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 cells. Every somatic cell is however endowed with a repertoire of membrane-bound 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 complement regulatory molecules expressed in the membrane of human cells (CD46 and CD59) are present in sera from relapsing-remitting MS patients in the acute phase, that they are directed against the active site of the RCA molecules and that they inactivate their regulatory function, thus providing a mechanism by which cells of the nervous system might be damaged in a complement-dependent fashion during the acute MS phase. Moreover, we found that most of these sera also contain antibodies reacting with an epitope of the transmembrane glycoprotein of HIV which is conserved in most retroviruses; this may support the hypothesis that self-reacting antibodies might have arisen in these patients as an immune response after retroviral infection or expression of endogenous retroviral proteins.
Pintér
C
C
Laboratory of Biology and Genetics, Department of Pre-clinical Sciences LITA Vialba, University of Milano, Milano, Italy.
Beltrami
S
S
Caputo
D
D
Ferrante
P
P
Clivio
A
A
D000210:Acute-Phase Reaction / Q000276:immunology; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D018957:CD59 Antigens / Q000276:immunology*; D003169:Complement Inactivator Proteins / Q000276:immunology*; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D006678:HIV / Q000276:immunology; D006801:Humans; D019169:Jurkat Cells; D007962:Leukocytes / Q000166:cytology / Q000276:immunology; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000276:immunology*; D008969:Molecular Sequence Data; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000276:immunology* / Q000821:virology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012190:Retroviridae / Q000276:immunology; D020298:U937 Cells
D015703:Antigens, CD; D000956:Antigens, Viral; D001323:Autoantibodies; C497857:CD46 protein, human; D018957:CD59 Antigens; D003169:Complement Inactivator Proteins; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011994:Recombinant Proteins