A POSSIBLE ROLE OF NO IN THE ELICITATION OF NEW EPITOPES IN AUTOIMMUNITY

It has been proposed (1) that NO may complex to amino acid residues in autoantigens thus coniditioning an autoimmune response. This idea stems from the observation that circulating antibodies against a conjugated S-nitrosocysteine epitope are present in sera of multiple sclerosis (MS) patients. The expression of the inducible form of nitric oxide synthase (iNOS) in differentiated and activated monocytes freshly obtained from patients with MS and with Graves disease (GD) has been demonstrated (2,3). We report now that iNOS is also present in monocytes from patients with type I diabetes mellitus (IDDM). We nytrosylated autoantigens, such as myelin basic protein, thyrogobulin and proinsulin and analyzed the degradation pattern of these proteins when exposed to different proteases, including those of PBMC from patients with autoimmune diseases. Nitrosylated proteins exhibited a proteolytic pattern different from that of native protein. Depending on the state of differentiation of monocytes from patients with MS, GD or IDDM, different patterns of proteolytic activity could be observed. PBMC from patients with these diseases produced cytokines belonging to activated monocytes and Th1 cells. It is known that these cytokines are capable of inducing iNOS in thyrocytes, astrocytes and pancreatic β-cells. These observations, together with data now reported, suggest that NO may be playing a role in the elicitation of new epitopes mediated by changes in autoantigen processing. 1. Boullerne, AI et al. (1995) J. Neuroimmunol. 60, 117-124.- 2. Lopez-Moratalla, N et al. (1996) Biochem. Biophys. Res. Commun. 226,723-729.- 3. Lopez-Moratalla, N et al. (1997) Nitric Oxide： Biology and Chemistry 1, 95-104. Grant SAF97-0233 from CICYT, Spain.