Differential CCR5Δ32 allelic frequencies in juvenile idiopathic arthritis subtypes: evidence for different regulatory roles of CCR5 in rheumatological diseases

Abstract

Background: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood and is characterized by persistent arthritis for at least 6 weeks. Its aetiopathogenesis is unknown but there is strong evidence that there is a substantial genetic component. Chemokine receptors genes are among the candidate genes for association with arthritis and other inflammatory diseases. The CC chemokine receptor 5 (CCR5)Δ32 polymorphism has been associated with rheumatoid arthritis (RA), conferring a protective effect.

Objective: To determine whether the CCR5Δ32 polymorphism is associated with JIA and RA in Brazilian patients.

Methods: We investigated 203 RA patients, 101 JIA patients, and 104 healthy individuals by amplification of the CCR5Δ32 deletion. We compared the allelic frequencies among these groups, as well as among different JIA subtypes.

Results: The frequency of the Δ32 allele was higher in JIA patients (9.4%) as compared to control subjects (3.8%) and RA patients (3.2%). Grouping the patients according to JIA subtypes, we observed a higher CCR5Δ32 allelic frequency in the subtypes with a greater inflammatory component: 4.1% in oligoarticular (n = 49), 11.2% in polyarticular (n = 40) [9.5% in rheumatoid factor negative (RF−) and 33.3% in RF positive (+)], and 25% in systemic JIA (n = 12).

Conclusions: This study suggests that in JIA, unlike in RA, CCR5Δ32 does not have a protective effect, but instead it could be a factor associated with more inflammatory forms of the disease. These observations give rise to new questions about the mechanism and the cellular types involved in JIA as well as about the aetiology of JIA.