Artigo Acesso aberto Revisado por pares

Autoimmunity/inflammation in a monogenic primary immunodeficiency cohort

2017; Wiley; Volume: 6; Issue: 9 Linguagem: Inglês

10.1038/cti.2017.38

ISSN

2050-0068

Autores

William Rae, Daniel Ward, C. Mattocks, Yifang Gao, Reuben J. Pengelly, Sanjay Patel, Sarah Ennis, Saul N. Faust, Anthony P. Williams,

Tópico(s)

T-cell and B-cell Immunology

Resumo

Primary immunodeficiencies (PIDs) are rare inborn errors of immunity that have a heterogeneous phenotype that can include severe susceptibility to life‐threatening infections from multiple pathogens, unique sensitivity to a single pathogen, autoimmune/inflammatory (AI/I) disease, allergies and/or malignancy. We present a diverse cohort of monogenic PID patients with and without AI/I diseases who underwent clinical, genetic and immunological phenotyping. Novel pathogenic variants were identified in IKBKG , CTLA4 , NFKB1 , GATA2 , CD40LG and TAZ as well as previously reported pathogenic variants in STAT3 , PIK3CD , STAT1 , NFKB2 and STXBP2 . AI/I manifestations were frequently encountered in PIDs, including at presentation. Autoimmunity/inflammation was multisystem in those effected, and regulatory T cell (Treg) percentages were significantly decreased compared with those without AI/I manifestations. Prednisolone was used as the first‐line immunosuppressive agent in all cases, however steroid monotherapy failed long‐term control of autoimmunity/inflammation in the majority of cases and additional immunosuppression was required. Patients with multisystem autoimmunity/inflammation should be investigated for an underlying PID, and in those with PID early assessment of Tregs may help to assess the risk of autoimmunity/inflammation.

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