High prevalence of humoral autoimmunity in first-degree relatives of Mexican type 1 diabetes patients
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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.
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.
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.
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.
KeywordsType 1 diabetes Patient relatives Autoantibodies HLA risk genotypes
We gratefully acknowledge the support of the relatives of T1D patients who participated in the study. We are grateful for the assistance of the Endocrinology Unit staff at the Hospital de Especialidades “Antonio Fraga Mouret” (IMSS) and of María Díaz Martínez (Hospital Regional “Licenciado Adolfo López Mateos”, ISSSTE) for her help in the performance of laboratory tests. We also thank Julio C. Ramírez for technical assistance, and Ms. Ninfa Arreola for her aid in the preparation of the manuscript, both from CINVESTAV-IPN.
MERA, AMS, GVA, and MJS recruited donors and performed laboratory test. NCSG and JERJ carried out autoantibody measurement. JG and MERA performed and analyzed the HLA typing assays. CST designed the study, analyzed the data, and wrote the manuscript.
This study was supported by a grant to C. Sánchez-Torres from Fondo Sectorial de Investigación en Salud y Seguridad Social (SS/IMSS/ISSSTE-CONACYT, no. 233290), Mexico.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Statement of human and animal rights
The study was approved by the Bioethics Committee of CINVESTAV-IPN (017/2014), by the Ethics Committee of the Hospital Regional “Licenciado Adolfo López Mateos” (526.2016), and by the IMSS National Committee of Scientific Research (R-2015-785-044), and conducted in conformance with the Helsinki Declaration.
Statement of informed consent
Informed consent was obtained from each participant or from its parents/legal guardians (when applied) included in the study.
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