Cytokine Gen Polymorphisms Involved in Susceptibility and Severity of Oligoarticular Juvenile Idiopathic Arthritis (JIA)-Associated Uveitis

Abstract

Purpose: : The aim of this study was to identify key cytokine polymorphisms associated with disease susceptibility, clinical phenotype, and outcome in patients with oligoarticular juvenile idiopathic arthritis (JIA)-associated uveitis as compared to those with JIA without uveitis.

Methods: : Eighty-six patients with oligoarticular JIA were classified according to International League of Associations for Rheumatology (ILAR) criteria and divided into groups depending on antinuclear antibodies (ANA) positive/negative and patients with/without JIA-associated uveitis. Informed consent, clinical and laboratory data were collected into a database. TaqMan PCR amplification was used to genotype 5 single nucleotide polymorphisms in cytokine genes; TNF- -308, IL-1β-511, IL-6-174, IL-10–1082 and IL-1Ra rs4251961. Multivariate analysis was performed to assess statistical relation between cytokine polymorphisms, uveitis appearance, ANA positivity/negativity, erythrocyte rate sedimentation (ESR) at arthritis onset and age onset of arthritis (AOA).

Results: : Twenty seven patients presented JIA-associated uveitis and fifty-nine showed oligoarticular JIA without uveitis. In our sample, ANA have shown a very low positive predictive value (32.8%) and also a low negative predictive value (75%). Studied polymorphysms showed no significant relation with JIA-associated uveitis: TNF- -308 (p=0.6), IL-1β -511 (p=0.8), IL-6 -174 (p=0.6), IL-10 –1082 (p=0.7) and IL-1Ra rs4251961 (p=0.7), neither showed a good positive or negative predictive value. Unlike, AOA has shown a statistical significance (p=0.02) related to uveitis appearance with a cut point of 3 years old. Furthermore, ESR has also shown a clear relation with uveitis appearance (p=0.00) with a cut point in 22 mm/h.

Conclusions: : We conclude that ANA are not an accurate test for predicting uveitis appearance in oligoarticular JIA patients, neither our 5 studied polymorphysms. Furthermore, we recommend, after an external validation, a uveitis screening regimen which combines the ESR and AOA as a new guideline in the oligoarticular JIA-associated uveitis screening. In case of patients with a very high risk of developing uveitis would have an ESR ≥ 22 mm/h and an AOA < 3 years and it would be advisable to be examined every month. Unlike, patients with a low risk of developing uveitis, with an ESR < 22 mm/h and AOA ≥ 3 years, could be examined every 12 months.

Keywords: genetics • uveitis-clinical/animal model • autoimmune disease