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

• Published in: Acta neurologica Scandinavica Vol. 138; no. 3; pp. 219 - 226
• Main Authors: Hong, Y., Li, H.‐F., Romi, F., Skeie, G. O., Gilhus, N. E.
• Format: Journal Article
• Language: English
• Published: Denmark John Wiley & Sons, Inc 01.09.2018
• Subjects: Alleles; Drb1 protein; Female; Gene Frequency; genetic polymorphism; Genetic Predisposition to Disease - genetics; Genotype; Genotypes; Haplotypes; Histocompatibility antigen HLA; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; human leucocyte antigen; Humans; Kinases; Meta-analysis; muscle‐specific tyrosine kinase; Myasthenia; Myasthenia gravis; Myasthenia Gravis - genetics; Myasthenia Gravis - immunology; Neuromuscular junctions; Patients; Protein-tyrosine kinase; Receptor Protein-Tyrosine Kinases - immunology; Receptors, Cholinergic - immunology; meta-analysis; myasthenia gravis; muscle-specific tyrosine kinase; human leucocyte antigen; genetic polymorphism
• ISSN: 0001-6314; 1600-0404; 1600-0404
• DOI: 10.1111/ane.12951

Objectives Myasthenia gravis (MG) represents a spectrum of clinical subtypes with differences in disease mechanisms and treatment response. MG with muscle‐specific tyrosine kinase (MuSK) antibodies accounts for 1%‐10% of all MG patients. We conducted a meta‐analysis to evaluate the association between HLA genes and MuSK‐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 MuSK‐MG patients and healthy controls were extracted from each included study. Results The meta‐analysis showed that HLA DQB1*05, DRB1*14 and DRB1*16 were strongly associated with an increased risk of MuSK‐MG (P < .0001), whereas HLA DQB*03 was less frequent in MuSK patients compared with healthy controls (P < .05). Haplotype analysis showed that these DQB1 and DRB1 alleles were closely linked, forming both risk (DQ5‐DR14, DQ5‐DR16, P < .0001) and protective (DQ3‐DR4, DQ3‐DR11, P < .05) haplotypes. Conclusion The distinct genetic patterns of MuSK‐MG indicate that variation in HLA class II genes plays an important role in the pathogenesis of MuSK‐MG patients.