Defects in monocyte polarization and dendritic cell clustering in patients with Graves' disease. A putative role for a non-specific immunoregulatory factor related to retroviral p15E.

A depressed chemotactic responsiveness of monocytes and a depressed cluster capability of dendritic cells have been found in diseases such as chronic purulent infections of the respiratory tract and in various types of malignancies. These impairments in monocyte and dendritic cell function could be ascribed to the action of a low molecular weight factor (LMWF; less than 25 kDa) circulating in the serum of the patients. The factor, which seems to be a non-specific immunoregulatory factor, shares a structural homology with p15E, the capsular protein of murine and feline leukaemogenic retroviruses. In order to study the chemotactic responsiveness of monocytes and the cluster capability of dendritic cells of Graves' patients, monocytes were isolated from the peripheral blood and dendritic cells were prepared from these peripheral blood monocytes by exposure to metrizamide. Monocytes were studied for their chemotactic responsiveness measuring their capability to polarize (morphological changes determined by light microscopy) after stimulation with the chemoattractant fMLP. Dendritic cells were studied for their capability to form clusters with allogeneic lymphocytes. A defective fMLP-induced monocyte polarization was found (16 vs 37% in healthy controls), whereas the dendritic cells showed a defective clustering (60 clusters vs 151 clusters in healthy controls). The effect of fractions of less than 25 kDa prepared from the serum of Graves' patients on healthy donor monocytes and dendritic cells was studied to test the presence of p15E-like factors. The serum fractions had a significant inhibitory effect on monocyte polarization and dendritic cell clustering.(ABSTRACT TRUNCATED AT 250 WORDS)