title: High prevalence of diabetes-specific autoimmunity in first-degree relatives of Sardinian patients with type 1 diabetes.
abstract: The incidence of type 1 diabetes mellitus (T1DM) in Sardinia is among the highest in the world (44.8 cases/100,000 person-years). Recommendations of the Immunology of Diabetes Society advise evaluating autoantibody positivity in first-degree relatives (FDRs) of patients with T1DM, for their higher risk to develop the disease. The aim of this study was to determine the prevalence of beta-cell autoimmunity in FDRs of T1DM patients in Sardinia.
  
  
  
  A total of 188 Sardinian families were recruited in collaboration between diabetes and pediatric units of university and district hospitals in Sardinia. The recruitment involved 188 patients with diagnosed T1DM and all their available FDRs (n = 447). Autoantibodies (Aabs) against GAD, IA2, insulin, and ZnT8 were measured in all subjects. Human leukocyte antigen (HLA) risk genotypes (HLA-DR and DQ loci) were analyzed in 43 Aabs-positive FDR.
  
  
  
  The prevalence of Aabs (any type of autoantibody, single or multiple) in FDR was 11.9% (53/447). Of those with autoantibodies, 62.3% (33/53) were positive to only 1 autoantibody, 22.6% (12/53) had 2 autoantibodies, 7.55% (4/53) had 3 autoantibodies, and 7.55% (4/53) had all 4 autoantibodies. Typing of HLA-DR and DQ loci showed that 89% of FDR carried moderate- to high-risk genotypes, with only 5 FDR with low-risk genotypes.
  
  
  
  The prevalence of T1DM autoantibodies in FDRs of T1DM patients was very high (11.9%) in the Sardinian population, higher than in other populations from the United States and Europe, and similar to that observed in Finland. Autoantibody positivity strongly associated with HLA risk. This study provides evidence of the high risk of T1DM in FDR of T1DM patients in Sardinia and warrants longitudinal follow-up to estimate the risk of progression to T1DM in high-risk populations.
authors.affiliation: Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Incani
authors.affiliation: Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Serafini
authors.affiliation: Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Satta
authors.affiliation: Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Perra
authors.affiliation: Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Scano
authors.affiliation: Paediatric Unit, San Michele Hospital, Cagliari, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Frongia
authors.affiliation: Paediatric Unit, San Michele Hospital, Cagliari, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Ricciardi
authors.affiliation: Diabetes Paediatric Unit, San Michele Hospital, Cagliari, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Ripoli
authors.affiliation: Paediatric Unit, San Martino Hospital, Oristano, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Soro
authors.affiliation: Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Strazzera
authors.affiliation: Endocrinology, Department Experimental Medicine, Sapienza University of Rome, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Zampetti
authors.affiliation: Endocrinology, Department Experimental Medicine, Sapienza University of Rome, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Buzzetti
authors.affiliation: Internal Medicine Unit, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Italy.
authors.forename: M G
authors.initials: MG
authors.lastname: Cavallo
authors.affiliation: Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Cossu
authors.affiliation: Endocrinology and Diabetes, Department of Medical Sciences, University of Cagliari, Italy.|Endocrinology, Department Experimental Medicine, Sapienza University of Rome, Italy.
authors.forename: M G
authors.identifier: 0000-0002-3224-6078
authors.initials: MG
authors.lastname: Baroni
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D005190:Family; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D007558:Italy / Q000453:epidemiology; D008297:Male; D015995:Prevalence; D011379:Prognosis; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens
keywords: HLA risk; Sardinia; Type 1 diabetes mellitus; autoantibodies; first-degree relatives