed in thymoma patients without GS. We demonstrate that GS involves profound B-cell-loss, extending beyond blood to the lymphoid tissue, however plasma cells and circulating anti-cytokine antibodies can persist for years. In the absence of a unifying monogenic defect, the findings are suggestive of a thymoma-associated breakdown in central tolerance driving the immune dysregulation and deficiency seen in GS.<\/jats:p>","DOI":"10.1007\/s10875-026-01992-5","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T04:35:21Z","timestamp":1771302921000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Good\u2019s Syndrome Mirrors a Combined Immunodeficiency with Anti-Cytokine Antibodies in the Total Absence of B Cells"],"prefix":"10.1007","volume":"46","author":[{"given":"Aunonna","family":"Kabir","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Gilbert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dornaz","family":"Almasizadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Alizadehfar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Polito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Langlais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9 P.","family":"Michel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos M.","family":"Tsoukas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"issue":"1","key":"1992_CR1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1136\/jcp.56.1.12","volume":"56","author":"P Kelleher","year":"2003","unstructured":"Kelleher P, Misbah SA. 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