Norma C Segovia-Gamboa1, Martha E Rodríguez-Arellano2, Andrés Muñoz-Solís3, Jorge E Retana-Jiménez4, Germán Vargas-Ayala5, Julio Granados6, Marisela Jiménez-Sánchez3, Carmen Sanchez-Torres7. 1. Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del I.P.N. (CINVESTAV-IPN), Av. I.P.N. 2508, San Pedro Zacatenco, 07360, Mexico City, Mexico. 2. Research Department, Hospital Regional "Licenciado Adolfo López Mateos", ISSSTE, Av. Universidad 1321, Florida, 01030, Mexico City, Mexico. 3. Endocrinology Department, Hospital de Especialidades "Antonio Fraga Mouret", Centro Médico nacional "La Raza" (IMSS), Paseo de las Jacarandas S/N, Atzcapotzalco, 02990, Mexico City, Mexico. 4. Pediatrics Department, Hospital Regional "Licenciado Adolfo López Mateos", ISSSTE, Av. Universidad 1321, Florida, 01030, Mexico City, Mexico. 5. Department of Internal Medicine, Ticoman General Hospital, Plan de San Luis S/N, La Purísima Ticoman, 07330, Mexico City, Mexico. 6. Division of Immunogenetics, Department of Transplantation, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Vasco de Quiroga 15, Tlalpan, 14080, Mexico City, Mexico. 7. Department of Molecular Biomedicine, Centro de Investigación y de Estudios Avanzados del I.P.N. (CINVESTAV-IPN), Av. I.P.N. 2508, San Pedro Zacatenco, 07360, Mexico City, Mexico. csanchez@cinvestav.mx.
Abstract
AIMS: To assess the prevalence of autoantibodies (Aab) to insulin (IAA), glutamic acid decarboxylase 65 (GADA) and insulinoma antigen 2 (IA-2A), as well as human leukocyte antigen (HLA) class II alleles, in first degree relatives (FDR) of Mexican patients with type 1 diabetes (T1D), and to explore whether these parameters mirror the low incidence of T1D in the Mexican population. METHODS: Aab titers were determined by ELISA in 425 FDR, 234 siblings, 40 offspring and 151 parents of 197 patients with T1D. Typing of HLA-DR and -DQ alleles was performed in 41 Aab-positive FDR using polymerase chain reaction with allele-specific oligotyping. RESULTS: Seventy FDR (16.47%) tested positive for Aab. The siblings (19.2%) and the offspring (25%) had significantly higher prevalence of Aab than the parents (9.9%). GADA was the most frequent Aab. Almost half of the Aab-positive FDR had two different Aab (45.7%), and none tested positive for three Aab. The highest prevalence of Aab was found among women in the 15-29 years age group. Moreover, the positivity for two Aab was significantly more frequent among females. A considerable number of FDR (48.8%) carried the susceptible HLA-DR3, -DR4, -DQB1*0201 or -DQB1*0302 alleles, but almost none had the high risk genotype HLA-DR3/DR4. CONCLUSIONS: FDR of Mexican T1D patients have high prevalence of islet Aab, comparable to countries with the highest incidence of T1D. However, Aab positivity does not seem to be associated with HLA risk genotypes, which may have an impact on the low incidence of T1D in Mexico.
AIMS: To assess the prevalence of autoantibodies (Aab) to insulin (IAA), glutamic acid decarboxylase 65 (GADA) and insulinoma antigen 2 (IA-2A), as well as human leukocyte antigen (HLA) class II alleles, in first degree relatives (FDR) of Mexican patients with type 1 diabetes (T1D), and to explore whether these parameters mirror the low incidence of T1D in the Mexican population. METHODS: Aab titers were determined by ELISA in 425 FDR, 234 siblings, 40 offspring and 151 parents of 197 patients with T1D. Typing of HLA-DR and -DQ alleles was performed in 41 Aab-positive FDR using polymerase chain reaction with allele-specific oligotyping. RESULTS: Seventy FDR (16.47%) tested positive for Aab. The siblings (19.2%) and the offspring (25%) had significantly higher prevalence of Aab than the parents (9.9%). GADA was the most frequent Aab. Almost half of the Aab-positive FDR had two different Aab (45.7%), and none tested positive for three Aab. The highest prevalence of Aab was found among women in the 15-29 years age group. Moreover, the positivity for two Aab was significantly more frequent among females. A considerable number of FDR (48.8%) carried the susceptible HLA-DR3, -DR4, -DQB1*0201 or -DQB1*0302 alleles, but almost none had the high risk genotype HLA-DR3/DR4. CONCLUSIONS: FDR of Mexican T1D patients have high prevalence of islet Aab, comparable to countries with the highest incidence of T1D. However, Aab positivity does not seem to be associated with HLA risk genotypes, which may have an impact on the low incidence of T1D in Mexico.
Entities:
Keywords:
Autoantibodies; HLA risk genotypes; Patient relatives; Type 1 diabetes
Authors: S Lozano-Esparza; R López-Ridaura; E Ortiz-Panozo; C González-Villalpando; C Aguilar-Salinas; J E Hernández-Ávila; M Hernández-Ávila; M Lajous Journal: Diabetes Metab Date: 2019-09-13 Impact factor: 6.041