Systemic lupus erythematosus (SLE) is a worldwide chronic autoimmune disease which may affect every organ and tissue. Genetic predisposition, environmental triggers, and the hormonal milieu, interplay in disease development and activity. Clinical manifestations and the pattern of organ involvement are widely heterogenous, reflecting the complex mosaic of disrupted molecular pathways converging into the SLE clinical phenotype. The SLE complex pathogenesis involves multiple cellular components of the innate and immune systems, presence of autoantibodies and immunocomplexes, engagement of the complement system, dysregulation of several cytokines including type I interferons, and disruption of the clearance of nucleic acids after cell death. Use of immunomodulators and immunosuppression has altered the natural course of SLE. In addition, morbidity and mortality in SLE not only derive from direct immune mediated tissue damage but also from SLE and treatment associated complications such as accelerated coronary artery disease and increased infection risk. Here, we review the diagnostic approach as well as the etiopathogenetic rationale and clinical evidence for the management of SLE. This includes 1) lifestyle changes such as avoidance of ultraviolet light; 2) prevention of comorbidities including coronary artery disease, osteoporosis, infections, and drug toxicities; 3) use of immunomodulators (i.e. hydroxychloroquine and vitamin D); and 4) immunosuppressants and targeted therapy. We also review new upcoming agents and regimens currently under study.
Systemic lupus erythematosus (SLE) is an autoimmune disease.
Many of the clinical manifestations of SLE are mediated directly or indirectly by antibody formation and the creation of immune complexes (IC).1
As an example, IC deposition and subsequent complement activation in the kidney is responsible for much of the tissue damage of lupus nephritis). IC have also been detected (by immunofluorescence and/or electron microscopy) at the dermal-epidermal junction in both skin lesions and normal skin, as well as in the choroid plexus, the pericardium, and the pleural cavity.
The pathogenic potential of IC varies, depending on the following:
●The characteristics of the antibody, such as its specificity, affinity, charge, and ability to activate complement or other mediators of inflammation. In the glomerulus, for example, different antibodies may bind to antigens at different sites in the glomerular capillary wall, leading to different histologic and clinical manifestations.
●The nature of the antigen, such as its size and charge. Smaller cationic antigens, for example, are more able to cross the glomerular basement membrane and be deposited in the subepithelial region. The ensuing formation of IC should lead to membranous nephropathy rather than a proliferative glomerulonephritis.
●The ability of the IC to be solubilized by complement and bound to the complement receptor (CR1) on red blood cells (both systems may be defective in SLE).
●The rate at which the IC are cleared by immunoglobulin Fc receptors on monocytes/macrophages in the liver and spleen from the circulation may be genetically impaired in SLE.
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The Sm (Smith) nuclear antigen is a protein complex found within the nucleus of cells. It is a target for autoantibodies, particularly in patients with systemic lupus erythematosus (SLE), an autoimmune disease.
The Sm antigen is part of the small nuclear ribonucleoproteins (snRNPs), which are involved in the splicing of pre-messenger RNA (pre-mRNA) into mature messenger RNA (mRNA). Splicing is a critical step in gene expression, where non-coding regions (introns) are removed from the pre-mRNA, and coding regions (exons) are joined together.
Autoantibodies against the Sm antigen (anti-Sm antibodies) are highly specific for SLE and are considered one of the diagnostic markers for this disease. Although they are specific, they are only present in about 20-30% of patients with SLE. The presence of anti-Sm antibodies can indicate a more severe disease course, but they are not directly correlated with disease activity.
References
1. Bevra H Hahn, MD, Epidemiology and pathogenesis of systemic lupus erythematosus,, UpToDate