title: High frequency of DQB1*05 and absolute absence of DRB1*13 in muscle-specific tyrosine kinase positive myasthenia gravis.
abstract: OBJECTIVE
  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.
authors: Neurology Clinic, Department for Neuromuscular Disorders, Clinical Center of Serbia, Belgrade, Serbia; Medical Faculty, University of Belgrade, Belgrade, Serbia.
authors: A V
authors: AV
authors: Nikolic
authors: Z P
authors: ZP
authors: Andric
authors: R B
authors: RB
authors: Simonovic
authors: V M
authors: VM
authors: Rakocevic Stojanovic
authors: I Z
authors: IZ
authors: Basta
authors: S D
authors: SD
authors: Bojic
authors: D V
authors: DV
authors: Lavrnic
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000235:genetics* / Q000276:immunology; D020794:Receptor Protein-Tyrosine Kinases / Q000276:immunology*; D011950:Receptors, Cholinergic / Q000276:immunology*; D055771:Serbia; D055815:Young Adult
chemical_list: D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I; D011950:Receptors, Cholinergic; C095714:MUSK protein, human; D020794:Receptor Protein-Tyrosine Kinases
keywords: human leukocyte antigens; muscle-specific tyrosine kinase; myasthenia gravis