Polymorphic haplotypes of the interleukin-10 5? flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis

TLDR

The study aimed to map IL‑10 5′ flanking region haplotype frequencies in juvenile arthritis patients versus controls and assess each haplotype’s functional impact. Haplotype frequencies were determined by sequence‑specific oligonucleotide probing, while transient transfection assays measured reporter transcription and whole‑blood cultures evaluated IL‑10 production per genotype. An ATA haplotype was linked to more extensive joint involvement, lower transcriptional activity compared to GCC, reduced IL‑10 secretion upon LPS stimulation, and a significant association with extended oligoarthritis.

Abstract

Objective To determine the distribution of the interleukin-10 (IL-10) 5′ flanking region haplotypes in children with arthritis and in controls, and to investigate the functional significance of each haplotype. Methods Sequence-specific oligonucleotide probing was used to determine haplotype frequency. Transient transfection studies were used to investigate the transcription of reporter genes driven by each haplotype. Whole blood cultures were performed to assess IL-10 production by each genotype. Results Patients with arthritis involving >4 joints were more likely to have a genotype with an ATA haplotype than those whose arthritis remained restricted to <4 joints. This ATA haplotype was associated with lower transcriptional activity than the GCC haplotype (P > 0.02), and the ATA/ATA genotype was associated with lower IL-10 production under lipopolysaccharide stimulation than other genotypes (P < 0.02). Conclusion The results of this study demonstrate the functional significance of the ATA haplotype and reveal a significant association of genotypes containing this haplotype with extended oligoarthritis.