An IgM anti-MBP Ab in a case of Waldenstrom's macroglobulinemia with polyneuropathy expressing an idiotype reactive with an MBP epitope immunodominant in MS and EAE.
In a previously described case of Waldenstrom's Macroglobulinemia, complicated by polyneuropathy, the IgM/lambda monoclonal antibody (mAb) was highly reactive with myelin basic protein (MBP). Given our demonstration that V lambda x, a recently described murine lambda variable region gene product, can itself bind MBP as well as confer MBP reactivity to an Ab, the possibility of a shared idiotypy between murine V lambda x and this human IgM/lambda anti-MBP was investigated. We characterized the epitope specificity of the macroglobulinemia patient's MBP-reactive IgM/lambda using indirect ELISA procedures with MBP, a citrullinated isomer of MBP termed C8, or peptide fragments of MBP as the coating antigens and monospecific Ab to V lambda x as the secondary Ab. The patient's MBP-reactive IgM/lambda was recognized by Ab specific for V lambda x and, like murine mAb containing V lambda x bound human MBP but not MBP-C8 nor other common autoantigens such as DNA, thyroglobulin, or actin. The anti-MBP reactivity was selective for MBP peptide 90-170 and preferentially recognized MBP peptide 84-96. Thus, the patient's macroglobulin and perhaps certain other human Ab with a 'V lambda x idiotype' bind to MBP peptide residues 84-96, an immunodominant peptide in multiple sclerosis patients. Such binding may be involved in the pathogenesis of neural damage in patients with neuroimmunologic disorders related to plasma cell dyscrasias or autoimmunity.
Noerager
B D
BD
Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Inuzuka
T
T
Kira
J
J
Blalock
J E
JE
Whitaker
J N
JN
Galin
F S
FS
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood*; D008259:Macroglobulins / Q000276:immunology; D009103:Multiple Sclerosis / Q000276:immunology*; D004676:Myelin Basic Protein / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D011115:Polyneuropathies / Q000276:immunology*; D011817:Rabbits; D008258:Waldenstrom Macroglobulinemia / Q000276:immunology*
D001323:Autoantibodies; D016056:Immunodominant Epitopes; D007075:Immunoglobulin M; D008259:Macroglobulins; D004676:Myelin Basic Protein; D010446:Peptide Fragments