biostudies-literatureAbolhassani HNational Center for Advancing Translational SciencesSquare FoundationBundesministerium für Bildung und ForschungFrench Foundation for Medical ResearchIntramural NIH HHSNCATS NIH HHSGrandir—Fonds de solidarité pour l’enfanceHoward Hughes Medical InstituteNIAID NIH HHSFrench National Research AgencyInstitut National de la Santé et de la Recherche MédicaleNational Institutes of HealthSt. Giles FoundationEuropean CommissionNational Institute of Allergy and Infectious DiseasesWilhelm Sander-StiftungDeutsche ForschungsgemeinschaftCrafoord FoundationNational Cancer InstituteParis Cité UniversityRockefeller Universitye20250016https://www.ebi.ac.uk/biostudies/studies/S-EPMC12435966biostudies-literatureUnknown1(4)Predominantly antibody deficiency (PAD) is the most prevalent form of human inborn errors of immunity (IEI). PAD is characterized by recurrent bacterial infections, immune dysregulation, and impaired immunoglobulin production. A monogenic cause of PAD can be identified in about 20% of cases. Approximately 10% of patients carry heterozygous mutations in the tumor necrosis factor receptor superfamily member 13B gene (<i>TNFRSF13B</i>), encoding the B cell surface protein TACI. Heterozygous variants in <i>TNFRSF13B</i> are not sufficient to cause PAD, as approximately 1% of the healthy population carries one of these variants. To identify additional genetic contributors to the immune defect in these individuals, we examined the exomes of 161 PAD patients with rare-damaging variants in <i>TNFRJournal of human immunityRe-evaluation of the contribution of &lt;i&gt;TNFRSF13B&lt;/i&gt; variants to antibody deficiency.PMC12435966390874280GAIN 01GM2206AAI-061093UL1TR0018662023.115.1UL1 TR001866#519635399Z99 CA999999SFB1160/3_B5AI-08603ANR-10-LABX-62-IBEIDP01AI061093P01 AI061093EQU201903007798390939984ANR-10-IAHU-01Cunningham-Rundles CProietti MGrimbacher BBoisson BYang MRezaei NCasanova JLHammarstrom LDelavari SAbolhassani HSchaffer AAMaffucci PCaballero-Oteyza APan-Hammarstrom QfalseRe-evaluation of the contribution of &lt;i&gt;TNFRSF13B&lt;/i&gt; variants to antibody deficiency.Predominantly antibody deficiency (PAD) is the most prevalent form of human inborn errors of immunity (IEI). PAD is characterized by recurrent bacterial infections, immune dysregulation, and impaired immunoglobulin production. A monogenic cause of PAD can be identified in about 20% of cases. Approximately 10% of patients carry heterozygous mutations in the tumor necrosis factor receptor superfamily member 13B gene (<i>TNFRSF13B</i>), encoding the B cell surface protein TACI. Heterozygous variants in <i>TNFRSF13B</i> are not sufficient to cause PAD, as approximately 1% of the healthy population carries one of these variants. To identify additional genetic contributors to the immune defect in these individuals, we examined the exomes of 161 PAD patients with rare-damaging variants in <i>TNFR2025-01-01T00:00:00Z2025 Nov2026-06-06T21:57:50.822Z2026-06-05T03:11:57.58ZS-EPMC124359664095916410.70962/jhi.20250016