Identification of antigenic targets of paraproteins by expression cloning does not support a causal role of chronic antigenic stimulation in the pathogenesis of multiple myeloma and MGUS.
Antigenic targets of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) paraproteins have been suggested to play an important role as growth stimulators in the pathogenesis of these neoplasms. To identify such targets, we screened cDNA libraries from human testis, lung and breast cancer, bovine and porcine muscle and wheat germ for reactivity with paraproteins in the sera from 115 patients with MGUS and MM. Of >6 x 10(8) paraprotein-antigen interactions screened, an IgA paraprotein from a female patient bound to sperm-specific cylicin-2, and 3 IgG paraproteins bound to tripeptidyl-peptidase-II (TPP-2), insulin-like growth-factor binding-protein-2 (IGFBP-2) and porcine kinesin. Specificity was confirmed by reverse Western blots using recombinant antigens. The broad spectrum of auto-, allo- and heteroantigens as targets of human paraproteins in patients without signs of chronic antigenic stimulation renders a causal role of the antigenic stimulus in the pathogenesis of MGUS and MM unlikely.
Preuss
Klaus-Dieter
KD
Klinik für Innere Medizin I, Saarland University Medical School, Homburg/Saar, Germany.
Held
Gerhard
G
Kubuschok
Boris
B
Hung
Chun-Zhu
CZ
Malatsidze
Natalia
N
Wagner
Mathias
M
Pfreundschuh
Michael
M
D000626:Aminopeptidases; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western / Q000379:methods; D002417:Cattle; D003001:Cloning, Molecular; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D005260:Female; D015723:Gene Library; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000276:immunology; D016547:Kinesins / Q000276:immunology; D008297:Male; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology* / Q000473:pathology; D010265:Paraproteinemias / Q000097:blood / Q000276:immunology* / Q000473:pathology; D010266:Paraproteins / Q000276:immunology*; D012697:Serine Endopeptidases / Q000276:immunology; D013552:Swine
D000941:Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D018971:Insulin-Like Growth Factor Binding Protein 2; D010266:Paraproteins; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases; D016547:Kinesins