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  • Title: Differential effect of IL10 and TNF{alpha} genotypes on determining susceptibility to discoid and systemic lupus erythematosus.
    Author: Suárez A, López P, Mozo L, Gutiérrez C.
    Journal: Ann Rheum Dis; 2005 Nov; 64(11):1605-10. PubMed ID: 15800006.
    Abstract:
    OBJECTIVE: To ascertain the possible involvement of functional interleukin 10 (IL10) and tumour necrosis alpha (TNFalpha) cytokine promoter polymorphisms on the susceptibility to discoid and systemic lupus erythematosus (DLE, SLE), and their associations with immunological features. METHODS: Single nucleotide polymorphisms of the IL10 (-1082, -819, and -592) and TNFalpha (-308) genes were determined using allele specific probes in 248 lupus patients and 343 matched controls. To assess functional significance of genotypes, basal mRNA cytokine levels were quantified in 106 genotyped healthy controls by real time RT-PCR. Specific autoantibodies and cutaneous manifestations were analysed in SLE patients and associated with functional genotypes. RESULTS: After analysing the distribution of IL10 and TNFalpha transcript levels according to promoter genotypes in healthy individuals, patients and controls were classified into functional single and combined genotypes according to the expected high or low constitutive cytokine production. High TNFalpha genotypes (-308AA or AG) were associated with SLE independently of IL10 alleles, whereas the risk of developing DLE and the prevalence of discoid lesion in SLE were higher in the high IL10/low TNFalpha producer group (-1082GG/-308GG). Cytokine interaction also influences the appearance of autoantibodies. Antibodies against Sm are prevalent among low producer patients for both cytokines, a genotype not associated with lupus incidence, whereas low IL10/high TNFalpha patients have the highest frequency of antibodies to SSa and SSb. CONCLUSIONS: IL10/TNFalpha interaction influences susceptibility to DLE and the appearance of specific autoantibodies in SLE patients, whereas high TNFalpha producer genotypes represent a significant risk factor for SLE.
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