Paraproteins of familial MGUS/multiple myeloma target family-typical antigens: Hyperphosphorylation of autoantigens is a consistent finding in familial and sporadic MGUS/MM

Sandra Grass, Klaus Dieter Preuss, Stephan Thome, Dennis D. Weisenburger, Vinetta Witt, Jane Lynch, Florian Zettl, Lorenz Trümper, Natalie Fadle, Evi Regitz, Henry T. Lynch, Michael Pfreundschuh

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Abstract

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.

Original languageEnglish
Pages (from-to)635-637
Number of pages3
JournalBlood
Volume118
Issue number3
DOIs
StatePublished - Jul 21 2011

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Monoclonal Gammopathy of Undetermined Significance
Paraproteins
Autoantigens
Multiple Myeloma
Antigens
Carrier State
Waldenstrom Macroglobulinemia
Genes

All Science Journal Classification (ASJC) codes

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Paraproteins of familial MGUS/multiple myeloma target family-typical antigens : Hyperphosphorylation of autoantigens is a consistent finding in familial and sporadic MGUS/MM. / Grass, Sandra; Preuss, Klaus Dieter; Thome, Stephan; Weisenburger, Dennis D.; Witt, Vinetta; Lynch, Jane; Zettl, Florian; Trümper, Lorenz; Fadle, Natalie; Regitz, Evi; Lynch, Henry T.; Pfreundschuh, Michael.

In: Blood, Vol. 118, No. 3, 21.07.2011, p. 635-637.

Research output: Contribution to journalArticle

Grass, S, Preuss, KD, Thome, S, Weisenburger, DD, Witt, V, Lynch, J, Zettl, F, Trümper, L, Fadle, N, Regitz, E, Lynch, HT & Pfreundschuh, M 2011, 'Paraproteins of familial MGUS/multiple myeloma target family-typical antigens: Hyperphosphorylation of autoantigens is a consistent finding in familial and sporadic MGUS/MM', Blood, vol. 118, no. 3, pp. 635-637. https://doi.org/10.1182/blood-2011-01-331454
Grass, Sandra ; Preuss, Klaus Dieter ; Thome, Stephan ; Weisenburger, Dennis D. ; Witt, Vinetta ; Lynch, Jane ; Zettl, Florian ; Trümper, Lorenz ; Fadle, Natalie ; Regitz, Evi ; Lynch, Henry T. ; Pfreundschuh, Michael. / Paraproteins of familial MGUS/multiple myeloma target family-typical antigens : Hyperphosphorylation of autoantigens is a consistent finding in familial and sporadic MGUS/MM. In: Blood. 2011 ; Vol. 118, No. 3. pp. 635-637.
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abstract = "Paratarg-7 (P-7) is a frequent paraprotein target in monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), and Waldenstr{\"o}m 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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AU - Weisenburger, Dennis D.

AU - Witt, Vinetta

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AU - Zettl, Florian

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