Autoimmune responses to mRNA binding proteins p62 and Koc in diverse malignancies

Two tumor-associated antigens, p62 and Koc, are insulin-like growth factor II (IGF-II) messenger RNA binding proteins. Autoantibodies to p62 have been detected in cancer sera but have not been reported for Koc. This study determined the extent and frequency of autoantibodies to p62 and Koc in diverse malignancies, the epitopes on the antigens, and the presence or absence of cross-reactive antibodies. Recombinant polypeptides were expressed from full-length and partial cDNA constructs and used as antigens in Western blotting, enzyme-linked immunoassay, and immunoprecipitation. After identifying the epitopes, cross-absorption with recombinant polypeptides was used to determine specificity. Sera from 777 patients with 10 different types of malignancy were analyzed. Autoantibodies to p62 were found in 11.6% and to Koc in 12.2% and cumulatively to both antigens in 20.5%, with significant difference from the control populations consisting of normal subjects and autoimmune disease patients (P < 0.01). The immunodominant epitopes were at the amino termini of both antigens and absorption studies showed that the majority of autoantibodies were not cross-reactive. Autoantibodies to p62 and Koc were present in approximately similar frequencies in a variety of malignancies and the immune responses appeared to be independent of each other. The immune responses might be related to overexpression or dysregulation of p62 and Koc in some tumors. (C) 2001 Academic Press.