The cytoplasmic linker protein CLIP-170 is a human autoantigen

The purpose of this study was to identify autoantigens that are recognized by human sera and are associated with a speckled cytoplasmic fluorescent staining pattern on tissue culture cells, and to determine clinical features associated with specific autoantibodies. A serum from a patient with systemic lupus erythematosus was used to identify a 3.7-kb cDNA insert from a HeLa cell expression library. The purified cDNA (VLK2.1) encoded a peptide of 1051 amino acids that shared 98.4% similarity with the carboxyl terminal portion of a previously reported 170 kD protein named cytoplasmic linker protein-170 (CLIP-170). Antibodies affinity purified with the recombinant CLIP-170 protein, the prototype human serum and a monoclonal antibody raised against CLIP-170 exhibited identical speckled staining of the cytoplasm in HEp-2 cells. The human autoantibodies reacted with the purified recombinant protein in a Western immunoblot and immunoprecipitated the in vitro translated recombinant protein. Three additional human sera also immunoprecipitated the recombinant CLIP-170 protein. The clinical diagnoses in these patients were limited scleroderma, glioblastoma and idiopathic pleural effusion. This is the first report that identifies CLIP-170 as a human autoantigen.