Avidity distribution of antibodies against peripheral nerve myelin in patients with polyneuropathy associated with IgM monoclonal gammopathy and in healthy controls.
To elucidate the role and nature of antibodies against peripheral nerve myelin (PNM) we studied their avidity distribution. Twelve patients with demyelinating polyneuropathy associated with IgM monoclonal gammopathy were compared with 12 healthy blood donors previously found to have anti-PNM antibodies of IgM isotype. For comparison, the avidity distribution of IgM antibodies against the varicella zoster antigen in 10 patients with herpes zoster infection was also studied. Microtitre plates containing antibody bound to antigen were exposed to increasing concentrations of sodium thiocyanate (NaSCN) followed by an ELISA assay. NaSCN changes the ion strength and the pH, and thereby the critical conditions for antibody-antigen binding. Resistance to NaSCN was used as a measure of antibody avidity. Anti-PNM antibodies from patients with monoclonal gammopathy were of predominantly low avidity whereas antibodies from blood donors were of predominantly high avidity. Avidity index, representing the molar concentration of NaSCN required to reduce the initial absorbance values by 50%, was on average 11.7 times higher in blood donors (range 0.24-2.65, mean = 0.82) than in patients with monoclonal gammopathy (range 0.04-0.10, mean = 0.07) (p = 0.002). On the other hand, patients with monoclonal gammopathy had on average a 100-fold higher relative concentration of antibodies against PNM compared to blood donors (range 4.1-392.6 AU, mean 85.0 AU, and range 0.2-1.7 AU, mean 0.85 AU, respectively) (p = 0.002). Antibodies against the varicella zoster antigen from patients with herpes zoster showed a high avidity index (range 0.25-2.6, mean = 1.24). Using Western blot, several 14-30 kDa proteins in PNM were found to be the target antigen for IgM anti-PNM antibodies in both patients with monoclonal gammopathy and polyneuropathy, and in blood donors.(ABSTRACT TRUNCATED AT 250 WORDS)
Vrethem
M
M
Department of Neurology, University Hospital, Linköping, Sweden.
Ekerfelt
C
C
Ernerudh
J
J
D000368:Aged; D000369:Aged, 80 and over; D000915:Antibody Affinity / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007075:Immunoglobulin M / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D009185:Myelin Proteins / Q000276:immunology*; D010265:Paraproteinemias / Q000276:immunology*; D010523:Peripheral Nervous System Diseases / Q000276:immunology*; D012965:Sodium Chloride; D013861:Thiocyanates / Q000494:pharmacology
D007075:Immunoglobulin M; D009185:Myelin Proteins; D013861:Thiocyanates; D012965:Sodium Chloride; C024553:sodium thiocyanate