The ribosomal P0 protein induces a spontaneous immune response in patients with head and neck advanced stage carcinoma that is not dependent on its overexpression in carcinomas

Abstract

A typical feature in systemic lupus erythemathosus patients is the presence of autoantibodies to the carboxylterminal homologous P proteins (P0, P1, P2) domain (C-22 P0 epitope). In this report we provide evidence for the in vivo immunogenicity of the P0 protein in head and neck cancer patients as well as overexpression by immunohistochemistry of the C-22 P0 epitope in invasive carcinomas (55/57). Overexpression of this epitope was also significantly associated with a number of pathological lesions arising in the head and neck stratified epithelium including acanthosis (8/8), benign tumors (11/11), dysplasia (23/25) and in situ carcinomas (9/9). Intermediate cell layer restricted epitope overexpression was observed in well differentiated carcinomas, while undifferentiated tumors showed overexpression throughout the cell layers. Employing recombinant P proteins, sera from 40 of the 57 carcinoma patients and 39 normal donors, were subjected to immunoblot analysis. Immunity to P0 protein (7/40) was associated with malignancy and with advanced disease stage, but it was not dependent on the C-22 P0 epitope overexpression, although it was the preferential autoantibody target in 4 patients. Increased expression of the C-22 P0 epitope on the surface of pharynx cancer cells following cellular stress in vitro, may imply P0 protein presentation as an in vivo autoantibody target in cancer patients. Evidence for immunity to the P0 protein, as well as overexpression in patients with head and neck carcinoma may be relevant for monitoring cancer progression, in planning immunotherapeutic strategies, and contribute to the understanding of immuno-biological behaviour of head and neck carcinomas.

Salivary Auto-Antibodies as Noninvasive Diagnostic Markers of Oral Cavity Squamous Cell Carcinoma

“…Despite a high specificity of using serum auto-Abs for distinguishing OSCC from the healthy group, using most of them for OSCC detection are not sensitive enough. For instance, the sensitivities of using serum anti-p53, antiHsp60, and anti-RPLP0 for OSCC detection are 18.7%, 10.3%, and 10.3%, respectively (25,27,28,32). In contrast, Table 2.…”

“…Herein, we established a multiplexed immunobead-based platform to simultaneously detect five salivary auto-Abs, including anti-p53, anti-survivin, anti-CK8, anti-Hsp60, and anti-RPLP0, and verified their effectiveness as OSCC biomarkers for the first time. Although these auto-Abs have been individually reported as serum biomarkers in patients with head and neck cancers (25)(26)(27)(28)(29)(30)(31)(32), their salivary levels in patients with OSCC as well as their diagnostic and prognostic values have not been investigated on a large scale until now. Importantly, our case cohorts include two groups of noncancerous patients, who are with LR-and HR-OPMD, respectively (Table 1), for additionally evaluating if such chronic inflammatory diseases in the oral cavity may lead to dysregulated levels of salivary autoAbs.…”

“…Although the serum anti-p53, anti-survivin, anti-CK8, anti-Hsp60, and anti-RPLP0 have been reported as biomarker candidates of OSCC (25)(26)(27)(28)(29)(30)(31)(32), the investigation on their salivary levels in patients with OSCC is relatively limited. To simultaneously measure the salivary levels of these auto-Abs, we established a platform combining a direct ELISA with a bead-based suspension array system.…”

“…25), and anti-60S acidic ribosomal protein P0 (RPLP0; ref. 32). Although each by itself has a limited specificity and/or sensitivity for OSCC detection, it is uncertain whether a combined panel of these auto-Abs would be more efficacious than an individual auto-Ab is.…”

Evidence of a humoral response to a novel protein WARF4 embedded in the West Nile virus NS4B gene encoded by an alternative open reading frame

“…The 1:1000 dilution was chosen for testing as the highest serum concentration that lacked substantial background reactivity. After washing, the filters were incubated with anti-horse IgG whole-molecule peroxidase conjugate (Sigma) and developed by a chemiluminescent kit (Sigma) as previously described (18)(19)(20). Criteria of positivity was the appearance of an immunoreactive band in the WARF4 sample, co-migrating with the one visualized by the anti-his antibody and not in the bacterial cell extract used as negative control.…”