A126: Clusters of Autoimmune Diseases in Children and the Role of PTPN22 C1858T Gene Polymorphism in Pediatric Polyautoimmunity

Background/Purpose: Autoimmune diseases (AIDs) have familial aggregation and frequently share a common genetic background, but few studies have evaluated autoimmune clusters in children with AIDs and their families. Children with more than one AID (pediatric polyautoimmunity) may have a stronger genetic component than children with a single AID. The objectives of this study were to identify clusters of AIDs in children and their first‐degree relatives and to evaluate the association of PTPN22 C1858T gene polymorphism with pediatric polyautoimmunity. Methods: A cross‐sectional study was performed in subjects with an AID of pediatric onset (<18 years)recruited at Pediatric Rheumatology, Endocrinology and Gastroenterology Clinics at the Health Network of the Pontificia Universidad Católica de Chile School of Medicine. Clusters of AIDs were identified by K‐means cluster analysis. The PTPN22 C1858T gene polymorphism was determined by RT‐PCR in subjects with pediatric polyautoimmunity and in subjects with three common AIDs: juvenile idiopathic arthritis (JIA), autoimmune thyroid disease (AITD), and type I diabetes (T1D). Results: 191 subjects with pediatric AIDs were included, of which 45 (24%) had polyautoimmunity. Mean age was 12.1 years (range 1–19) and 68% were female. Most frequent AIDs were JIA (36%), AITD (25%), T1D (19%), uveitis (8%), celiac disease (6%), and vitiligo (6%). 59% of subjects with pediatric autoimmunity had first‐degree relatives with an AID. Five clusters of AID were identified in families of children with autoimmunity (Table ). Among the 45 subjects with pediatric polyautoimmunity, four clusters of AIDs were identified (Table ). Genomic DNA from 128 subjects was evaluated for PTPN22 C1858T gene polymorphism revealing common homozygosity (C/C) in 85.2%, heterozygosity (C/T) in 13.3%, and rare homozygosity (T/T) in 1.6 %, in equilibrium with Hardy Weinberg equation ( P = 0.4). 26% of polyautoimmune subjects had the T allele in contrast with 11% of monoautoimmune subjects ( P = 0.04). No significant difference was found in the age of onset of autoimmunity between mono and polyautoimmune subjects ( P = 0.44) or between subjects with C/C genotype vs. C/T and T/T genotypes ( P = 0.81). Clusters of autoimmune diseases among children with autoimmunity and their first‐degree relativesCluster Number of cases Autoimmune diseases (Descending order of relevance)1 94 Juvenile idiopathic arthritisConnective tissue diseasesAutoimmune thyroid disease2 29 Juvenile idiopathic arthritisPsoriasis3 31 Type I diabetesAutoimmune thyroid diseaseCeliac diseasePsoriasis4 25 Autoimmune thyroid diseaseType I diabetesVitiligoConnective tissue diseases5 10 Celiac diseaseAutoimmune thyroid diseaseType I diabetesAutoimmune hepatitisJuvenile idiopathic arthritisClusters of autoimmune diseases among children with pediatric polyautoimmunityCluster Number of cases Autoimmune diseases (Descending order of relevance)1 4 Connective tissue diseasesAutoimmune thyroid diseaseJuvenile idiopathic arthritis2 11 Type I diabetesAutoimmune thyroid diseaseCeliac diseaseInflammatory bowel diseaseImmune thrombocytopenic purpura3 10 Autoimmune thyroid diseaseVitiligoJuvenile idiopathic arthritisCeliac diseaseScleroderma4 18 Juvenile idiopathic arthritisUveitisPsoriasisVitiligoAlopecia AreataAutoimmune HepatitisConclusion: AIDs in affected children and their families may be grouped into well defined clusters suggesting a common etiopathogenesis among diseases grouped in each cluster. This is the first study to show a higher prevalence of the PTPN22 C1858T polymorphism in pediatric polyautoimmunity, suggesting that this variant may be a risk factor for polyautoimmunity in children with AID.