Monogenic lupus: Dissecting heterogeneity

Publication date: Available online 8 August 2019Source: Autoimmunity ReviewsAuthor(s): Ommar Omarjee, Cécile Picard, Cécile Frachette, Marion Moreews, Frederic Rieux Laucat, Pauline Sprauel, Sebastien Viel, Jean-Christophe Lega, Brigitte Bader-Meunier, Thierry Walzer, Anne-Laure Mathieu, Rolando Cimaz, Alexandre BelotAbstractSystemic lupus erythematosus (SLE) is a severe lifelong multisystem autoimmune disease characterized by the presence of autoantibodies targeting nuclear autoantigens, increased production of type I interferon and B cell abnormalities. Clinical presentation of SLE is extremely heterogeneous and different groups of disease are likely to exist. Recently, childhood-onset SLE (cSLE) cases have been linked to single gene mutations, defining the concept of monogenic or Mendelian lupus. Genes associated with Mendelian lupus can be grouped in at least three functional categories. First, complement deficiencies represent the main cause of monogenic lupus and its components are involved in the clearance of dying cells, a mechanism also called efferocytosis. Mutations in extracellular DNASE have been also identified in cSLE patients and represent additional causes leading to defective clearance of nucleic acids and apoptotic bodies. Second, the study of Aicardi-Goutières syndromes has introduced the concept of type-I interferonopathies. Bona fide lupus syndromes have been associated to this genetic condition, driven by defective nucleic acids metabolism or innate ...
Source: Autoimmunity Reviews - Category: Allergy & Immunology Source Type: research