Differential Frequencies of HLA-DRB1, DQA1, and DQB1 Alleles and Haplotypes Are Observed in the Arbovirus-Related Neurological Syndromes

Background. We took advantage of the 2015-2016 Brazilian arbovirus outbreak (Zika [ZIKV]/dengue/chikungunya viruses) associated with neurological complications to type HLA-DRB1/DQA1/DQB1 variants in patients exhibiting neurological complications and in bone marrow donors from the same endemic geographical region. Methods. DRB1/DQA1/DQB1 loci were typed using sequence-specific oligonucleotides. In silico studies were performed using X-ray resolved dimer constructions. Results. The DQA1*01, DQA1*05, DQB1*02, or DQB1*06 genotypes/haplotypes and DQA1/DQB1 haplotypes that encode the putative DQA1/DQB1 dimers were overrepresented in the whole group of patients and in patients exhibiting peripheral neurological spectrum disorders (PSD) or encephalitis spectrum disorders (ESD). The DRB1*04, DRB1*13, and DQA1*03 allele groups protected against arbovirus neurological manifestation, being underrepresented in whole group of patients and ESD and PSD groups. Genetic and in silico studies revealed that DQA1/DQB1 dimers (1) were primarily associated with susceptibility to arbovirus infections; (2) can bind to a broad range of ZIKV peptides (235 of 1878 peptides, primarily prM and NS2A); and (3) exhibited hydrophilic and highly positively charged grooves when compared to the DRA1/DRB1 cleft. The protective dimer (DRA1/DRB1*04) bound a limited number of ZIKV peptides (40 of 1878 peptides, primarily prM). Conclusion. Protective haplotypes may recognize arbovirus peptides more specifically than susceptible haplotypes.

Automated summary

The study found that specific HLA-DRB1/DQA1/DQB1 genotypes/haplotypes were overrepresented in patients exhibiting neurological complications during the Brazilian 2015-2016 arbovirus outbreak. Certain allele groups were also identified to have a protective effect against arbovirus neurological manifestation, being underrepresented in both the whole group of patients and in patients with peripheral neurological spectrum disorders (PSD) or encephalitis spectrum disorders (ESD).