HUMAN-IMMUNOGLOBULIN-M PARAPROTEINS CROSS-REACTIVE WITH NEISSERIA-MENINGITIDIS GROUP-B POLYSACCHARIDE AND FETAL BRAIN

Three hundred fifty-nine serum samples from patients with immunoglobul in M (IgM) or IgG monoclonal gammopathies were tested for binding to t he capsular polysaccharide (PS) of Neisseria meningitidis group B (Men B PS, poly-alpha[2-->8] -N-acetylneuraminic acid). Of 159 IgM paraprot eins, 7 (4.4%) were positive, compared with 0 of 200 IgG paraproteins (P < 0.05). Since MenB PS reactivity was limited to the IgM paraprotei ns, the 159 IgM paraproteins were tested by enzyme-linked immunosorben t assay (ELISA) for reactivity with seven other bacterial PSs. None re acted with meningococcal A or C, Haemophilus influenzae type b, or Str eptococcus pneumoniae type 3, 6, 14, or 23 PS. The specificity of the MenB PS-reactive antibodies was confirmed by demonstration of binding to N. meningitidis group B cells but not to a capsular PS-deficient mu tant and by specific inhibition of binding to solid-phase MenB PS by s oluble MenB PS in an ELISA. Five of five antibodies tested protected i nfant rats from bacteremia caused by Escherichia coli K1, an organism with a PS capsule that also is composed of poly-alpha[2-->8]-N-acetyln euraminic acid. Each of the seven MenB PS-reactive paraproteins had au toantibody activity as defined by binding to homogenates of calf brain in a radioimmunoassay. For six of the seven antibodies, binding to ca lf brain was inhibited by the addition of soluble MenB PS. Thus, appro ximately 4% of human IgM paraproteins have autoantibody activity to po ly-alpha [2-->8]-N-acetylneuraminic acid, an antigen expressed in feta l brain and cross-reactive with the MenB capsular PS. The reason for t his skewing of the IgM paraprotein repertoire toward reactivity with p oly-alpha [2-->8] -N-acetylneuraminic acid antigenic determinants is u nknown.