INDUCIBLE NITRIC-OXIDE SYNTHASE IN MONOCYTES FROM PATIENTS WITH GRAVES-DISEASE

The presence of inducible nitric oxide synthase (iNOS) in fresh monocy tes from patients with Graves' disease was demonstrated for the first time. Immunophenotypic analysis showed a profile reflecting a state of activation and differentiation of monocytes. Incubation of lymphomono nuclear cells from healthy volunteers in the presence of synthetic pep tides with sequences related to thyroid autoantigens (TSH receptor, th yroid peroxidase, or thyroglobulin) led to a stimulation of monocytes manifested by a change in phenotype and expression of iNOS. This expre ssion did not take place on isolated monocytes, unless products associ ated with Th1 activity were present in the medium. Active peptides con tained a characteristic ''2-6-11'' motif already described [Lopez-Mora talla et al. (1995) Biochim. Biophys. Acta 1265, 181-188]. These resul ts are suggestive of a new role for autoantigens in the pathogenesis o f Graves' disease: that of inducing the expression of iNOS and activat ing the monocyte possibly underlying the autoimmune response. (C) 1996 Academic Press, Inc.