Session Title: Pediatric Rheumatology – Pathogenesis and Genetics Poster
Session Type: ACR Poster Session C
Session Time: 9:00AM-11:00AM
Background/Purpose: Immunoglobulin-A (IgA) vasculitis, also known as Henoch-Schöenlein purpura (HSP), is the most common type of primary small-sized blood vessel leukocytoclastic vasculitis in children, although it may also develop in adults . IgA vasculitis has a multifactorial etiology in which both environmental and genetic factors seem to contribute to the predisposition and clinical phenotype of the disease [1,2]. However, the genetic component of this type of vasculitis remains poorly understood, as only a few candidate gene studies have been performed to date [3,4]. Taking these considerations into account, and to increase the current knowledge on the genetic component of this vasculitis, we performed the first genome-wide association study (GWAS) on this condition using the largest series of IgAV patients of European ancestry ever assessed for a genetic study.
Methods: 308 IgA vasculitis patients and 1,018 healthy controls from Spain were genotyped by Illumina HumanCore BeadChips. Imputation of GWAS data was performed using the 1000 Genomes Project Phase III dataset as reference panel . After quality control filters and GWAS imputation, 285 patients and 1,006 controls remained in the datasets and were included in further analysis. Additionally, the human leukocyte antigen (HLA) region was comprehensively studied by imputing classical alleles and polymorphic amino acid positions .
Results: A linkage disequilibrium block of polymorphisms located in the HLA class II region surpassed the genome-wide level of significance (odds ratio = 0.56, 95% confidence intervals = 0.46-0.68). Although no polymorphic amino acid positions were associated at the genome-wide level of significance, P-values of potential relevance were observed for the positions 13 and 11 of HLA-DRB1 (P = 6.67E-05, P = 1.88E-05, respectively). Outside the HLA, potential associations were detected, but none of them were close to the statistical significance.
Conclusion: Our study suggests that IgA vasculitis is an archetypal HLA class II disease.
 Gonzalez-Gay et al. Rheum Dis Clin North Am 2001, 27:729-49;  Wyatt et al. N Engl J Med 2013, 368:2402-14;  López-Mejías et al. Arthritis Res Ther 2015,17:102;  López-Mejías et al. Arthritis Rheumatol 2014;67:823-7;  Howie et al. PLoSGenet 2009;5: e1000529.  Carmona et al. Am J Hum Genet 2015;96:565-80.
This study is supported by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” (grant PI12/00193) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). RL-M is supported by the Miguel Servet I programme of the Spanish Ministry of Economy and Competitiveness through the grant CP16/00033. SR-M is supported by funds from the RETICS Program (RIER) (RD16/0012/0009). FG is recipient of a Sara Borrell postdoctoral fellowship from the “Instituto Carlos III de Salud” at the Spanish Ministry of Health (Spain) (CD15/00095). FDC is supported by the Ramón y Cajal programme of the Spanish Ministry of Economy and Competitiveness through the grant RYC-2014-16458.
To cite this abstract in AMA style:López-Mejías R, Remuzgo-Martínez S, Genre F, Carmona FD, Castañeda S, Sevilla Pérez B, Ortego Centeno N, Llorca J, Ubilla B, Mijares V, Pina T, Miranda-Filloy JA, Navas Parejo A, Argila D, Aragües M, Rubio-Romero E, Leon Luque M, Blanco Madrigal JM, Galindez-Agirregoikoa E, Jayne D, Blanco R, Martin J, González-Gay MA. A Genome-Wide Association Study Suggests the HLA Class II Region As the Major Susceptibility Locus for IgA Vasculitis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/a-genome-wide-association-study-suggests-the-hla-class-ii-region-as-the-major-susceptibility-locus-for-iga-vasculitis/. Accessed August 12, 2020.
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