HLA association in MOG-IgG– and AQP4-IgG–related disorders of the CNS in the Dutch population

Abstract

ObjectiveTo investigate the possible human leukocyte antigen (HLA) association of both myelin oligodendrocyte glycoprotein (MOG-IgG)-associated diseases (MOGAD) and aquaporin-4 antibody (AQP4-IgG)-positive neuromyelitis optica spectrum disorders (NMOSDs) in the Dutch population with European ancestry to clarify similarities or differences in the immunogenetic background of both diseases.MethodsBlood samples from patients in the Dutch national MS/NMOSD expert clinic were tested for MOG-IgG and AQP4-IgG using a cell-based assay. HLA Class I and II genotyping was performed in 43 MOG-IgG–seropositive and 42 AQP4-IgG–seropositive Dutch patients with European ancestry and compared with those of 5,604 Dutch healthy blood donors.ResultsNo significant HLA association was found in MOG-IgG–seropositive patients. The AQP4-IgG–seropositive patients had a significant higher frequency of HLA-A*01 (61.9% vs 33.7%, OR 3.16, 95% CI, 1.707–5.863, p after correction [pc] = 0.0045), HLA-B*08 (61.9% vs 25.6%, OR 4.66, 95% CI, 2.513–8.643, pc < 0.0001), and HLA-DRB1*03 (51.2% vs 27.6%, OR 2.75, 95% CI, 1.495–5.042, pc = 0.0199) compared with controls.ConclusionsThe present study demonstrates differences in the immunogenetic background of MOGAD and AQP4-IgG–positive NMOSD. The strong positive association with HLA-A*01, -B*08, and -DRB1*03 is suggestive of a role of this haplotype in the etiology of AQP4-IgG–positive NMOSD in patients with European ancestry, whereas in MOGAD no evidence was found for any HLA association in these disorders.

Neuromyelitis optica is an HLA associated disease different from Multiple Sclerosis: a systematic review with meta-analysis

“…In Europe, the association of DRB1 *03 allele group in NMO was found in France 24 (NMO-22.02% vs controls-11.0%, p cS = 0.02) and in the Netherlands 36 (NMO-51.2% vs controls-27.6%, p cS = 0.02).…”

“…After applying the inclusion and exclusion criteria, 13 articles were selected for this review, as shown in Table 1 24 – 36 . The eligible studies analyzed European Caucasians (France 24 , Spain 27 , Denmark 29 and Netherland 36 ), Mexico mestizos 34 , Afro Caribbean 26 , Afro Brazilians (Ribeirão Preto 25 , Rio de Janeiro 33 ), White Brazilians (South Region 35 ) and Asians (South China 28 , South Japan 30 , India 31 and Israel 32 ). There was agreement among the evaluators about the selection of articles.…”

Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population

“…The HLA-DRB1*03:01 allele has been consistently associated with NMO in European populations, and admixed populations with important contribution of the European gene pool (Brazilian mulatto, Afro-Caribbean and a small Mexican mestizo cohort) [13][14][15][16][17][18][19][20] . The frequency of HLA-DRB1*03:01 is as high as 20% in European, North African, Western Asian populations, but ranges from only 0 to 2% in Native Mexican populations 39 .…”

“…HLA alleles previously associated with NMO in populations with European and/or Native American ancestry (HLA-DRB1*03:01 [13][14][15][16][17][18][19][20] , -DRB1*16:02 [21][22][23] and -DQB1*04:02 13,24 ) were in strong LD with the rs9272219 "A" risk allele. In contrast, two alleles significantly associated with decreased NMO risk in the present study (HLA-DRB1*04:07 and -DQB1*03:02) were in strong LD with the rs9272219 "C" allele.…”

“…Like many other autoimmune diseases, NMO is a multifactorial disorder that results from complex interactions between genetic and environmental factors. Recent studies have reported associations of NMO with genetic variation in the Human Leukocyte Antigen (HLA) genome region in chromosome 6, particularly with class II alleles, showing ethnical and geographical differences: The DRB1*03:01 allele has been associated with NMO in European [13][14][15][16] , Brazilian 17,18 , Afro-Caribbean 19 and Mexican patients 20 ; DRB1*16:02 in Southern Han Chinese 21 , Japanese 22 and in Southern Brazilian patients 23 ; DQB1*04:02 in a European-ancestry cohort 13,24 ; and DRB1*04:05 in Southern Brazilians 23 . Moreover, candidate gene studies have reported associations with variation in non-HLA genes such as AQP4 and others involved in immune function (PD-1, IL-17, IL-7R, CD6 and CD58) [24][25][26][27][28] .…”