A120: Familial Autoimmunity in the CARRA Registry

Abstract

Background/Purpose: Autoimmune disorders affect 5 to 10% of the population. Clinically distinct autoimmune phenotypes often share genetic susceptibility factors. Relatives of children with juvenile idiopathic arthritis (JIA) have increased prevalence of autoimmunity. We sought to investigate the prevalence of familial autoimmunity among subjects with JIA, systemic lupus erythematosus (SLE) and juvenile dermatomyositis (JDM) in the CARRA Registry, the largest multicenter observational Registry for pediatric rheumatic disease. Methods: Children with JIA, SLE and JDM from pediatric rheumatology clinics in the US were enrolled in the CARRA Registry between May 2010 and May 2013. Demographic and disease-related data were collected from time of diagnosis to enrollment visit. We compared if subjects with JIA, SLE and JDM had different proportions of autoimmunity among first-degree relatives (FDR) using Chi-square tests. If a significant difference was detected, pairwise comparisons, adjusted for multiple comparisons, were made using a significance level of 0.017. Results: The sample consisted of 4677 JIA, 639 SLE and 440 JDM subjects. The proportion of subjects having FDR with any autoimmune disease in the JDM group (20.5%) was significantly less compared to subjects with JIA (31.8%, p < 0.001) or SLE (31.9%; p < 0.001). Compared to subjects with JDM, subjects with JIA had a greater proportion of FDR with JIA (p < 0.001), and RA (p = 0.002), and compared to subjects with SLE, those with JIA had a significantly greater proportion of FDR with psoriasis (p < 0.001), JIA (p = 0.001), ankylosing spondylitis (p = 0.016), Crohn's disease/ulcerative colitis (p = 0.002), and autoimmune thyroiditis (p = 0.005). Compared to those with JIA, subjects with SLE had a significantly higher proportion of FDR with SLE (p < 0.001) and type-I diabetes (p < 0.001), and compared to subjects with JDM, those with SLE had a significantly higher proportion of FDR with SLE (p < 0.001), RA (p = 0.003), and type-I diabetes (p < 0.001).1 Table 1. Comparison of familial autoimmunity among subjects with JIA, SLE and JDM Disease Group Family History of Disease JIA N = 4,677 SLE N = 639 JDM N = 440 P-value a All values expressed as percentages. b Significantly different from JIA (p < 0.017) c Significantly different from SLE (p < 0.017) Any autoimmune diseases 31.8 31.9 20.5b, c < 0.001 Inflammatory Arthritis-AS, SpA, JIA, RA 13.0 9.2b 4.3b, c < 0.001 - Ankylosing spondylitis 1.3 0.2b 0.5 0.014 - Spondyloarthopathy 0.8 0.0 0.0 0.015 - JIA 5.2 2.2b 0.9b < 0.001 - RA 7.3 7.8 3.4b, c 0.007 SLE 1.7 11.1b 1.1c < 0.001 Psoriasis 8.0 2.5b 5.0 < 0.001 Crohn's disease or ulcerative colitis 2.7 0.6b 1.1 0.002 Multiple Sclerosis 1.0 1.1 1.1 0.905 Autoimmune thyroiditis 5.3 2.7b 5.5 0.015 Celiac disease 0.8 0.8 1.4 0.439 Type 1 Diabetes 3.1 7.4b 3.0c < 0.001 Other autoimmune 4.6 5.0 4.6 0.893 Conclusion: Children with AAV had predominantly renal and constitutional manifestations. Younger age and a more severe renal disease phenotype may characterize MPA with patients requiring additional treatment for the consequences of kidney disease. The wide variations in time to diagnosis continue to suggest that pediatric AAV is poorly recognized. Ongoing biomarker-driven studies may complement systems for subclassifying patients with AAV.