The contribution of IL‐1A gene variants to inflammatory burden or disease severity in ankylosing spondylitis: APLAR 2018 Conference Taiwan

Background: IL‐1alpha (IL‐1A) is a master cytokine that induces TNF and IL‐6 as well as acute phase proteins. Variations in the IL‐1A gene increase the risk for Ankylosing Spondylitis (AS), but the process underlying this association is not fully understood. AS is a chronic condition primarily affecting the spinal joints. We investigated the influence of IL‐1A gene susceptibility variants (rs2856836, rs17561, and rs1894399) on cytokine profiles, inflammatory markers and disease severity in AS. Method: Cross sectional study of TNFi naïve AS patients (n = 334, 90 % B27 +, age 45 years) fulfilling modified NY criteria. We recorded demographics, clinical findings, spinal mobility, Bath AS Functional Index (BASFI), and routine lab findings. IL‐1A genotyping was by Taqman RT‐PCR and TNF, IL6, IL17A and IL23 determination by sandwich ELISA. Genotypic associations included logistic regression analysis for genotype (codominant model) and global haplotype (threshold 5%) associations with cytokine levels and clinical features. Result: The three variants formed two only common haplotypes (ACC 67%, GAT 33%). There were no differences in levels for TNF, IL6, IL17A, IL23, CRP or ESR across genotypes and haplotypes (all P values >0.4) nor for the measures for lumbar flexion, occiput wall distance and BASFI. Extraspinal complications were not associated with IL1A variants, regardless of HLA B27 status. Conclusion: Allel and genotype distribution were not different from 1000 genes data. While these IL‐1A variants contribute to disease susceptibility, they have no direct genotypic or haplotype impact on IL‐6, TNF, acute phase proteins or spinal function in patients with established AS.