HUMAN-IGM PARAPROTEINS DEMONSTRATE SHARED REACTIVITY BETWEEN CAMPYLOBACTER-JEJUNI LIPOPOLYSACCHARIDES AND HUMAN PERIPHERAL-NERVE DISIALYLATED GANGLIOSIDES

IgM paraproteins from patients with CANOMAD (chronic ataxic neuropathy , ophthalmoplegia, M-protein, agglutination, anti-disialosyl antibodie s) react with NeuAc(alpha 2-8)NeuAc epitopes on a wide range of gangli osides including GQ1b, GT1a, GD1b and GD3. The tissue distribution of reactive antigens in human peripheral nerve has not been addressed in detail. In addition, the origin of these antibodies is unknown. Here w e report that purified anti-disialosyl paraproteins from two affected patients bind a wide array of human peripheral nerve structures includ ing dorsal root ganglia, dorsal and ventral root axons, femoral and oc ulomotor nerves. We also show that these paraproteins bind lipopolysac charides of Campylobacter jejuni isolates from 3/3 cases of Miller Fis her syndrome, and to a less frequent extent, from cases of Guillain-Ba rre syndrome and enteritis controls. In conjunction with our previous studies, these data provide a possible causal link between the origin and pathogenic effects of anti-disialosyl antibodies in human paraprot einaemic neuropathy. (C) 1997 Elsevier Science B.V.