This study aims to establish the association between HLA class II alleles and the presence of Neuromyelitis Optica Spectrum Disorder (NMOSD) in a Colombian population

A multicenter case-control study was conducted with NMOSD patients diagnosed with the 2015 Wingerchuk criteria, recruited between 2020 and 2023 from Bogotá and Medellín, Colombia. Controls, without demyelinating or autoimmune diseases, were recruited from the same cities as were the cases. Blood samples from both groups were analyzed to identify HLA-DRB1 and HLA-DQB1 alleles using sequence-specific primer polymerase chain reaction (SSP-PCR). The mitochondrial hypervariable region 1 was amplified, and haplogroups were determined with HaploGrep software. Genomic ancestry was estimated by genotyping ancestry-informative markers. Logistic regression models assessed associations between HLA polymorphisms and NMOSD.

A total of 82 patients with NMOSD (mean age 43.8 ± 13.3 years; 83% females) and 164 controls (mean age 36.4 ± 11.5 years; 85% females) were enrolled. Mitochondrial haplogroup frequencies were similar between groups, indicating comparable genetic backgrounds. Ancestry analysis revealed distinct population structures. In multivariate logistic regression, the HLA-DQB1*04 allele was significantly associated with increased NMOSD risk (OR = 3.16, CI: 1.58-6.34, p < 0.0023), while the HLA-DQB1*03 allele was associated with a protective effect (OR = 0.23, CI: 0.12-0.46, p < 0.0023).

This study provides new insights into the genetic characterization of NMOSD in Colombia. Our findings suggest that HLA-DQB1*04 allele confers susceptibility to NMOSD, while DQB1*03 allele may exert a protective effect in our population. The notable disparities in African ancestry contribution between patients and controls underscore the importance of considering ethnic diversity in elucidating NMOSD susceptibility.