HLA and Mu SK ‐positive myasthenia gravis: A systemic review and meta‐analysis

Objectives Myasthenia gravis ( MG ) represents a spectrum of clinical subtypes with differences in disease mechanisms and treatment response. MG with muscle‐specific tyrosine kinase (Mu SK ) antibodies accounts for 1%‐10% of all MG patients. We conducted a meta‐analysis to evaluate the association between HLA genes and Mu SK ‐ MG susceptibility. Subjects and methods Studies were searched in Pubmed, EMBASE database and other sources between 2001 and 2018. Genotype, allele and haplotype frequencies of HLA loci in Mu SK ‐ MG patients and healthy controls were extracted from each included study. Results The meta‐analysis showed that HLA DQB 1*05, DRB 1*14 and DRB 1*16 were strongly associated with an increased risk of Mu SK ‐ MG ( P  <   .0001), whereas HLA DQB *03 was less frequent in Mu SK patients compared with healthy controls ( P  <   .05). Haplotype analysis showed that these DQB 1 and DRB 1 alleles were closely linked, forming both risk ( DQ 5‐ DR 14, DQ 5‐ DR 16, P  < .0001) and protective ( DQ 3‐ DR 4, DQ 3‐ DR 11, P  < .05) haplotypes. Conclusion The distinct genetic patterns of Mu SK ‐ MG indicate that variation in HLA class II genes plays an important role in the pathogenesis of Mu SK ‐ MG patients.