Alpha-2-macroglobulin deficiency in patients with advanced prostate cancer

Four out of approximately 36,000 specimens, examined by immunoelectrophoresis, showed no precipitin line of alpha-2-macroglobulin (alpha 2M) with anti-whole human serum and antiserum to alpha 2M. Serum alpha 2M levels were below 10 mg/100 ml with single radial immunodiffusion. These cases were diagnosed as having prostate cancer based on prostate biopsy. After estrogen or anti-androgen therapy, the initially severe deficiency of alpha 2M changed toward normal limits. Phytohemagglutinin (PHA)-induced lymphocytes from patients with severe alpha 2M deficiency revealed normal response. Sera from patients with alpha 2M deficiency and healthy subjects (serum alpha 2M concentration of 8-208 mg/100 ml) did not suppress lymphocyte response to PHA, while purified alpha 2M from fetal cord and healthy sera, and serum from a patient with advanced urinary cancer (serum alpha 2M concentration above 360 mg/100 ml) to PHA-induced lymphocytes demonstrated a dose-dependent suppression. Thus, these results indicate that alpha 2M in elevated concentration results in decreased PHA-induced lymphocyte response and suggest that alpha 2M may have, principally suppressive, immunoregulatory properties in vivo.