Systemic Lupus Erythematosus: Old and New Susceptibility Genes versus Clinical Manifestations

Abstract

Systemic Lupus Erythematosus (SLE) is one of the most relevant world-wide autoimmune disorders. The formation of autoantibodies and the deposition of antibody-containing immune complexes in blood vessels throughout the body is the main pathogenic mechanism of SLE leading to heterogeneous clinical manifestations and target tissue damage. The complexity of etiology and pathogenesis in SLE, enclosing genetic and environmental factors, apparently is one of the greatest challenges for both researchers and clinicians. Strong indications for a genetic background in SLE come from studies in families as well as in monozygotic and dizygotic twins, discovering several SLE-associated loci and genes (e.g. IRF5, PTPN22, CTLA4, STAT4 and BANK1). As SLE has a complex genetic background, none of these genes is likely to be entirely responsible for triggering autoimmune response in SLE even if they disclosure a potentially novel molecular mechanisms in the pathogenesis' disease. The clinical manifestations and disease severity varies greatly among patients, thus several studies try to associate clinical heterogeneity and prognosis with specific genetic polymorphisms in SLE associated genes. The continue effort to describe new predisposing or modulating genes in SLE is justified by the limited knowledge about the pathogenesis, assorted clinical manifestation and the possible prevention strategies. In this review we describe newly discovered, as well as the most studied genes associated to SLE susceptibility, and relate them to clinical manifestations of the disease.

Glycoprotein 96 polymorphisms are associated with the risk of systemic lupus erythematosus: A case‐control study

“…Previous familial and twin studies on SLE reported several risk loci and genes including IRF5 , PTPN22 , CTLA4 , STAT4 , and BANK1 . In addition, our genetic study first presented GP96 as an SLE‐associated gene.…”

Diet, Gut Microbiota and Non-Alcoholic Fatty Liver Disease: Three Parts of the Same Axis

“…These findings were corroborated in mice fed with HFD, observing that those animals that were treated with F. prausnitzii as a probiotic presented a lower hepatic lipid and lower plasma levels of liver transaminases (AST and ALT), suggesting a healthier liver than the one of the HFD counterpart mice (Table 1) [74]. Moreover, the presence of F. prausnitzii increases the expression levels of an inhibitor cell cycle progression, CDKN1A, which encodes for the p21 protein, whose levels are inversely associated with NAFLD progression and fibrosis [87]. Faecalbacterium prausnitzii is a butyrate-producing bacterium, from the Firmicutes phylum ( Figure 1) [84].…”

Vitamin D receptor gene BsmI polymorphisms in Egyptian children and adolescents with systemic lupus erythematosus

“…Systemic lupus erythematosus (SLE) is one of the most relevant worldwide autoimmune disorders with a broad spectrum of autoimmune phenomena, clinical symptoms, and unknown etiology [1] SLE diverse presentations range from arthritis and malar rash through anemia and thrombocytopenia to nephritis, serositis, seizures, and psychosis [2] Complex interactions between environmental, genetic, and hormonal factors have been linked with the phenotype and progression of SLE [3] One such environmental factor is vitamin D, a steroid hormone recognized as essential for bone and mineral homeostasis. Sun exposure is the major source of vitamin D, but it is also available in some foods and supplements.…”