Intrinsic lymphocyte defect in Hodgkin's disease: Analysis of the phytohemagglutinin dose-response

Abstract

Cellular immunity was studied in 27 newly diagnosed untreated patients at presentation: delayed hypersensitivity was assessed by the intradermal injection of candida, mumps, streptokinase/streptodornase, and PPD antigens; peripheral blood lymphocytes were cultured in the presence of a range of phytohemagglutinin (PHA) concentrations from 0 to 800 μg/ml, and response measured by tritiated thymidine uptake. Fourteen patients were in stages 1, 2, or 3A; of these, four (36%) were anergic. Of 13 patients in stages 3B or 4, eight (62%) were anergic. Delayed hypersensitivity responses did not distinguish patients in these two staging groups ( P less than 0.1). Peripheral lymphocyte counts were normal in all stage 1-3A patients, and reduced in 10 of 13 (77%) stage 3B-4 patients ( P less than 0.01). PHA responses were reduced in 4 of 14 (29%) patients in stages 1-3A, and in 12 of 13 (92%) patients in stages 3B-4 ( P less than 0.005); serum factors did not account for observed abnormalities in PHA response. All of the ten lymphopenic patients showed a reduced lymphocyte response to PHA, and in seven the response was reduced at all PHA concentrations employed. However, in seven patients, including four with normal lymphocyte counts, the lymphocyte response was reduced only at low PHA concentrations and was normal at high concentrations. This study shows the lymphocyte dose-response to PHA to be a sensitive index of a lymphocyte defect in Hodgkin's disease and is a useful adjunct in clinical staging. The results indicate that a functional lymphocyte defect is a frequent finding in untreated patients and appears to precede the development of lymphopenia.