IL‐10 Promoter −1082 Polymorphism is Associated with Elevated IL‐10 Levels in Control Subjects but Does not Explain Elevated Plasma IL‐10 Observed in Sjögren's Syndrome in a Hungarian Cohort

Abstract

The aim of this study was to investigate the frequency of the À1082 polymorphism of the interleukin-10 (IL-10) gene and the soluble IL-10 levels in Hungarian primary Sjögren's syndrome (SS) patients. Ninety-nine SS patients and 135 healthy volunteers were examined. Samples were analysed by the PCR restriction fragment length polymorphism method, and IL-10 plasma levels were assesed by a commercial enzyme-linked immunosorbent assay. IL-10 plasma levels were higher in the primary SS patients (36.4 AE 57.5 pg/ml, n ¼ 99) compared with the healthy subjects (9.9 AE 20.3 pg/ml, n ¼ 135, P ¼ 10 À6 ). The elevated IL-10 phenotype of SS patients was not associated with increased G allele frequency as reported earlier, while in the control group, we found higher IL-10 levels among the subjects who were carriers of the GG genotype (17.7 AE 23.2 pg/ml) as compared with the other two genotype carriers (AA 8.98 AE 16.5 and GA 8.5 AE 21.1 pg/ml, P ¼ 0.01). Our data do not support previous observations indicating an association between deregulated IL-10 secretion in SS and higher G allele frequency. However, the results clearly demonstrate that GG homozygosity is associated with elevated IL-10 levels in apparently healthy subjects, but this cannot account for the IL-10-related specific disease features observed in SS. Thus, other genetic factors contribute to the clinical spectrum of this heterogeneous disease at least in the Hungarian population.

Analysis of IL10 haplotypes in primary Sjögren’s syndrome patients from Western Mexico: Relationship with mRNA expression, IL-10 soluble levels, and autoantibodies

“…Furthermore, Fox et al suggested that salivary gland CD4+ T cells produce over 40-fold more IL10 mRNA than peripheral blood CD4+ T cells from the same patient or normal controls, moreover, increased levels of IL-10 were found in saliva of pSS patients suggesting that the elevated mRNA levels detected in their glandular tissue correlated with local protein synthesis [49]. Primary Sjögren's syndrome patients also showed increased levels of sIL-10 in concordance with previous reports [2,3,20,24,53] suggesting an important role of this cytokine in the pathogenesis of the disease. The immunostimulatory properties of IL-10 in primary Sjögren's syndrome have been evaluated in mice transgenic for IL-10 in which the mouse IL10 gene was regulated by the human salivary amylase promoter.…”

“…In primary Sjögren's syndrome, the IL10 polymorphisms and their haplotypes have been analyzed showing discordant results, -1082 GG and GCC haplotype have been associated as genetic risk factors for pSS in Caucasians [8,20,21], while ATA haplotype has been considered as risk factor in Asians [8,22]. However, some reports in Caucasians have not associated IL10 polymorphisms and haplotypes with susceptibility to pSS [23][24][25].…”

The Association between TNF-α, IL-10 Gene Polymorphisms and Primary Sjögren’s Syndrome: A Meta-Analysis and Systemic Review

“…In previous study, pSS patients who carried the “GCC” haplotype were identified to have a significantly elevated level of plasma IL-10 compared with GCC-negative patients [18]. The patients with GCC haplotype were also confirmed to have an earlier onset of pSS, whereas other investigators could not find the kind of difference [19], [21]. In other study, GCC haplotype was shown to be associated with clinical manifestation of some autoimmune disease.…”

“…A total of 9 relevant studies with IL-10, TNF-αgene polymorphisms and susceptibility to pSS were left for final inclusion in the meta-analyses. 7 articles were identified to assess the SNPs within IL-10 gene and pSS [17], [18], [19], [20], [21], [22], one of which also contained the data about TNF-α polymorphisms [23]. Then, the remaining 2 studies focused solely on TNF-α gene polymorphisms [24], [25].…”

Monocyte-Derived Interleukin-10 Depresses the Bordetella pertussis - Specific Gamma Interferon Response in Vaccinated Infants

“…Since the PBMC of only some of the infants in this study spontaneously secreted detectable levels of IL-10 and, consequently, low IFN-␥ concentrations upon stimulation with FHA and PT, we investigated whether these differences could be linked to genetic polymorphisms of the IL-10 gene promoter which have been reported to influence the constitutive IL-10 production (14,24,25).…”