No association of IL-12p40 pro1.1 polymorphism with juvenile idiopathic arthritis

Abstract

BackgroundIL-12p40 plays an important role in the activation of the T-cell lines like Th17 and Th1-cells. Theses cells are crucial in the pathogenesis of juvenile idiopathic arthritis. A polymorphism in its promoter region and the genotype IL12p40 pro1.1 leads to a higher production of IL-12p40. We studied whether there is a difference in the distribution of the genotype in patients with JIA and the healthy population.MethodsIn 883 patients and 321 healthy controls the IL-12p40 promoter genotype was identified by ARMS-PCR.ResultsThere is no association of IL-12p40 pro polymorphism neither in patients with JIA compared to controls nor in subtypes of JIA compared to oligoarthritis. We found a non-significant tendency of a higher prevalence of the genotype pro1.1 in systemic arthritis (32.4 %) and in rheumatoid factor negative polyarthritis (30.5 %) and a lower pro1.1 genotype in persistent oligoarthritis (20.7 %) and in enthesitis-related arthritis (17 %). Likelihood of the occurrence of genotype IL12-p40 pro1.1 in patients with systemic arthritis (OR 1.722, CI 95 % 1.344-2.615, p 0.0129) and RF-negative polyarthritis (OR 1.576, CI 95 % 1.046-2.376, p 0.0367) compared to persistent oligoarthritis was significantly higher. This was also true for comparison of their homozygous genotypes IL-12p40 pro 1.1 and 2.2 in systemic arthritis (OR 1.779, CI 95 % 1.045-3.029, p 0.0338). However, in Bonferroni correction for multiple hypothesis this was not significant.ConclusionA tendency of a higher prevalence of the genotype IL-12p40 pro1.1 in systemic arthritis and in rheumatoid factor negative polyarthritis was observed but not significant. Further investigations should be done to clarify the role IL-12p40 in the different subtypes of JIA.

Transcription factor motif enrichment in whole transcriptome analysis identifies STAT4 and BCL6 as the most prominent binding motif in systemic juvenile idiopathic arthritis

“…STAT4 is mainly expressed in myeloid cells and is the transcription factor downstream of IL-12, which has been identified as a potential biomarker in sJIA, but has not been discussed as a potential therapeutic target so far [ 16 – 18 ]. We have previously shown that the likelihood of the occurrence of a polymorphism enhancing IL-12 expression was somewhat higher in patients with sJIA compared to other forms of JIA, which points toward IL-12 being more prominent in sJIA than previously thought [ 19 ]. In our array analysis, IL-12 was not differentially expressed; however, the IL-23 receptor, which is involved in IL-12 downstream signaling was downregulated in active disease (fold change 2.5, p = 0.012, Fig.…”