Resumen de HLA Risk Haplotype: Insulin Deficiency in Pediatric Type 1 Diabetes
Rita Angélica Gómez Díaz, Elisa Nishimura Meguro, Eulalia Garrido Magaña, Lorena Lizárraga Paulin, Blanca E. Aguilar Herrera, Vilma Carolina Bekker Méndez, Roberto Medina Santillán, Rodrigo Barquera Lozano, Rafael Mondragón González, Niels H. Wacher Rodarte
Background: Certain HLA class II haplotypes have long been related with the risk of developing type 1 diabetes. The presence of the HLA haplotype DRB1*04/DQA1*03/DQB1*03:02, together with specific β-cell autoantibodies, contributes to the development and/or severity of insulin deficiency in type 1 diabetes. Objective: To evaluate the association of HLA risk haplotype HLA-DRB1/-DQA1/-DQB1 with β-cell function and antibody markers in recent-onset type 1 diabetes patients, their siblings, and controls. Methods: We studied recently diagnosed type 1 diabetes pediatric patients, their siblings, and healthy controls, analyzing autoantibodies (anti-glutamic acid decarboxylase, anti-IA-2, and anti-insulin), HLA risk and protector haplotypes, and β-cell function (plasma proinsulin, insulin and C-peptide). X2, ANOVA or Kruskal-Wallis and multiple logistic regression were used to analyze data. Results: We included 46 patients, 72 siblings, and 160 controls. Prevalence of anti-tyrosine phosphatase-related islet antigen 2 and anti-glutamic acid decarboxylase antibodies was higher in patients than siblings and controls. We found risk haplotype DRB1*04/DQA1*03/DQB1*03:02 in 95.7% of patients vs. 51.87% of controls; DRB1*03:01/DQA1*05/DQB1*02 in 47.8% of patients vs. 8.12% of controls; and DRB1*14/DQA1*05/DQB1*03:01 in 2.2% of patients vs. 20.0% of controls.
With DRB1*04/DQA1*03/DQB1*03:02, the prevalence of antibodies was significantly higher in patients, although not within any single group. In regression model based on insulin secretion, only anti-tyrosine phosphatase-related islet antigen 2 antibodies and age were associated with the risk haplotype. Conclusions: The DRB1*04/DQA1*03/DQB1*03:02 haplotype increased the risk for lower insulin, proinsulin, and C-peptide concentrations, suggesting an association with the severity of insulin deficiency in type 1 diabetes patients. This haplotype, added to antibody positivity, is a predictor of deficient insulin secretion in a Mexican pediatric population. (REV INVES CLIN. 2016;68:128-36)
