title: Certain HLA alleles are associated with stress-triggered Graves' disease and influence its course.
abstract: There are no studies on HLA analysis in patients in whom Graves' disease (GD) hyperthyroidism has been preceded by ≥1 stressful event. The aim of the present study was to identify predisposing or protecting HLA alleles and their effects on the course of GD in this subset of patients. We performed serological HLA typing in 58 Caucasian patients with stress-related GD and in 130 matched healthy controls (HC). We also performed genomic HLA typing in 20/58 patients and in all HC. Five HLA alleles and three loci were more frequent in patients compared to HC: B8, Cw7, C*07, C*17, DR3, DR4, DRB1*04, and DQ2. In contrast, B14 was less frequent in patients than in HC. Depending on outcome after ATD withdrawal (remission, exacerbation on-ATD, relapse off-ATD), in patients, some alleles/loci were over-represented, while others were under-represented. Age, FT3, and FT4 fold increase over the upper normal limit at onset were different depending on the allele/locus carried. In GD patients with stress-triggered hyperthyroidism, HLA typing may be helpful in predicting the outcome of the disease after ATD withdrawal.
authors.affiliation: Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi, Padiglione H, 4 piano, 98125, Messina, Italy. roberto.vita@yahoo.it.
authors.forename: Roberto
authors.identifier: http://orcid.org/0000-0002-5977-3062
authors.initials: R
authors.lastname: Vita
authors.affiliation: Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi, Padiglione H, 4 piano, 98125, Messina, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lapa
authors.affiliation: Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi, Padiglione H, 4 piano, 98125, Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Trimarchi
authors.affiliation: Department of Biomedical Sciences and Images, University of Messina, Messina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vita
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy.
authors.forename: Poupak
authors.initials: P
authors.lastname: Fallahi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Antonelli
authors.affiliation: Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Viale Gazzi, Padiglione H, 4 piano, 98125, Messina, Italy.|Master Program on Childhood, Adolescent and Women's Endocrine Health, University of Messina School of Medicine, Messina, Italy.|Interdepartmental Program of Molecular and Clinical Endocrinology, and Women's Endocrine Health, University Hospital Policlinico G. Martino, Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Benvenga
mesh_terms: D017668:Age of Onset; D000483:Alleles; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D056426:Genetic Loci; D006111:Graves Disease / Q000097:blood / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D006680:HLA Antigens / Q000097:blood / Q000235:genetics*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013312:Stress, Physiological; D013315:Stress, Psychological / Q000503:physiopathology*; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D015854:Up-Regulation
chemical_list: D006680:HLA Antigens; D014284:Triiodothyronine; D013974:Thyroxine
keywords: Autoimmunity; Graves’ disease; HLA; Stress