Systemic Lupus erythematosus (SLE)
SLE is an autoimmune disease characterised by the production of antibodies to components of the cell nucleus in association with a diverse array of clinical manifestations that can affect virtually any organ of the body. Prevalence is thought to be somewhere in the range of 20-70 cases per 100,000.
The disease is chronic but does have relatively symptom free periods. Inflammation and organ damage can occur from either deposition of immune complexes or from binding of autoantibodies to cell surfaces leading to complement activation and tissue damage. The underlying cause of SLE is unknown but it involves both genetic and environmental factors.
Genetic factors include a strong linkage with MHC class II loci. In addition, polymorphisms in genes involved in important arms of the immune system including the innate (IRF5, STAT4, IRAK1, TNFAIP3, SPP1, TLR7), lymphocyte signalling (PTPN22, OX40L, PD-1, BANK-1, LYN, BLK) and clearance of immune complexes (complement components C1q, C4 and C2, Fc gamma RIIA, RIIIB, CRP, and integrin alpha M) have also been found.
Dysregulation of apoptosis is also thought to be involved. Environmental factors implicated in SLE include infections, ultraviolet light, medications including anti-tumour necrosis factor agents. Hormonal factors also are important. The use of oestrogen containing oral contraceptives increases the risk of SLE and there is a much higher prevalence in women particularly during the reproductive years.
The diverse clinical manifestations of SLE are accompanied by autoantibodies directed against at least 100 different antigens. SLE can react with nuclear, cytoplasmic and surface cell antigens along with complement components. The disease manifestations are so diverse that two patients may satisfy the criteria for SLE diagnosis but do not exhibit the same clinical findings. Some of the classification criteria for SLE are a malar rash, discoid rash, oral ulcers, arthritis, renal disorders and serositis.
Antinuclear antibodies (ANAs) are found to be present in almost all patients with SLE and is the most sensitive test for SLE. However, ANAs are not specific to SLE and can be found in many other autoimmune disorders along with healthy individuals. Important markers in SLE are histones, nucleosomes, dsDNA, Sm, RNP, PCNA, C1q and Ku to name a few. Nucleosomes, dsDNA and Sm antigens exhibit the highest disease specificity.
Sherer et al, Semin Arthritis Rheum. 2004, 34:501-537
Hoffman et al, Ann Rheum Dis. 2004 63:1155-1158
Sawalha AH and Harley JB, Curr Opin Rheumatol. 2004, 16:534-540
D’Cruz Dp, Khamashta MA and Hughes GR, Lancet 2007, 369:587-96
Rahman A and Isenberg DA, N Engl J Med. 2008 358:929-39
Tan et al, Arthritis Rheum. 1999, 42:455-464
Kavanaugh AF and Solomon DH, Arthritis Rheum. 2002 47:546-555
Guillermo et al, Semin Arthritis Rheum. 2010, 39(4): 257