Increased frequency of HLA class II alleles DRB1∗0301 and DQB1∗0201 in Lambert-Eaton myasthenic syndrome without associated cancer

Abstract

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.