title: Paraproteins of familial MGUS/multiple myeloma target family-typical antigens: hyperphosphorylation of autoantigens is a consistent finding in familial and sporadic MGUS/MM.
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.
authors.affiliation: José-Carreras-Center for Immuno- and Gene Therapy, Department Internal Medicine I, Saarland University Medical School, Homburg/Saar, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Grass
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Preuss
authors.forename: Stephan
authors.initials: S
authors.lastname: Thome
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Weisenburger
authors.forename: Vinetta
authors.initials: V
authors.lastname: Witt
authors.forename: Jane
authors.initials: J
authors.lastname: Lynch
authors.forename: Florian
authors.initials: F
authors.lastname: Zettl
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.forename: Natalie
authors.initials: N
authors.lastname: Fadle
authors.forename: Evi
authors.initials: E
authors.lastname: Regitz
authors.forename: Henry
authors.initials: H
authors.lastname: Lynch
authors.forename: Michael
authors.initials: M
authors.lastname: Pfreundschuh
mesh_terms: D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism*; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D006579:Heterozygote; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000378:metabolism; D007074:Immunoglobulin G / Q000235:genetics / Q000378:metabolism; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism; D008297:Male; D009101:Multiple Myeloma / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D010266:Paraproteins / Q000235:genetics* / Q000378:metabolism*; D010375:Pedigree; D010766:Phosphorylation / Q000502:physiology; D015995:Prevalence; D040081:Protein Array Analysis; D012307:Risk Factors
chemical_list: D001324:Autoantigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010266:Paraproteins