Resumen

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.

Palabras clave: HLA. Proinsulin. C-peptide. Mexican. Antibody.

2016-07-20   |   536 visitas   |   Evalua este artículo 0 valoraciones

Vol. 68 Núm.3. Mayo-Junio 2016 Pags. 128-136 Rev Invest Clin 2016; 68(3)