IL-1 and TNF gene polymorphisms in patients with juvenile idiopathic arthritis treated with tnf inhibitors

Rolando Cimaz ^1*, Marie-Angélique Cazalis ¹, Charlotte Raynaud ¹, Valeria Gerloni ², Francesco Zulian ³, Martina Biggioggero ², Giorgia Martini ³, Irene Pontikaki ², Flavio Fantini ², Bruno Mougin ¹ and Pierre Miossec ¹

¹ Unité Mixte Hospices Civils de Lyon-BioMérieux, Lyon, France
² Pediatric Rheumatology, Ospedale Gaetano Pini and University of Milano, Milano, Italy
³ Department of Pediatrics, University of Padova, Italy

^* To whom correspondence should be addressed. E-mail: roland.cimaz{at}chu-lyon.fr.

Accepted 18 February 2007

Abstract

Objective:To investigate the genetic contribution of cytokine gene polymorphisms (Interleukin-1, IL-1, and Tumour necrosis factor a, TNF-a) on disease phenotype and on response to TNF-blocking agents in a population of patients with Juvenile Idiopathic Arthritis (JIA).

Methods:A cohort of 107 consecutive patients with JIA who were receiving treatment with anti-TNF agents were enrolled in this study. Genetic polymorphisms for IL1B +3954, IL1RA +2018, TNF-a -238 and TNF-a -308 were performed by Enzyme Linked Oligo Sorbent Assay, and compared with those obtained from 630 healthy Caucasians and from 263 adult patients with rheumatoid arthritis. Relevant demographic, clinical, and laboratory data were collected from clinical charts and entered into a customized database. Chi-square analysis was performed to compare cytokine polymorphisms with disease type according to the ILAR criteria, presence of uveitis, rheumatoid factor and anti-nuclear antibody positivity, erosive disease, frequency of adverse effects to anti- TNF, and clinical response after 3 months.

Results:The T/T genotype of the IL-1B +3954 polymorphism was absent in patients with JIA and present in 5% of controls (p = 0.015). No statistically significant correlation was found between the studied polymorphisms and clinical or laboratory variables considered. Clinical response to TNF inhibitors at 3 months was not associated with the genetic polymorphisms considered.

Conclusion:In our cohort, the absence of the rare IL-1B +3954 gene polymorphism was associated with JIA, but without specificity to particular disease phenotypes. The TNF and IL-1 gene polymorphism studied did not appear to be associated with response to anti- TNF treatment.

Keywords: cytokines, juvenile idiopathic arthritis, polymorphisms, tumor necrosis factor

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