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. 2005 Mar 30;64(11):1605–1610. doi: 10.1136/ard.2004.035048

Differential effect of IL10 and TNFα genotypes on determining susceptibility to discoid and systemic lupus erythematosus

A Suarez 1, P Lopez 1, L Mozo 1, C Gutierrez 1
PMCID: PMC1755257  PMID: 15800006

Abstract

Objective: To ascertain the possible involvement of functional interleukin 10 (IL10) and tumour necrosis α (TNFα) 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 TNFα (–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 TNFα 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 TNFα 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 TNFα 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 TNFα patients have the highest frequency of antibodies to SSa and SSb.

Conclusions: IL10/TNFα interaction influences susceptibility to DLE and the appearance of specific autoantibodies in SLE patients, whereas high TNFα producer genotypes represent a significant risk factor for SLE.

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Figure 1.

Figure 1

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 Relation between IL10 and TNFα genotypes and constitutive cytokine expression. Interleukin 10 (IL10) (panel A) and tumour necrosis factor α (TNFα) (panel B) basal mRNA levels were quantified in peripheral blood cells of 106 genotyped healthy subjects by a highly sensitive real time RT-PCR technique, as described in Methods. The distribution of transcript levels according to promoter genotypes was analysed. Horizontal bars are median values. Significance was evaluated by the Mann–Whitney U test: IL10 GCC/GCC v other genotypes, p = 0.026; TNFα GG v other genotypes, p = 0.021.

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