High Frequency of DQB1*05 and Absolute Absence of DRB1*13 in Muscle-Specific Tyrosine Kinase Positive Myasthenia Gravis

Eur J Neurol. 2015 Jan;22(1):59-63. doi: 10.1111/ene.12525. Epub 2014 Jul 29.

Abstract

Background and purpose: Myasthenia gravis (MG) is an autoimmune disease but certain genetic factors predispose its development. Since susceptibility to different forms of MG is linked to a number of allelic variants, the aim of this study was to explore the human leukocyte antigen (HLA) profile of our patients with muscle-specific tyrosine kinase (MuSK) MG.

Methods: Human leukocyte antigen (HLA) typing was performed in our cohort of 31 MuSK MG patients available for the study. The allele groups of DRB1* and DQB1* loci were typed with sequence-specific oligonucleotide probes and high resolution typing for DQB1* was performed using sequence-specific primers. HLA frequencies were compared with unrelated healthy bone marrow donors.

Results: Significant association of MuSK MG with alleles DRB1*14 [odds ratio (OR) 3.8], DRB1*16 (OR 3.3) (P < 0.01) and DQB1*05 (OR 2.2) (P < 0.05) was found. In our patients the most frequent DQB1* allele was DQB1*05:02. An absolute absence of DRB1*13 in our cohort of MuSK MG patients was also found, whilst this allele was present in 25% (495/1992) of control subjects (OR 0) (P < 0.01). The HLA DRB1*16-DQB1*05 (OR 2.9) haplotype was found to be associated with MuSK MG (P < 0.05).

Conclusions: The strong association of MuSK MG with DQB1*05 alleles observed in patient series from other countries was confirmed. The novel finding in our cohort of MuSK MG patients was the absolute absence of DRB1*13 allele, which might have a protective role in the development of MuSK MG, at least in our population.

Keywords: human leukocyte antigens; muscle-specific tyrosine kinase; myasthenia gravis.

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Gene Frequency
  • HLA-DQ beta-Chains / genetics*
  • HLA-DRB1 Chains / genetics*
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • Male
  • Middle Aged
  • Myasthenia Gravis / genetics*
  • Myasthenia Gravis / immunology
  • Receptor Protein-Tyrosine Kinases / immunology*
  • Receptors, Cholinergic / immunology*
  • Serbia
  • Young Adult

Substances

  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • HLA-DRB1 Chains
  • Histocompatibility Antigens Class I
  • Receptors, Cholinergic
  • MUSK protein, human
  • Receptor Protein-Tyrosine Kinases