Serologic responses in patients with malignant mesothelioma - Evidence forboth public and private specificities

Malignant mesothelioma (MM) is a pulmonary malignancy that appears to be im munogenic based on a large number of studies in both animals and humans. Th is notion is supported by our recent demonstration using Western blot analy sis of immunoglobulin G antibodies reactive with a variety of autoantigens in many patients with MM. In view of the enormous potential of such antigen s in early diagnosis, immunotherapy, and vaccination of at-risk individuals , it was essential to identify these antigens. We therefore applied the SER EX technique (serologic identification by recombinant expression cloning), using a serum pool from six patients as the probe against an expressed comp lementary DNA library derived from a cloned MM cell line. We screened over one million recombinants and obtained sequence information on eight antigen s that had provoked immunoglobulin heavy chain class switching, presumably as a consequence of T-cell recognition. Six of these antigens were identifi able (U2AF[65], Siah binding protein, topoisomerase II beta, ZFM1, mIre1, a nd pendulin), and of the others, one was found as a single EST from a myotu be library (Jemm-1); the other (Jemm-2) was not represented in any EST data base even as a weak homolog. Consistent with our previous findings, each of the characterizable antigens would be expected to be associated with the c ell nucleus. Each of the autoantibody specificities was uniquely associated with a single patient with the exception of antibodies to TOPII beta and U 2AF(65). We found 13 of 14 (93%) patients with MM had antibodies to TOPII b eta and two of 14 (14%) patients had antibodies to U2AF(65). The number of serum reactivities, taken as a measure of the complexity of the immune resp onse, correlates with patient survival and with an index of systemic inflam mation. These data suggest that a broader range of serologic reactivities r eflects a more active host response to the presence of tumor.