title: Differences in serological IgA responses to recombinant baculovirus-derived human papillomavirus E2 protein in the natural history of cervical neoplasia.
abstract: Infection with certain types of human papillomavirus (HPV) presents a high risk for the subsequent development of cervical intraepithelial neoplasia (CIN) and cervical carcinoma. Immunological mechanisms are likely to play a role in control of cervical HPV lesions. The HPV E2 protein has roles in virus replication and transcription, and loss of E2 functions may be associated with progression of cervical neoplasia. Accordingly, it is of interest to monitor immune responses to the E2 protein, and previous studies have reported associations between serological 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 polyhistidine tag using the baculovirus system. Purified HPV-16 E2 protein was used to develop enzyme-linked immunosorbent assays to detect serological IgG and IgA responses in cervical neoplasia patients and controls. We found that serum IgA levels against the E2 protein were elevated in CIN patients relative to normal control subjects but were not elevated in cervical cancer patients. Moreover, there appeared to be a gradient of response within cervical neoplasia such that the highest antibody levels were seen in lower grades of neoplasia up to CIN 2, whereas lower levels were observed in CIN 3 and still lower levels in cervical carcinoma. These findings suggest that the IgA antibody response to E2 may associate with stage and progression in cervical neoplasia.
authors.affiliation: Department of Molecular Biology, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
authors.forename: L
authors.initials: L
authors.lastname: Rocha-Zavaleta
authors.forename: D
authors.initials: D
authors.lastname: Jordan
authors.forename: S
authors.initials: S
authors.lastname: Pepper
authors.forename: G
authors.initials: G
authors.lastname: Corbitt
authors.forename: F
authors.initials: F
authors.lastname: Clarke
authors.forename: N J
authors.initials: NJ
authors.lastname: Maitland
authors.forename: C M
authors.initials: CM
authors.lastname: Sanders
authors.forename: J R
authors.initials: JR
authors.lastname: Arrand
authors.forename: P L
authors.initials: PL
authors.lastname: Stern
authors.forename: S N
authors.initials: SN
authors.lastname: Stacey
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000032:analysis*; D016367:Baculoviridae / Q000235:genetics; D002277:Carcinoma / Q000276:immunology / Q000821:virology*; D002846:Chromatography, Affinity; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis*; D007074:Immunoglobulin G / Q000032:analysis; D008875:Middle Aged; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D027383:Papillomaviridae / Q000276:immunology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000276:immunology / Q000302:isolation & purification; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000821:virology*
chemical_list: D000914:Antibodies, Viral; D017931:DNA Primers; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009856:Oncogene Proteins, Viral; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases