A frequent target of paraproteins in the sera of patients with multiple myeloma and MGUS.
Antigenic targets of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) paraproteins might play a role in the pathogenesis of these neoplasms. We screened a human fetal brain-derived macroarray with the IgA or IgG containing sera of 192 consecutive MGUS and MM patients. Twenty-nine of 192 (15.1%) paraproteins reacted with paratarg-7, a protein of unknown function which is expressed in all human tissues. Paratarg-7 reactivity was similarly frequent among IgA and IgG paraproteins, but all paratarg-7 reactive IgG paraproteins belonged to the IgG3 subtype with 24/57 IgG3 (42.1%) paraproteins displaying this specificity. Sequence analysis of paratarg-7 derived from patients having a paraprotein with specificity for paratarg-7 revealed no differences to paratarg-7 derived from patients with paraproteins of other specificities or healthy controls, excluding mutations or polymorphisms as a reason for its autoimmunogenicity. Similarly, Western-blot analysis showed identical bands for paratarg-7 derived from patients and controls. The above-random frequency of paratarg-7 as a paraprotein target suggests that paratarg-7 might be involved in the development of the respective clonal proliferations. The identification of paratarg-7 as an antigenic target enables the more detailed analysis of tumor-host interactions in these patients and their role in the pathogenesis of MM and MGUS.
Preuss
Klaus-Dieter
KD
José-Carreras-Center for Immuno- and Gene Therapy, Department of Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany.
Pfreundschuh
Michael
M
Ahlgrimm
Manfred
M
Fadle
Natalie
N
Regitz
Evi
E
Murawski
Niels
N
Grass
Sandra
S
D001798:Blood Proteins / Q000276:immunology*; D015153:Blotting, Western; D004586:Electrophoresis; D005500:Follow-Up Studies; D006801:Humans; D015151:Immunoblotting; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008565:Membrane Proteins / Q000276:immunology*; D009101:Multiple Myeloma / Q000276:immunology*; D010265:Paraproteinemias / Q000276:immunology*; D010266:Paraproteins / Q000276:immunology*
D001798:Blood Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008565:Membrane Proteins; D010266:Paraproteins; C406287:STOML2 protein, human