Human sera possess complement-dependent cytotoxic reactivity against autologous and allogeneic cultured normal skin fibroblasts. Previous studies indicated that the natural antibody reactivity is directed against fetal antigens expressed on these cells in tissue culture. The reactivity was further characterized in the present study. Chromatographic analysis of a normal serum indicated that its reactivity belonged to the immunoglobulin M (19S) class of immunoglobulins. Sera from 22 preoperative tumor-bearing osteogenic sarcoma patients, 30 tumor-bearing soft-tissue sarcoma patients, and 52 age- and sexmatched normal individuals were tested against allogeneic skin fibroblasts. The patient and normal groups displayed wide, overlapping ranges of cytotoxicity. The osteogenic sarcoma group showed a small but significant increase in mean cytotoxicity compared to the controls, whereas the soft-tissue sarcoma sera were not significantly different from the controls. Reactivities in the sera of patients whose tumors recurred were not significantly different from those of the patients who remained disease free. Cytotoxic levels in sera from eight osteogenic sarcoma patients followed throughout the clinical course remained constant up to the time of documented recurrence and were not affected by surgical removal of the primary tumor or Bacillus Calmette-Guérin immunotherapy. In three of four patients whose tumors recurred, cytotoxic levels fell, but only after documented recurrence. The natural antibody reactivity against normal fibroblasts does not appear useful as a marker for diagnosis, prognosis, or monitoring tumor presence in sarcoma patients.

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