Rodrigo Hoyos-Bachiloglu1, Janet Chou2. 1. Division of Pediatrics, Department of Pediatric Infectious Diseases and Immunology, Pontificia Universidad Católica de Chile Medical School, Santiago, Chile. 2. Division of Immunology, Department of Pediatrics Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts, USA.
Abstract
PURPOSE OF REVIEW: Advances in genomics and animal models of human disease have enabled the discovery of mechanisms important for host immunity and self-tolerance. Here, we summarize conceptual and clinical discoveries identified from 2018 to 2019 in the field of primary immunodeficiencies and autoimmunity. RECENT FINDINGS: Three new primary immunodeficiencies with autoimmunity were identified and the clinical phenotypes of NFKB1 haploinsufficiency and RASGRP1 deficiency were expanded. A diversity of novel mechanisms leading to autoimmunity associated with primary immunodeficiencies (PIDs) was reported, including pathways important for the metabolism and function of regulatory T cells and germinal B cells, the contribution of neutrophil extracellular traps to plasmacytoid dendritic cell activation and the influence of commensal bacteria on the generation of autoantibodies. With regard to therapeutic developments in the field, we highlight the use of janus kinase inhibitors for immune dysregulation associated with gain-of-function variants in STAT1 and STAT3, as well as the risks of persistent hypogammaglobulinemia associated with rituximab treatment. SUMMARY: Mechanistic studies of PIDs with autoimmunity elucidate key principles governing the balance between immune surveillance and self-tolerance.
PURPOSE OF REVIEW: Advances in genomics and animal models of human disease have enabled the discovery of mechanisms important for host immunity and self-tolerance. Here, we summarize conceptual and clinical discoveries identified from 2018 to 2019 in the field of primary immunodeficiencies and autoimmunity. RECENT FINDINGS: Three new primary immunodeficiencies with autoimmunity were identified and the clinical phenotypes of NFKB1haploinsufficiency and RASGRP1 deficiency were expanded. A diversity of novel mechanisms leading to autoimmunity associated with primary immunodeficiencies (PIDs) was reported, including pathways important for the metabolism and function of regulatory T cells and germinal B cells, the contribution of neutrophil extracellular traps to plasmacytoid dendritic cell activation and the influence of commensal bacteria on the generation of autoantibodies. With regard to therapeutic developments in the field, we highlight the use of janus kinase inhibitors for immune dysregulation associated with gain-of-function variants in STAT1 and STAT3, as well as the risks of persistent hypogammaglobulinemia associated with rituximab treatment. SUMMARY: Mechanistic studies of PIDs with autoimmunity elucidate key principles governing the balance between immune surveillance and self-tolerance.
Authors: Dennis McGonagle; Mary F Kearney; Anthony O'Regan; James S O'Donnell; Luca Quartuccio; Abdulla Watad; Charles Bridgewood Journal: Lancet Rheumatol Date: 2021-12-01