Lung cancer-related changing profile of B-cell epitopes recognized on mucosal antigens: the Der p1 model.

BACKGROUND

The natural immunoglobulin G (IgG) response towards antigens presented at the mucosal level in patients with lung cancer, the most frequent mucosal malignancy in humans was studied. Compared with healthy control subjects, patients with lung cancer display lower IgG antibody titers toward antigen p1 of the house dust mite, Dermatophagoides pteronyssinus (Der p1), chronically presented to the respiratory mucosa. The present study further characterizes this defect in terms of antibody specificity.

METHODS

Antibody specificity was studied by comparing the IgG binding to native Der p1 (nDer p1) and its products of pepsin hydrolysis (dDer p1) in a solid phase enzyme-linked immunosorbent assay (ELISA) in 148 patients with lung carcinoma, 148 healthy control subjects, and 50 patients with chronic bronchitis. Antibody specificity was also evaluated before and after (5 +/- 1 weeks) surgical excision of the tumor in competition ELISA using streptavidin-biotin technology.

RESULTS

Lung cancer sera had a higher degree of binding to dDer p1 compared with nDer p1, whereas control group sera bound similarly to the two forms of the antigen. Lung cancer sera and control group sera showed distinct capacities to prevent the binding of pooled IgG from each group to nDer p1. The inhibition capacity displayed by cancer sera is changed 5 weeks after cancer removal.

CONCLUSION

These results, somewhat similar to those observed for bovine betalactoglobulin, document the recognition of a different set of epitopes on Der p1 and more generally on mucosal antigens by lung cancer IgG compared with the IgG from control patients. This distinct profile of epitope specificity changes partially soon after cancer removal, suggesting a tumor-dependent disturbance and opens the way to a new class of markers in lung cancer. Furthermore, this study documents a surprising but striking influence of the clinical status on the choice of B-cell immunodominant epitopes in mucosal responses.