Association of HLA class II Alleles and the Occurrence of Factor VIII Inhibitor in Thai Patients with Hemophilia A

Abstract

Objective: This study aimed to investigate the association between HLA class II alleles and the occurrence of FVIIIinhibitor in Thai hemophilia A patients.Material and Methods: The distribution of HLA-DRB1 alleles and DQB1 alleles in 57 Thai hemophilia A patientsand 36 blood donors as controls was determined using the PCR sequence-specific primer (PCR-SSP) method, and theassociation between the occurrence of factor VIII (FVIII) inhibitor and the presence of certain HLA class II alleles wasinvestigated.Results: The frequency of HLA-DRB1*15 was higher in the hemophilia A patients with and without FVIII inhibitor,whereas that of DRB1*14, DRB1*07, and DQB1*02 was lower in the hemophilia A patients with FVIII inhibitor, ascompared to controls. Interestingly, only the frequency of DRB1*15 was significantly higher in the patients with inhibitorthan in the controls (P = 0.021). Moreover, the frequency of DRB1*15 in the patients with inhibitor was higher than inthose without inhibitor (P = 0.198).Conclusion: The study’s findings show that the DRB1*15 allele might have contributed to the occurrence of inhibitorin the Thai hemophilia A patients; however, additional research using larger samples and high-resolution DRB1 typingis warranted.

The association of HLA‐DRB1 and HLA‐DQB1 alleles with the development of factor VIII inhibitors in severe haemophilia A patients in India

“…This incidence is similar to that reported earlier in the normal Indian population . These alleles were not significantly associated with inhibitor development in Indian haemophiliacs, unlike the associations observed in the German ( DRB1*1501 , DQB1*06:02 , DRB1*15:01 / DQB1*06:02 haplotype significantly higher in inhibitor positive patients) and Thai ( DRB1 * 15 significantly higher in inhibitor patients) study groups .…”

“…FVIII administered to congenital severe HA patients acts as an exogenous antigen and triggers an immune response in patients, that involves the human leukocyte antigen (HLA) type II molecules, along with antigen‐presenting cells, T‐ and B‐ lymphocytes in the production of alloantibodies to FVIII. Considering this fact, and also that certain HLA type II DRB1‐ and DQB1‐ alleles especially were found to be significantly more frequent in certain populations , this study was undertaken. The aim was to analyse the frequency of HLA‐DRB1 and HLA‐DQB1 alleles in Indian severe HA patients with inhibitors, and compare it to those without inhibitors to examine if these HLA type II alleles could play a significant role in the differential immune response to FVIII replacement therapy, and predispose to inhibitor development.…”

Genome-Wide Association Study and Gene-Based Analysis of Participants With Hemophilia A and Inhibitors in the My Life, Our Future Research Repository

“…To our knowledge, we report for the first time an association with DQB1*03:03, which was only detectable after conditioning on DRB1*15:01. In addition to increased sample size, this may partly explain why association with this allele was not detected in previous studies ( 23 , 24 , 41 , 42 ). Nonetheless, this result will require replication in independent studies.…”

Importance of immune response genes in hemophilia A

“…One study of 57 hemophilia patients (with and without inhibitors) and 36 blood donors without the disease from Thailand found a higher frequency of the DRB1*15 allele in patients with inhibitors (30.6%) than in patients without inhibitors (19.2%). However, statistical significance was obtained only when the frequency of this allele was compared between patients with inhibitors and controls (30.6% vs. 13.9%; p-value = 0.021; OR = 0.021; 95% CI: 1.16-6.47) (41) .…”