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HLA-DRB1 alleles and juvenile idiopathic arthritis: Diagnostic clues emerging from a meta-analysis
Authors:Annalisa De Silvestri  Cristina Capittini  Dimitri Poddighe  Gian Luigi Marseglia  Luca Mascaretti  Elena Bevilacqua  Valeria Scotti  Chiara Rebuffi  Annamaria Pasi  Miryam Martinetti  Carmine Tinelli
Affiliation:1. Servizio di Epidemiologia Clinica e Biometria, Direzione Scientifica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;2. Dipartimento di Pediatria, Università degli Studi di Pavia, Italy;3. Laboratorio di Tipizzazione Tissutale, Dipartimento di Medicina Trasfusionale, Azienda Sanitaria Universitaria Integrata di Trieste;4. Servizio documentazione scientifica, DirezioneScientifica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;5. Laboratorio di Immunogenetica, Servizio diImmunoematologia e Trasfusione, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
Abstract:
Juvenile Idiopathic Arthritis (JIA) is characterized with a variable pattern of articular involvement and systemic symptoms and, thus, it has been classified in several subtypes. Genetic predisposition to JIA is mainly due to HLA class II molecules (HLA-DRB1, HLA-DPB1), although HLA class I molecules and non-HLA genes have been implicated, too. Here, we carried out a meta-analysis including selected studies designed to assess HLA genetic background of JIA patients, compared to healthy controls; particularly, we focused our attention on HLA-DRB1. In summary, our meta-analysis showed four main findings regarding HLA-DRB1 locus as a genetic factor of JIA: i) HLA-DRB1*08 is a strong factor predisposing to JIA, both for oligo-articular and poly-articular forms (oJIA > pJIA); ii) HLA-DRB1*01 and HLA-DRB1*04 may be involved in the genetic predisposition of Rheumatoid Factor (RF) positive forms of JIA; iii) HLA-DRB1*11 was confirmed to be predisposing to oligo-articular JIA; iv) HLA-DRB1*04 was confirmed to have a role in systemic JIA. Importantly, RF positivity seems to select the JIA clinical subset with the strongest immunogenetic similarities with adult rheumatoid arthritis.
Keywords:JIA  Juvenile Idiopathic Arthritis  RF  Rheumatoid Factor  ACR  American College of Rheumatology  EULAR  European League Against Rheumatism  ILAR  International League of Associations for Rheumatology  OR  Odds Ratio  HLA  Human Leukocyte Antigens  GWAS  Genome-Wide Association Studies  TNF  Tumor Necrosis Factor  IL  Interleukin  PTPN22  Protein Tyrosine Phosphatase, Non-receptor, type 22  MIF  Macrophage migration Inhibitory Factor  Juvenile idiopathic arthritis  HLA-DRB1  JIA classification  Meta-analysis
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