Impaired cell-mediated immunity in hemophilia. II. Persistence of subclinical immunodeficiency and enhancement of natural killer activity by lymphokines
Lederman, M.M.; Ratnoff, O.D.; Schacter, B.; Shoger, T.
Journal of Laboratory and Clinical Medicine 106(2): 197-204
1985
ISSN/ISBN: 0022-2143 PMID: 2410523 Document Number: 251386
Follow-up studies were performed in 11 patients with asymptomatic classic hemophilia, who on initial study 8-12 mo. previously had demonstrated abnormalities of lymphocyte phenotype and function. Although all subjects remained well, diminished lymphocyte proliferative responses, natural killer activity and decreased ratios of OKT4 helper/OKT8 suppressor lymphocytes persisted. The absolute number of OKT4 helper lymphocytes fell in the patients from a mean of 745 .+-. 73/.mu.l in the 1st study to 585 .+-. 50/.mu.l in the follow-up study, which was lower than the control value of 857 .+-. 87 (P < 0.02). Despite diminished natural killer activity, patients with hemophilia had at least normal numbers of natural killer cells as determined by the presence of the OKM1 antigens and Giemsa staining to identify large granular lymphocytes. Patients with hemophilia had more Leu 11a-positive cells than controls. Lymphocyte binding to tumor targets was not diminished. Removal of adherent cells did not increase patients' natural killer activity to control levels. Incubation of patients' lymphocytes with .alpha.-interferon, .gamma.-interferon or interleukin-2 resulted in enhancement of natural killer activity but did not reach control levels. The diminished natural killer activity in patients with hemophilia retained responsiveness to lymphokines and was caused either by an intrinsic or acquired defect in the natural killer cell or by modulation by a nonadherent cell. Subclinical immunodeficiency in patients with hemophilia is not transient and is associated with a diminished number of OKT4 helper cells, a finding often associated with clinical immunodeficiency.