The aim of the Monogenic Systemic and Incomplete Lupus Erythematosus GCEP will be to curate the validity of gene-disease associations in the context of clinical phenotypes consistent with lupus. Lupus is a chronic multisystem and phenotypically heterogeneous autoimmune disease. Loss of immune tolerance leads to the generation of autoreactive immune cells leading to inflammation and damage of multiple organs, including the skin, kidney, and CNS.

The diagnosis of Systemic Lupus Erythematosus (SLE) is made based on clinical and laboratory findings, typically according to the three commonly used classification criteria (the ACR 1997, SLICC 2012, and ACR/EULAR 2019 classification criteria for SLE). Despite improvements over time, these criteria fail to identify all cases, and many patients, particularly at time of initial presentation, do not meet classification criteria and are described by terminology including “incomplete lupus” and “lupus-like” disease. Evidence strongly suggests a genetic component in lupus susceptibility, with over 50 genes having been postulated as potential causes of monogenic lupus or lupus-like disease, and additional gene variants described in association with lupus. However, the level of certainty and strength of gene-disease associations have not been well characterized. 

Our gene list includes 55 genes, selected by expert opinion based on literature review and refined in discussion with members of the Lupus GCEP, the Monogenic Autoinflammatory GCEP leadership, and the broader RAD CDWG.