Target antigen in chronic inflammatory demyelinating polyradiculoneuropathy

The primary purposes of this study were to investigate humoral factors in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), to determine pathogenicity of the factors found, and to detect possible target antigens in CIDP. Sera from 22 CIDP patients of whom 12 responded to plasma exchange therapy and 10 needed other therapy, were tested by means of enzyme-linked immunosorbent assay, immunofluorescence and Western blot techniques. Anti-whole myelin, anti-myelin glycoproteins (e.g. P0, P2, PMP22 and myelin associated glycoprotein), anti-myelin glycolipids (e.g. GMl, GM2, Gle, GDla, Gle, Gal-C and Gal-S) antibodies and complement reactivity were detected. Using systemic administration after opening the blood-nerve barrier (BNB) and intraneural injection, Lewis rats were assessed electrophysiologically, morphologically and clinically before and after administrated CIDP serum. Methods of antibody purification and protein sequencing were also applied. The results revealed that one or more antibodies to whole peripheral nerve myelin, myelin glycolipids (GMl, Gle, Qle, GM2 and Gal-S) and myelin glycoproteins (P0) and complement (C3) reactivity were found in 16 (73%) of 22 CIDP sera. Six had anti—P0 IgG antibody, four of which had antimyelin IgG antibody and C3 reactivity. Five had anti-myelin IgM antibody, of which four were directed against gangliosides and two showed C3 reactivity. Five had anti-ganglioside antibody, of which two showed C3 reactivity. One had C3 reactivity alone. Five had neither anti-PO, anti-myelin or anti— ganglioside antibody, nor C3 reactivity. No sera had detectable antibodies to myelin associated glycoprotein, PMP22, P2, GDla or Gal-C. Pathogenicity to peripheral nerve was demonstrated in four of six sera which contained IgG anti-P0 antibody and C3 reactivity. Conduction block and demyelination were induced by intraneural injection of these four sera and their IgG, and by systemic transfer when the BNB had been opened by activated T cells. The specificity of the antigen-antibody reaction was displayed by the binding of F(ab)2 to the P0 protein. Loss of pathogenicity was showed following absorption by P0 but not by P2. Protein sequencing showed that the target antigen is a 30kDa peripheral nervous system myelin protein, the P0 protein