MONOCLONAL IGM FROM PATIENTS WITH PERIPHERAL DEMYELINATING NEUROPATHIES CROSS-REACT WITH BACTERIAL POLYPEPTIDES

Human monoclonal IgM associated with a demyelinating peripheral neurop athy often feature a distinct antibody activity directed against a glu curonyl sulphate epitope shared by myelin-associated glycoprotein (MAG ), nerve glycolipids and low molecular weight peripheral nerve polypep tides. Earlier studies showed that these IgM use a diverse repertoire of VH and VL genes which exhibit somatic mutations, possibly indicativ e of an antigen-driven process. Here, we investigated whether such mon oclonal IgM may react with environmental bacterial antigens. We found that six patients' sera and purified monoclonal IgM, as well as IgM fr om supernatants of three clonal anti-MAG-secreting cell lines reacted with unique 90-100kD polypeptides from extracts of two out of 10 bacte rial species. Purified MAG was able to inhibit this reactivity. These results indicate molecular mimicry as a possible mechanism of this imm unomediated neuropathy and associated clonal lymphoid disease.