Genetic Basis And Laboratory Evaluation Of Systemic Lupus Erthymatosus As An Autoimmune Disease

Systemic lupus erythematosus (SLE) is a prototypic inflammatory autoimmune disorder characterized by multisystem involvement and fluctuating disease activity. Symptoms range from rather mild manifestations such as rash or arthritis to life-threatening end-organ manifestations such as glomerulonephritis or thrombosis. Virtually every organ system is subject to potential damage. Symptoms typically wax and wane over the course of the disease It is prevalent among young women with a peak age of onset between the late teens and early 40s and a female to male ratio of 9:1Understanding the pathogenesis of SLE remains a considerable challenge. Multiple abnormalities of both the innate and adaptive immune system have been described and furthermore, immunological dysfunction precedes clinical presentation by many years. There is a strong genetic basis to SLE, which means that genetic studies can play a key role in furthering our understanding of this disease. Because susceptibility variants are present from birth and are unaffected by the course of the disease, or by its treatment, genetic analysis is, perhaps uniquely, capable of identifying fundamental, causative, disease mechanisms Several candidate genes have been implicated in susceptibility for SLE. The proposed genes include members of the type I interferon (IFN) pathway and genes involved in immunological defense functionsSystemic lupus erythematosus, a disease of immune complex (IC) deposition. Interleukin-10 (IL-10) is thought to promote B-lymphocyte hyperactivity and autoantibody production. Both ICs and Toll-like receptor (TLR) ligands have been shown to stimulate the production of IL-10 by human monocytes Some studies have shown that in SLE the number of circulating T regulatory cells may be decreased during active disease, and that the extent of such decrease may correlate with severity of the diseaseAutoantibody tests have been used extensively in diagnosis and follow-up SLE patients. Immunofluorescent antinuclear antibody (ANA) test using human laryngeal epithelioma cells (HEp-2) cells is still considered the gold standard for screening of autoantibodies .Over 90% of patients with SLE have positive ANA. Significant titres are accepted to be of 1:80 or greater. ANA although sensitive, is far from specific for SLE. A positive ANA is also seen in many other illnesses including systemic sclerosis and polymyositis, as well as some chronic infections. All patients should be screened for extractable nuclear antigens (ENA). Different ENAs are associated with different disease manifestations – for instance, anti-Sm is associated with renal involvement, and anti-Ro with secondary Sjogren’s syndrome Anti-DNA antibodies were shown to play a role in SLE pathogenesis and particularly in kidney damage. Accordingly antibody titres might fluctuate in relation to disease activitySome anti-nucleosome antibody subsets are pathogenic and are involved in the nephritogenic process in SLE. Accordingly, several studies reported: (i) increased plasma circulating nucleosomes positively correlated with an active disease, (ii) nucleosomes in typical glomerular deposits as well as in the basement membrane of non-lesional skin of SLE patients and (iii) a close correlation between nephritis and the presence of anti-nucleosome antibodies. Recent studies reported anti-nucleosome antibodies also in primary anti-phospholipid syndrome and particularly in patients with associated lupus-like disease