Anti-IL21 Monoclonal antibody, clone GGB32

Objective: To test the hypothesis that non-HLA single-nucleotide polymorphisms (SNPs) associated with the risk of juvenile idiopathic arthritis (JIA) are risk factors for an unfavourable disease outcome at long-term follow-up.Methods: The Nordic JIA cohort is a prospective multicentre study cohort of patients from the Nordic countries. In all, 193 patients met the inclusion criteria of having an 8year follow-up assessment and available DNA sample. Seventeen SNPs met the inclusion criteria of having significant associations with JIA in at least two previous independent study cohorts. Clinical endpoints were disease remission, actively inflamed joints and joints with limitation of motion (LOM), articular or extra-articular damage, and history of uveitis.Results: Evidence of associations between genotypes and endpoints were found for STAT4, ADAD1-IL2-IL21, PTPN2, and VTCN1 (p=0.003-0.05). STAT4_rs7574865 TT was associated with the presence of actively inflamed joints [odds ratio (OR) 20.6, 95% confidence interval (CI) 2.2->100, p=0.003] and extra-articular damage (OR 7.9, 95% CI 1-56.6, p=0.057). ADAD1_rs17388568 AA was associated with a lower risk of having joints with LOM (OR 0.1, 95% CI 0-0.55, p=0.016). PTPN2_rs1893217 CC was associated with a lower risk of having joints with LOM (OR 0.2, 95% CI 0-0.99, p=0.026), while VTCN1_rs2358820 GA was associated with uveitis (OR 3.5, 95% CI 1-12.1, p=0.029).Conclusion: This exploratory study, using a prospectively followed JIA cohort, found significant associations between long-term outcome and SNPs, all previously associated with development of JIA and involved in immune regulation and signal transduction in immune cells.

The prognosis of autoimmune thyroid disease (AITD) including Graves' disease (GD) and Hashimoto's disease (HD) is difficult to predict. We previously suggested that Th17 cells may be associated with the pathogenesis of AITD. However, the association between gene polymorphisms in Th17-related genes and the prognosis of AITD was not clarified. To clarify this association, we genotyped 12 polymorphisms in 11 Th17-related genes (IL1Ra, IL6R, IL17R, IL21R, IL23R, CCR6, SOCS3, RORC, IL17A, IL17F and IL21) in 142HD patients including 58 patients with severe HD and 48 patients with mild HD, 170 patients with GD including 81 patients with intractable GD and 49 patients with GD in remission, and 84 healthy volunteers. The frequency of the IL17F rs763780 T allele was higher in patients with severe HD than in patients with mild HD (p=.008). The frequency of the IL17R rs9606615 T allele was higher in patients with HD than in normal subjects (p=.011). The frequencies of the SOCS3 rs4969170 AA genotype, CCR6 rs3093024 AA genotype, and IL21 rs907715 AA genotype were higher in patients with intractable GD than in patients with GD in remission (p=.035, p=.002 and p=.030, respectively). In conclusion, IL17R rs9607715 and IL17F rs763780 polymorphisms are associated with the susceptibility and severity of HD, respectively. IL21 rs907715, SOCS3 rs4969170 and CCR6 rs3093024 polymorphisms are associated with the intractability of GD.