DIFFERENCES IN SEROLOGICAL IGA RESPONSES TO RECOMBINANT BACULOVIRUS-DERIVED HUMAN PAPILLOMAVIRUS E2 PROTEIN IN THE NATURAL-HISTORY OF CERVICAL NEOPLASIA

Infection with certain types of human papillomavirus (HPV) presents a high risk for me subsequent development ai cervical intraepithelial ne oplasia (GIN) and cervical carcinoma. Immunological mechanisms are lik ely to play a role in control of cervical HPV lesions. The HPV E2 prot ein has roles in virus replication and transcription, and loss of E2 f unctions may be associated with progression of cervical neoplasia. Acc ordingly, it is of interest to monitor immune responses to the E2 prot ein, and previous studies have reported associations between serologic al reactivity to E2 peptide antigens and cervical neoplasia. In order to investigate serological responses to native, full-length E2 protein , we expressed HPV-16 E2 proteins with and without an N-terminal polyh istidine tag using the baculovirus system. Purified HPV-16 E2 protein was used to develop enzyme-linked immunosorbent assays to detect serol ogical IgG and IgA responses in cervical neoplasia patients and contro ls. We found that serum IgA levels against the E2 protein were elevate d in CIN patients relative to normal control subjects but were not ele vated in cervical cancer patients. Moreover, there appeared to be a gr adient of response within cervical neoplasia such that the highest ant ibody levels were seen in lower grades of neoplasia up to CIN a, where as lower levels were observed in CIN 3 and still lower levels in cervi cal carcinoma. These findings suggest that the IgA antibody response t o E2 may associate with stage and progression in cervical neoplasia.