Presence of autoantibodies against complement regulatory proteins in relapsing-remitting multiple sclerosis

Complement was proposed to play an important role in the onset of Multiple Sclerosis (MS) lesions by inducing physical damage to myelin-producing cell s. Every somatic cell is however endowed with a repertoire of membrane-boun d molecules which normally down-regulate the complement activation cascade (Regulators of Complement Activation, RCA) and therefore protect cells from complement-dependent lysis. We show here that antibodies against two compl ement regulatory molecules expressed in the membrane of human cells (CD46 a nd CD59) are present in sera from relapsing-remitting MS patients in the ac ute phase, that they are directed against the active site of the RCA molecu les and that they inactivate their regulatory function, thus providing a me chanism by which cells of the nervous system might be damaged in a compleme nt-dependent fashion during the acute MS phase. Moreover, we found that mos t of these sera also contain antibodies reacting with an epitope of the tra nsmembrane glycoprotein of HIV which is conserved in most retroviruses; thi s may support the hypothesis that self-reacting antibodies might have arise n in these patients as an immune response after retroviral infection or exp ression of endogenous retroviral proteins.