Systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease in which organs and cells undergo damage initially mediated by tissue-binding autoantibodies and immune complexes SLE is a multigenic disease. Rare single-gene defects confer high hazard ratios for SLE , including homozygous deficiencies of early components of complement and a mutation on the X chromosome weak gene polymorphisms that increase risk for SLE --HLA DRB1 *0301 and *1501 Innate immunity pathway gene polymorphisms Genes that affect clearance of apoptotic cells or immune complexes Genes that influence neutrophil adherence (ITGAM), and endothelial cell function All these gene polymorphisms/transcription/epigenetic combinations influence immune responses to the external and internal environment; when such responses are too high and/or too prolonged and/or inadequately regulated, autoimmune disease results.

Female sex is permissive for SLE with evidence for hormone effects, genes on the X chromosome, and epigenetic differences between genders playing a role. Women exposed to estrogen-containing oral contraceptives or hormone replacement have an increased risk of developing SLE Exposure to ultraviolet light causes flares of SLE Epstein-Barr virus (EBV) may be one infectious agent that can trigger SLE Current tobacco smoking increases risk for SLE Prolonged occupational exposure to silica (e.g., inhalation of soap powder dust) increases risk Thus, interplay between genetic susceptibility, environment, gender, and abnormal immune responses results in autoimmunity

Pathogenesis and Etiology The proposed pathogenic mechanisms of SLE Interactions between susceptibility genes and environmental factors result in abnormal immune responses, which vary among different patients. activation of innate immunity (dendritic cells, monocyte/macrophages) by CpG DNA, DNA in immune complexes, viral RNA, and RNA in RNA/protein self-antigens; (2) lowered activation thresholds and abnormal activation pathways in adaptive immunity cells (T and B lymphocytes); (3) ineffective regulatory CD4+ and CD8+ T cells; and (4) reduced clearance of immune complexes and of apoptotic cells.

Classification of Lupus Nephritis (International Society of Nephrology and Renal Pathology Society) Class I: Minimal Mesangial Lupus Nephritis Class II: Mesangial Proliferative Lupus Nephritis Class III: Focal Lupus Nephritis Active or inactive focal, segmental or global endo- or extracapillary glomerulonephritis involving <50% of all glomeruli, typically with focal subendothelial immune deposits, with or without mesangial alterations. Class IV: Diffuse Lupus Nephritis Active or inactive diffuse, segmental or global endo- or extracapillary glomerulonephritis involving 50% of all glomeruli, typically with diffuse subendothelial immune deposits, with or without mesangial alterations.     

Class V: Membranous Lupus Nephritis Global or segmental subepithelial immune deposits or their morphologic sequelae by light microscopy and by immunofluorescence or electron microscopy, with or without mesangial alterations. . Class VI: Advanced Sclerotic Lupus Nephritis 90% of glomeruli globally sclerosed without residual activity.

Laboratory TestsLaboratory tests serve to establish or rule out the diagnosis; (2) to follow the course of disease, particularly to suggest that a flare is occurring or organ damage is developing; and (3) to identify adverse effects of therapies. Tests for Autoantibodies -the most important autoantibodies to detect are ANA as the test is positive in >95% of patients High-titer IgG antibodies to double-stranded DNA (dsDNA) (but not to single-stranded DNA) are specific for SLE Antibodies to Sm are also specific for SLE and assist in diagnosis anticardiolipin and the lupus anticoagulant

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