Abstract
Systemic lupus erythematosus (SLE) is a clinically and genetically heterogeneous autoimmune disease. The etiology of lupus and the contribution of genetic, environmental, infectious and hormonal factors to this phenotype have yet to be elucidated. The most straightforward approach to unravel the molecular pathogenesis of lupus may rely on studies of patients who present with early-onset severe phenotypes. Typically, they have at least one of the following clinical features: childhood onset of severe disease (<5 years), parental consanguinity, and presence of family history for autoimmune diseases in a first-degree relative. These patients account for a small proportion of patients with lupus but they inform considerable knowledge about cellular pathways contributing to this inflammatory phenotype. In recent years with the aid of new sequencing technologies, novel or rare pathogenic variants have been reported in over 30 genes predisposing to SLE and SLE-like diseases. Future studies will likely discover many more genes with private variants associated to lupus-like phenotypes. In addition, genome-wide association studies (GWAS) have identified a number of common alleles (SNPs), which increase the risk of developing lupus in adult age. Discovery of a possible shared immune pathway in SLE patients, either with rare or common variants, can provide important clues to better understand this complex disorder, it’s prognosis and can help guide new therapeutic approaches. The aim of this review is to summarize the current knowledge of the clinical presentation, genetic diagnosis and mechanisms of disease in patents with lupus and lupus-related phenotypes.
Highlights
Systemic lupus erythematosus (SLE; OMIM 152700) is a complex autoimmune disease from a clinical standpoint and from genetic and immunological aspects of the disease
It was previously thought that the relevant genetic variants and the causal molecular pathway involved in lupus were associated with distinct clinical presentations
A genome-wide association study showed that the variant rs1456896 in the 5 UTR of IKZF1 was relevant to lupus nephritis [105]
Summary
Systemic lupus erythematosus (SLE; OMIM 152700) is a complex autoimmune disease from a clinical standpoint and from genetic and immunological aspects of the disease. The term monogenic lupus has been introduced to denote SLE patients who carry high-penetrance either dominantly or recessively inherited pathogenic variants in a single gene. Among these rare forms of the disease, mutations in the genes encoding for complement pathway are the first and foremost described. Apart from the complement deficiencies, the vast majority of the single gene defects that lead to monogenic lupus are categorized under the umbrella of type I interferonopathies [8,9] This term is broadly defined but essentially indicates persistent upregulation of type I interferon (IFN) signaling as measured by high expression of interferon-stimulated genes (ISGs).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
