Systemic Lupus Erythematosus (SLE) is a systemic inflammatory autoimmune disease characterised by the production of autoantibodies (such as the anti nuclear antibodies anti-Sm, anti-Ro/SSA and anti-La/SSB) with patients presenting with a diverse array of different clinical manifestations including skin, joint, haematologic, neurologic, renal and other organ involvement. SLE is predominately a female disease, affecting females and males in a ration of 9:1. Onset is usually between puberty and menopause with onset outside this range less common. Patients often undergo repeated cycles of flare ups and remissions. Complications of the disease seen in nearly half of all patients include glomerulonephritis and impaired renal function and/or neurological symptoms such as seizures, psychiatric symptoms, peripheral neuropathies or stroke.
The exact aetiology of SLE is unknown, though it is thought to have a genetic component as well as environmental and hormonal components. The genetic component of SLE is supported by twin and family studies. The concordance of SLE in monozygotic twins in approximately 25 – 50% compared to only 5% in dizygotic twins. Population studies have revealed that susceptibility to SLE is associated with HLA class II, in particular with haplotypes bearing the DRB1*03:01, DQB1*02:01 and the DRB1*15:01, DQB1*06:02 alleles. These alleles were present in over 65% of SLE cases. The DRB1*03:01 allele carries a higher risk than the DRB1*15:01. Individuals homozygous for DRB1*03:01 or compound heterozygous for DRB1*03:01 and DRB1*15:01 carry the highest risk. The DRB1*03:01 allele is associated with production of anti-Ro/SSA and anti-La/SSB autoantibodies while the DRB1*15:01 allele is associated with production of anti-Sm autoantibodies.
Genome wide association studies have also identified a number of non HLA genes that are risk factors for SLE. These include genes for the Fc receptors for immunoglobulin G which mediate clearance of immune complexes. The Arg620 to Trp polymorphism in the Protein tyrosine Phosphatase, non-receptor type-22 (PTPN22) gene (which codes for a powerful inhibitor of T-cell activation) may also have a role in SLE.
Genetic testing for SLE has significant clinical relevance for efforts to more fully characterise the aetiology and pathway of development of SLE and may lead to improved diagnostic and prognostic tools. Developments in genetic testing for SLE may also lead to the development of more specific therapies for SLE and related conditions.
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