Clinical and serological associations of autoantibodies to GW bodies and a novel cytoplasmic autoantigen GW182

A novel autoantigen named GW182 was recently identified when the serum from a patient with a sensory ataxic polyneuropathy was used to immunoscreen a HeLa cDNA library. Unique features of the GW182 protein include 39 repeats of glycine (G) and tryptophan (W) residues, binding to a subset of messenger RNA and localization to unique structures within the cytoplasm that were designated GW bodies (GWBs). The goal of the present study was to identify the clinical features of patients with anti-GW182 antibodies and to characterize the B cell anti-GW182 response by defining the epitopes bound by human autoantibodies. The most common clinical diagnosis of patients with anti-GW182 antibodies was Sjogren's syndrome followed by mixed motor/sensory neuropathy, and systemic lupus erythematosus. Of interest, 5 (28%), 9 (50%), and 3 (17%) of the 18 sera that react with GWBs had autoantibodies to the GW182 and the 52 kDa and 60 kDa SS-A/Ro autoantigens, respectively. Epitopes bound by the human autoantibodies were mapped to the GW-rich middle part of the protein, the non-GW rich region, and the C-terminus of GW182 protein. None of the GW182 epitopes had significant sequence similarities to other known proteins. GW182 represents a new category of ribonucleoprotein autoantigens.