TY - JOUR
T1 - Paraproteins of familial MGUS/multiple myeloma target family-typical antigens
T2 - Hyperphosphorylation of autoantigens is a consistent finding in familial and sporadic MGUS/MM
AU - Grass, Sandra
AU - Preuss, Klaus Dieter
AU - Thome, Stephan
AU - Weisenburger, Dennis D.
AU - Witt, Vinetta
AU - Lynch, Jane
AU - Zettl, Florian
AU - Trümper, Lorenz
AU - Fadle, Natalie
AU - Regitz, Evi
AU - Lynch, Henry
AU - Pfreundschuh, Michael
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/7/21
Y1 - 2011/7/21
N2 - Paratarg-7 (P-7) is a frequent paraprotein target in monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), and Waldenström macroglobulinemia. Patients with P-7-specific paraproteins carry a hyperphosphorylated paratarg-7 (pP-7). Because pP-7 carrier state is dominantly inherited, we determined the paraprotein targets in 4 families with familial MGUS/MM. No antigenic target was identified for the paraproteins from 2 members of one family. Paraproteins from affected members of 2 other families targeted P-7, and paraproteins from 4 affected members of a fourth family targeted P-8, which is encoded by the ATG13 gene. P-8 was hyperphosphorylated in the affected family members (pP-8) and pP-8 carrier state is inherited in a dominant fashion. Six additional autoantigenic nonfamilial paraprotein targets were also hyperphosphorylated in the respective patients compared with normal controls. We conclude that paraproteins of affected members with familial MGUS/MM share family-typical hyperphosphorylated antigens and hyperphosphorylation of paraprotein targets might be a general mechanism underlying the pathogenesis of MGUS/MM.
AB - Paratarg-7 (P-7) is a frequent paraprotein target in monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), and Waldenström macroglobulinemia. Patients with P-7-specific paraproteins carry a hyperphosphorylated paratarg-7 (pP-7). Because pP-7 carrier state is dominantly inherited, we determined the paraprotein targets in 4 families with familial MGUS/MM. No antigenic target was identified for the paraproteins from 2 members of one family. Paraproteins from affected members of 2 other families targeted P-7, and paraproteins from 4 affected members of a fourth family targeted P-8, which is encoded by the ATG13 gene. P-8 was hyperphosphorylated in the affected family members (pP-8) and pP-8 carrier state is inherited in a dominant fashion. Six additional autoantigenic nonfamilial paraprotein targets were also hyperphosphorylated in the respective patients compared with normal controls. We conclude that paraproteins of affected members with familial MGUS/MM share family-typical hyperphosphorylated antigens and hyperphosphorylation of paraprotein targets might be a general mechanism underlying the pathogenesis of MGUS/MM.
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U2 - 10.1182/blood-2011-01-331454
DO - 10.1182/blood-2011-01-331454
M3 - Article
C2 - 21586751
AN - SCOPUS:79960682231
SN - 0006-4971
VL - 118
SP - 635
EP - 637
JO - Blood
JF - Blood
IS - 3
ER -