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

Pinto, Paulo Daniel Araújo; Parasannanavar, Devaraj; Ghosh, Kanjaksha; Shetty, Shrimati

doi:10.1111/tan.12364

Cited by 5 publications

(3 citation statements)

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“…A previously reported study from India in severe haemophilia A (n = 119) did not find any association with any of the HLA alleles and risk of inhibitor formation . In contrast, our data suggest and increased risk of inhibitor formation with HLA DRB1*13 and this significance was retained in the high‐titre subset.…”

Section: Discussioncontrasting

confidence: 84%

Prevalence of FVIII inhibitors in severe haemophilia A patients: Effect of treatment and genetic factors in an Indian population

et al. 2018

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Introduction Factor replacement therapy in treatment of haemophilia A is complicated by the production of neutralising antibodies known as inhibitors. The formation of inhibitors is multifactorial being associated with both genetic and environmental factors. Aim To document the prevalence of inhibitors in severe haemophilia in the community where most patients receive only infrequent episodic replacement therapy and evaluate the factors which could be contributing to it. Methods Community based camps were conducted in different parts of the country. Patients were assessed through a structured questionnaire and blood samples were obtained for laboratory evaluation of inhibitors and defined immunological parameters. Results Inhibitors were present in 87/447 (19.5%) of the evaluated patients. High‐titre inhibitor (>5 Bethesda Units [BU]) was identified in 31 (35.6%) patients. HLA DRB1‐13‐positive cases (RR = 2.04; 95% CI 1.06‐3.911; P = 0.033) had an increased risk of inhibitor formation which was retained in the high‐titre subset. A decreased risk of inhibitor formation was noted with heterozygous IL4‐590 C/T allele (RR = 0.22; 95% CI 0.108‐0.442: P = 0.000). There were no significant correlations between any of the evaluated environmental factors and the development of inhibitors in this study. Conclusion The overall prevalence of inhibitors in patients with severe haemophilia A is similar to that reported among patients receiving regular replacement therapy. The data from this study, limited by its retrospective and cross‐sectional study design, would suggest that genetic rather than environmental are more likely to impact the development of inhibitors.

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Section: Discussioncontrasting

confidence: 84%

Prevalence of FVIII inhibitors in severe haemophilia A patients: Effect of treatment and genetic factors in an Indian population

et al. 2018

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“…Overall, in this study, with regard to the HLA-DRB1*03 allele (P-value 0.3048; OR 0.2857; 95% CI 0.03590-2.274), earlier found to be protective with regard to FVIII inhibitors [24], and with regard to the IL10 GCC haplotypes (P-value 0.8223; OR 0.8529; 95% CI 0.3430-2.121) earlier found to be a risk factor [23], in Indian congenital HA patients, there was no significant difference between those who developed antinuclear antibodies and those who did not.…”

Section: Discussionmentioning

confidence: 79%

“…immune response polymorphisms, HLA genotypes, F8 inversions & causative mutations were also analysed in the severe haemophilia A patients using a variety of molecular typing assays (PCR, RFLP-PAGE, DNA sequencing, HLA-SSP typing, CSGE, MLPA) described earlier [23][24][25][26]. These were correlated with non-genetic risk factors such as the treatment-related risk factors from the details available in the clinical proforma of the patients.…”

Section: Investigationsmentioning

confidence: 99%

Antibody profile in Indian severe haemophilia A patients with and without FVIII inhibitors

et al. 2016

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F8 gene mutation profile in Indian hemophilia A patients: Identification of 23 novel mutations and factor VIII inhibitor risk association

Pinto

Ghosh

Shetty

2016

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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

Cited by 5 publications

References 15 publications

Prevalence of FVIII inhibitors in severe haemophilia A patients: Effect of treatment and genetic factors in an Indian population

Prevalence of FVIII inhibitors in severe haemophilia A patients: Effect of treatment and genetic factors in an Indian population

Antibody profile in Indian severe haemophilia A patients with and without FVIII inhibitors

F8 gene mutation profile in Indian hemophilia A patients: Identification of 23 novel mutations and factor VIII inhibitor risk association

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