Περίληψη:
We recently described paratarg-7 (P-7), a protein of unknown function,
as the target of 15% of immunoglobulin A (IgA) and IgG paraproteins in
monoclonal gammopathy of undetermined significance (MGUS) and multiple
myeloma. To determine the frequency of P-7 as a paraprotein target in
IgM-MGUS and Waldenstrom macroglobulinemia (WM), sera from patients with
IgM-MGUS/WM were tested for reactivity with recombinant P-7 by
enzyme-linked immunoabsorbent assay. The specificity of the
paraprotein-mediated reaction was shown by absorption studies and
cloning of the respective B-cell receptor. The paraproteins of 18 (9 WM
and 9 IgM-MGUS) of 161 patients (11%) reacted with P-7. Isoelectric
focusing and phosphatase treatment showed that P-7 was
hyperphosphorylated (pP-7) in all patients with an anti-P-7-specific IgM
paraprotein tested. Because only 4 of 200 healthy controls (2%) were
carriers of pP-7, pP-7 carrier state is associated with a significantly
increased risk (odds ratio = 6.2; P = .001) for developing IgM-MGUS/MW.
Family analyses showed that the pP-7 carrier state is inherited as a
dominant trait. After IgA/IgG-MGUS and multiple myeloma, IgM-MGUS/WM is
the second neoplasia associated with pP-7 carrier state. The dominant
inheritance of pP-7 explains cases of familial IgM-MGUS/WM and enables
the identification of family members at increased risk. (Blood.
2011;117(10):2918-2923)
Συγγραφείς:
Grass, Sandra
Preuss, Klaus-Dieter
Wikowicz, Alexandra and
Terpos, Evangelos
Ziepert, Marita
Nikolaus, Diana
Yang, Yin
and Fadle, Natalie
Regitz, Evi
Dimopoulos, Meletios A. and
Treon, Steven P.
Hunter, Zachary R.
Pfreundschuh, Michael
