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- W4290852318 abstract "Tumor necrosis factor receptor–associated factor 3 (TRAF3) is a central regulator of immunity. TRAF3 is often somatically mutated in B cell malignancies, but its role in human immunity is not defined. Here, in five unrelated families, we describe an immune dysregulation syndrome of recurrent bacterial infections, autoimmunity, systemic inflammation, B cell lymphoproliferation, and hypergammaglobulinemia. Affected individuals each had monoallelic mutations in TRAF3 that reduced TRAF3 expression. Immunophenotyping showed that patients’ B cells were dysregulated, exhibiting increased nuclear factor-κB 2 activation, elevated mitochondrial respiration, and heightened inflammatory responses. Patients had mild CD4 + T cell lymphopenia, with a reduced proportion of naïve T cells but increased regulatory T cells and circulating T follicular helper cells. Guided by this clinical phenotype, targeted analyses demonstrated that common genetic variants, which also reduce TRAF3 expression, are associated with an increased risk of B cell malignancies, systemic lupus erythematosus, higher immunoglobulin levels, and bacterial infections in the wider population. Reduced TRAF3 conveys disease risks by driving B cell hyperactivity via intrinsic activation of multiple intracellular proinflammatory pathways and increased mitochondrial respiration, with a likely contribution from dysregulated T cell help. Thus, we define monogenic TRAF3 haploinsufficiency syndrome and demonstrate how common TRAF3 variants affect a range of human diseases." @default.
- W4290852318 created "2022-08-12" @default.
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- W4290852318 date "2022-08-12" @default.
- W4290852318 modified "2023-10-01" @default.
- W4290852318 title "Immunodeficiency, autoimmunity, and increased risk of B cell malignancy in humans with <i>TRAF3</i> mutations" @default.
- W4290852318 cites W1549441204 @default.
- W4290852318 cites W1615175231 @default.
- W4290852318 cites W1808711893 @default.
- W4290852318 cites W1900102168 @default.
- W4290852318 cites W1964876127 @default.
- W4290852318 cites W1978302597 @default.
- W4290852318 cites W1982573460 @default.
- W4290852318 cites W1985778164 @default.
- W4290852318 cites W1989279522 @default.
- W4290852318 cites W1990347373 @default.
- W4290852318 cites W2010160850 @default.
- W4290852318 cites W2015348280 @default.
- W4290852318 cites W2021327465 @default.
- W4290852318 cites W2028330103 @default.
- W4290852318 cites W2029601242 @default.
- W4290852318 cites W2032634316 @default.
- W4290852318 cites W2037211574 @default.
- W4290852318 cites W2046608701 @default.
- W4290852318 cites W2049226548 @default.
- W4290852318 cites W2050437677 @default.
- W4290852318 cites W2057962630 @default.
- W4290852318 cites W2061115519 @default.
- W4290852318 cites W2073836327 @default.
- W4290852318 cites W2087708194 @default.
- W4290852318 cites W2096766502 @default.
- W4290852318 cites W2102771576 @default.
- W4290852318 cites W2104549677 @default.
- W4290852318 cites W2108400693 @default.
- W4290852318 cites W2108446675 @default.
- W4290852318 cites W2110808585 @default.
- W4290852318 cites W2120979959 @default.
- W4290852318 cites W2122734862 @default.
- W4290852318 cites W2127523802 @default.
- W4290852318 cites W2133520037 @default.
- W4290852318 cites W2149791927 @default.
- W4290852318 cites W2163749231 @default.
- W4290852318 cites W2170498830 @default.
- W4290852318 cites W2214074259 @default.
- W4290852318 cites W2259398295 @default.
- W4290852318 cites W2328393125 @default.
- W4290852318 cites W2415473920 @default.
- W4290852318 cites W2534319537 @default.
- W4290852318 cites W2542446037 @default.
- W4290852318 cites W2550031966 @default.
- W4290852318 cites W2622796688 @default.
- W4290852318 cites W2680730285 @default.
- W4290852318 cites W2734534935 @default.
- W4290852318 cites W2768869002 @default.
- W4290852318 cites W2802601652 @default.
- W4290852318 cites W2849483034 @default.
- W4290852318 cites W2888687366 @default.
- W4290852318 cites W2895486342 @default.
- W4290852318 cites W2897399487 @default.
- W4290852318 cites W2951438521 @default.
- W4290852318 cites W2964362771 @default.
- W4290852318 cites W2971078241 @default.
- W4290852318 cites W2976155788 @default.
- W4290852318 cites W2976964184 @default.