Increased frequency of HLA class II alleles DRB1*0301 and DQB1*0201 in Lambert-Eaton myasthenic syndrome without associated cancer.
Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular disorder characterized by pathogenic autoantibodies directed against the presynaptic voltage-gated calcium channels (VGCC), resulting in a clinical syndrome of proximal muscular weakness and autonomic dysfunction. Sixty percent of LEMS cases are associated with cancer, most commonly small cell carcinoma of the lung. In the 40% of LEMS patients without carcinoma, the stimulus for the production of VGCC autoantibodies is unknown; however, these LEMS patients have multiple other organ-specific autoantibodies. To investigate the autoimmune basis of noncancer associated LEMS (NCA-LEMS), high resolution typing of major histocompatibility loci was performed in 23 patients with NCA-LEMS. NCA-LEMS was strongly associated with DRB1*0301 (p<0.0001) and DQB1*0201 (p<0.0001), suggesting that NCA-LEMS is an autoimmune disorder associated with the DR3-DQ2 extended haplotype.
Parsons
K T
KT
Virginia Mason Research Center, Seattle, Washington, USA. kparsons@vmresearch.org
Kwok
W W
WW
Gaur
L K
LK
Nepom
G T
GT
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D006684:HLA-DR Antigens / Q000145:classification / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D015624:Lambert-Eaton Myasthenic Syndrome / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen