Human immunoglobulin M paraproteins cross-reactive with Neisseria meningitidis group B polysaccharide and fetal brain.
Three hundred fifty-nine serum samples from patients with immunoglobulin M (IgM) or IgG monoclonal gammopathies were tested for binding to the capsular polysaccharide (PS) of Neisseria meningitidis group B (MenB PS, poly-alpha[2-->8]-N-acetylneuraminic acid). Of 159 IgM paraproteins, 7 (4.4%) were positive, compared with 0 of 200 IgG paraproteins (P < 0.05). Since MenB PS reactivity was limited to the IgM paraproteins, the 159 IgM paraproteins were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with seven other bacterial PSs. None reacted with meningococcal A or C, Haemophilus influenzae type b, or Streptococcus 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 mutant and by specific inhibition of binding to solid-phase MenB PS by soluble MenB PS in an ELISA. Five of five antibodies tested protected infant rats from bacteremia caused by Escherichia coli K1, an organism with a PS capsule that also is composed of poly-alpha[2-->8]-N-acetylneuraminic acid. Each of the seven MenB PS-reactive paraproteins had autoantibody activity as defined by binding to homogenates of calf brain in a radioimmunoassay. For six of the seven antibodies, binding to calf brain was inhibited by the addition of soluble MenB PS. Thus, approximately 4% of human IgM paraproteins have autoantibody activity to poly-alpha[2-->8]-N-acetylneuraminic acid, an antigen expressed in fetal brain and cross-reactive with the MenB capsular PS. The reason for this skewing of the IgM paraprotein repertoire toward reactivity with poly-alpha[2-->8]-N-acetylneuraminic acid antigenic determinants is unknown.
Azmi
F H
FH
Children's Hospital Oakland Research Institute, CA 94609, USA.
Lucas
A H
AH
Spiegelberg
H L
HL
Granoff
D M
DM
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000907:Antibodies, Bacterial / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D016470:Bacteremia / Q000276:immunology / Q000517:prevention & control; D016667:Bacterial Capsules / Q000145:classification / Q000276:immunology*; D001921:Brain / Q000276:immunology*; D003429:Cross Reactions; D004927:Escherichia coli Infections / Q000276:immunology / Q000517:prevention & control; D005333:Fetus / Q000276:immunology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D010266:Paraproteins; D011061:Poly A / Q000276:immunology; D011750:Pyroglobulins / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012794:Sialic Acids / Q000276:immunology; D013045:Species Specificity
D000888:Antibodies, Anti-Idiotypic; D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; C001437:IgM-L paraprotein; D007075:Immunoglobulin M; D010266:Paraproteins; D011750:Pyroglobulins; D012794:Sialic Acids; C038718:neural cell surface antigen BSP-2; D011061:Poly A