A126: Clusters of Autoimmune Diseases in Children and the Role of PTPN22 C1858T Gene Polymorphism in Pediatric Polyautoimmunity
Authors: Borzutzky Arturo , Seiltgens Cristián , Iruretagoyena Mirentxu , Cristi Francisca , Ponce María Jesús , Melendez Patricia , Martinez‐Aguayo Alejandro , Hodgson María Isabel , Talesnik Eduardo , Riera Francisca , Méndez Cecilia , Harris Paul R. , García Hernán , Gana Juan Cristobal , Godoy Claudia , Cattani Andreina 
Published: March 2014

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 relatives

Cluster
Number of cases
Autoimmune diseases (Descending order of relevance)

1
94
Juvenile idiopathic arthritis

Connective tissue diseases

Autoimmune thyroid disease

2
29
Juvenile idiopathic arthritis

Psoriasis

3
31
Type I diabetes

Autoimmune thyroid disease

Celiac disease

Psoriasis

4
25
Autoimmune thyroid disease

Type I diabetes

Vitiligo

Connective tissue diseases

5
10
Celiac disease

Autoimmune thyroid disease

Type I diabetes

Autoimmune hepatitis

Juvenile idiopathic arthritis
Clusters of autoimmune diseases among children with pediatric polyautoimmunity

Cluster
Number of cases
Autoimmune diseases (Descending order of relevance)

1
4
Connective tissue diseases

Autoimmune thyroid disease

Juvenile idiopathic arthritis

2
11
Type I diabetes

Autoimmune thyroid disease

Celiac disease

Inflammatory bowel disease

Immune thrombocytopenic purpura

3
10
Autoimmune thyroid disease

Vitiligo

Juvenile idiopathic arthritis

Celiac disease

Scleroderma

4
18
Juvenile idiopathic arthritis

Uveitis

Psoriasis

Vitiligo

Alopecia Areata

Autoimmune 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.