THE INVOLVEMENT OF CD14 IN STIMULATION OF TNF PRODUCTION FROM PERIPHERAL MONONUCLEAR-CELLS ISOLATED FROM PNH PATIENTS

Peripheral blood mononuclear cells (PBMC) from six patients with parox ysmal nocturnal haemoglobinuria (PNH) were analysed by flow cytometry for expression of CD14 and for ability to respond to bacterial lipopol ysaccharide and beta 1-4 linked polymannuronic acid by TNF secretion. Expression of cell surface CD14 could not be detected on cells from th e PNH patients, whereas the levels of expression of other monocyte ant igens, e.g. CD33 and CD13, were comparable to that of cells from healt hy subjects. The cells from the patients with PNH responded with secre tion of significantly less TNF after stimulation with LPS and polymann uronic acid than mononuclear cells from healthy subjects, suggesting a n impaired ability in PNH to respond to bacterial infection by TNF sec retion from monocytes. Soluble CD14 appeared to be involved in the res idual activation of CD14 negative PBMC, and the sera of these patients contained normal or slightly elevated levels of soluble CD14. After a llogeneic bone marrow transplantation in one patient the monocytes exp ressed CD14 at normal levels and responded normally with respect to th eir ability to generate TNF upon stimulation.