IL10 Human Gene Polymorphisms and SLE

The above studies show a correlation of high IL-10 levels with SLE, but do not answer the question of whether high levels of IL-10 are simply a byproduct of SLE and flares, or whether IL-10 plays a role in the disease process. There are some clues, however, that IL-10 may predispose to SLE. Studies showing that healthy relatives of SLE patients have increased numbers of IL-10-producing PBMC 5 or increased levels of IL-

part of the hereditary nature of SLE may stem from differences in tendency to make IL-10. Several studies have attempted to dissect the molecular basis of increased production of IL-10 in SLE patients. Two CA-repeat microsatellites, IL-10.R (-4 kb) and IL-10.G (-1.1 kb), and three single nucleotide polymorphisms (SNP) at -1082 (G/A), -819 (C/T), and -592 (C/A) have been identified and shown to affect IL-10 production.41-44 Attempts to find associations between these IL-10 promoter polymorphisms and SLE have yielded varying results. IL-10.G has been shown to associate with SLE incidence in Scottish, Mexican—American, and Italian populations,45-47 but not in Mexican, Swedish, or Taiwanese populations.48-50 However, in the Taiwanese population, an association was noted between IL-10.G and rapid renal failure in the small subset of patients with this manifestation. Alleles of IL-10.G differ in the populations that have association with SLE incidence, implying that IL-10.G may only be a marker for the presence of another nearby sequence variation that actually causes disease association. No association of the three identified -1082/-819/-592 SNP haplotypes with SLE incidence has been found in five studies of Chinese, Dutch and British populations.41,51-54 However, the GCC haplotype was associated with anti-Ro auto-antibodies in British Caucasians, while the ATA haplotype was associated with renal disease in Chinese52 but not Dutch53 or British54 populations, and with neuropsychiatric SLE in Dutch Caucasians 53 but not Chinese patients.52 These differences in findings may be due simply to genetic differences in the populations studied. However, a recent finding by Gibson et al of seven more SNP in the -1.3 to -4 kb region of the IL-10 promoter means that further evaluation of previously studied populations may be warranted.55 These new SNP, along with the previously identified polymorphisms, were examined in an African—American cohort. Haplotypes associated with high IL-10 production were associated with SLE in this population.55 These studies suggest that high levels of IL-10 may be one of several predisposing factors for SLE incidence and severity.

Figure 2. Interleukin-10 effects on B cells.

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