development of the disease. Certain human leukocyte antigen (HLA) class-II gene polymorphisms confer susceptibility to SLE. The HLA class-II genes have also been associated with the presence of certain autoantibodies such as anti-Sm, anti-Ro, anti-La, anti-n RNP (nuclear ribo nuclear protein), and anti-DNA antibodies. Among others, complement C2 and C4 genes confer risk for SLE in certain ethnic groups.
Sex hormones
SLE is predominantly a female disease. First onset of SLE before puberty and after menopause is uncommon. The female predilection becomes less pronounced outside the reproductive age range. These observations suggest a role for endogenous sex hormones in disease predisposition. Abnormal estrogen metabolism has been demonstrated in patients with SLE of both sexes. Women with SLE also have low plasma androgens, including testosterone, dihydrotestosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate. Estrogens may aggravate SLE by prolonging the survival of autoimmune cells, increasing T helper type 2 (Th2) cytokine productions and stimulating B cells to produce autoantibodies. Hyperprolactinaemia has been demonstrated in a proportion of patients with SLE of both sexes. There is preliminary evidence of a defect in the hypothalamo-pituitary-adrenal (HPA) axis in human SLE.
IMMUNOPATHOLOGY
SLE is characterized by a myriad of immune system aberrations that involve B cells, T cells and cells of the monocytic lineage, resulting in polyclonal B cell activation, increased numbers of antibody producing cells (Plasma cells), hypergammaglobulinaemia, autoantibody production and immune complex formation. It appears that excessive and uncontrolled T cells help in the differentiation and activation of autoantibody forming B cells is probably a final common pathway.
Auto antibodies
The central immunological disturbance in patients with SLE is autoantibody production. These antibodies are directed at several self molecules found in the nucleus, cytoplasm and cell surface, in addition to soluble molecules such as IgG and coagulation factors. Antinuclear antibodies are most characteristic and present in more than 95% of patients. Anti-Sm antibodies react with SnRNP (or SmPNP) core proteins, whereas anti-DNA antibodies bind to a conserved nucleic acid determinant widely present on DNA. An |
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association between certain clinical features of SLE and autoantibodies has been established. Such as anti-DNA antibody is associated with glomerulonephritis, psychosis, congenital heart block and sub acute cutaneous lupus.
Cytokines
T helper cells stimulate the production of powerful immune factors called cytokines. To some extent cytokines are indispensable for healing. If overproduced however they can cause inflammation of the body beyond the joints including fever, shock and damage to organs such as liver. Certain cytokines called interferon and interleukins play a critical role in SLE by regulating the secretions of autoantibodies by B cell.
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