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

Abstract

Neuromyelitis Optica and Multiple Sclerosis are idiopathic inflammatory demyelinating diseases of the central nervous system that currently are considered distinct autoimmune diseases, so differences in genetic susceptibility would be expected. This study aimed to investigate the HLA association with Neuromyelitis Optica by a systematic review with meta-analysis. The STROBE instrument guided research paper assessments. Thirteen papers published between 2009 and 2020 were eligible. 568 Neuromyelitis Optica patients, 41.4% Asians, 32.4% Latin Americans and 26.2% Europeans were analyzed. Only alleles of the DRB1 locus were genotyped in all studies. Neuromyelitis Optica patients have 2.46 more chances of having the DRB1*03 allelic group than controls. Ethnicity can influence genetic susceptibility. The main HLA association with Neuromyelitis Optica was the DRB1*03:01 allele in Western populations and with the DPB1*05:01 allele in Asia. Differences in the Multiple Sclerosis and Neuromyelitis Optica genetic susceptibility was confirmed in Afro descendants. The DRB1*03 allelic group associated with Neuromyelitis Optica has also been described in other systemic autoimmune diseases.

Figure 1

Study identification flowchart. Study identification flowchart following the PRISMA statement. MEDLINE Medical Literature Analysis and Retrieval System Online, LILACS Scientific and Technical Literature of Latin America and the Caribbean, SciELO Scientific Electronic Library Online.

Figure 2

Meta-analysis: association of DRB1*03 allelic group with NMO. Comparison of DRB1*03 allele group association using meta-analysis based on the OR and the confidence interval (95% CI) described in the thirteen studies. The forest plot shows the summary measure of OR equal to 2.46 (95% CI 2.01–3.01). That is, patients with neuromyelitis optica are 2.46 times more likely to have the DRB1*03 allele group than controls. In the West, studies are not heterogeneous (I² = 0.00%; p = 0.92), with the measure of OR equal to 2.38 (95% CI 1.90–2.97), but in Asia the result of the meta-analysis showed a heterogeneity of 67% (I² = 66.91%; p = 0.02).

Figure 3

Distribution of the HLA DRB1 alleles associated to NMO and MS in NMO and MS groups. (a) Comparison of the frequency of DRB1*15 allele group in the NMO and MS groups. (b) Comparison of the frequency of DRB1*03 allele group in the NMO and MS groups. Caucasians do not differ in terms of the DRB1 allelic profile. Brazilian populations with strong African ancestry (Ribeirão Preto (RP) and Rio de Janeiro (RJ) had different distribution of DRB1 alleles in NMO and MS groups. The significance (p) of each comparison is shown in the figure. NS not significant.