Journal Article

Mendelian Causes of Autoimmunity: the Lupus Phenotype

Khoryati, Liliane, Benezech, Sarah, Mathieu, Anne-Laure, Viel, Sebastien, Rieux-Laucat, Fréderic, Belot, Alexandre, Bader-Meunier, Brigitte, Khaldi-Plassart, Samira, Cognard, Jade, Tusseau, Maud

2024

Overview

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by its large heterogeneity in terms of clinical presentation and severity. The pathophysiology of SLE involves an aberrant autoimmune response against various tissues, an excess of apoptotic bodies, and an overproduction of type-I interferon. The genetic contribution to the disease is supported by studies of monozygotic twins, familial clustering, and genome-wide association studies (GWAS) that have identified numerous risk loci. In the early 70s, complement deficiencies led to the description of familial forms of SLE caused by a single gene defect. High-throughput sequencing has recently identified an increasing number of monogenic defects associated with lupus, shaping the concept of monogenic lupus and enhancing our insights into immune tolerance mechanisms. Monogenic lupus (moSLE) should be suspected in patients with either early-onset lupus or syndromic lupus, in male, or in familial cases of lupus. This review discusses the genetic basis of monogenic SLE and proposes its classification based on disrupted pathways. These pathways include defects in the clearance of apoptotic cells or immune complexes, interferonopathies, JAK-STATopathies, TLRopathies, and T and B cell dysregulations.

• Publisher: Springer Nature B.V
• Subject: Age / Antigen-antibody complexes / Apoptosis / Autoimmune diseases / Autoimmunity / Genome-wide association studies / Genomes / Immune clearance / Immunological tolerance / Lupus / Next-generation sequencing / Phenotypes / Systemic lupus erythematosus