Hyperphosphorylated paratarg-7: a new molecularly defined risk factor for monoclonal gammopathy of undetermined significance of the IgM type and Waldenstrom macroglobulinemia
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 Waldenström 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.
%0 Journal Article
%1 Grass.2011b
%A Grass, Sandra
%A Preuss, Klaus-Dieter
%A Wikowicz, Alexandra
%A Terpos, Evangelos
%A Ziepert, Marita
%A Nikolaus, Diana
%A Yang, Yin
%A Fadle, Natalie
%A Regitz, Evi
%A Dimopoulos, Meletios A.
%A Treon, Steven P.
%A Hunter, Zachary R.
%A Pfreundschuh, Michael
%D 2011
%J Blood
%K Antibody_Specificity Blood_Proteins/metabolism Blotting,_Western Enzyme-Linked_Immunosorbent_Assay Female Genetic_Predisposition_to_Disease Heterozygote Humans Immunoglobulin_M/immunology Male Membrane_Proteins/metabolism Middle_Aged Paraproteinemias/genetics/immunology/metabolism Pedigree Phosphorylation Polymerase_Chain_Reaction Risk_Factors Waldenstrom_Macroglobulinemia/genetics/immunology/metabolism
%N 10
%P 2918–2923
%T Hyperphosphorylated paratarg-7: a new molecularly defined risk factor for monoclonal gammopathy of undetermined significance of the IgM type and Waldenstrom macroglobulinemia
%V 117
%X 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 Waldenström 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.
@article{Grass.2011b,
abstract = {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 Waldenström 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.},
added-at = {2014-10-14T15:27:58.000+0200},
author = {Grass, Sandra and Preuss, Klaus-Dieter and Wikowicz, Alexandra and Terpos, Evangelos and Ziepert, Marita and Nikolaus, Diana and Yang, Yin and Fadle, Natalie and Regitz, Evi and Dimopoulos, Meletios A. and Treon, Steven P. and Hunter, Zachary R. and Pfreundschuh, Michael},
biburl = {https://www.bibsonomy.org/bibtex/2301f8027ea959cee2077993c5071f68d/drtester},
interhash = {a7677818dca197923497b60a02ea3d1f},
intrahash = {301f8027ea959cee2077993c5071f68d},
journal = {Blood},
keywords = {Antibody_Specificity Blood_Proteins/metabolism Blotting,_Western Enzyme-Linked_Immunosorbent_Assay Female Genetic_Predisposition_to_Disease Heterozygote Humans Immunoglobulin_M/immunology Male Membrane_Proteins/metabolism Middle_Aged Paraproteinemias/genetics/immunology/metabolism Pedigree Phosphorylation Polymerase_Chain_Reaction Risk_Factors Waldenstrom_Macroglobulinemia/genetics/immunology/metabolism},
number = 10,
pages = {2918–2923},
timestamp = {2014-10-14T15:27:58.000+0200},
title = {Hyperphosphorylated paratarg-7: a new molecularly defined risk factor for monoclonal gammopathy of undetermined significance of the IgM type and Waldenstrom macroglobulinemia},
volume = 117,
year = 2011
}