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Subsets of patients diagnosed with a monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM) or multiple myeloma (MM), present with a monoclonal immunoglobulin (Ig) specific for an infectious pathogen, including hepatitis C and B viruses (HCV, HBV), Helicobacter pylori and several Herpesviruses . Such cases are likely initiated by infection, since in the context of HCV- or HBV-infected patients, antiviral therapy can lead to the disappearance of antigenic stimulation, control of clonal plasma cells, and reduced or suppressed monoclonal Ig production. Complete remission has been obtained with anti-HCV therapy in refractory MM with a HCV-specific monoclonal Ig, and antiviral treatments significantly improved the probability of survival of MM patients infected with HCV or HBV prior to the diagnosis of MM. Monoclonal Igs may also target glucolipids, particularly glucosylsphingosine (GlcSph), and GlcSph-reducing therapy can lead to complete remission in SMM and MM patients presenting with a GlcSph-specific monoclonal Ig. The present review describes the importance of determining the target of the monoclonal Ig of MGUS, SMM and MM patients, and discusses the efficacy of target-reducing treatments in the management of MGUS, SMM and MM cases who present with a monoclonal Ig reactive against a treatable infectious pathogen or GlcSph.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Titel:	Determination of the target of monoclonal immunoglobulins: a novel diagnostic tool for individualized MGUS therapy, and prevention and therapy of smoldering and multiple myeloma.
Autor/in / Beteiligte Person:	Hermouet, S ; Bigot-Corbel, E ; Harb, J
Link:	Full Text Finder (Volltext)
Zeitschrift:	Frontiers in immunology, Jg. 14 (2023-10-31), S. 1253363
Veröffentlichung:	[Lausanne : Frontiers Research Foundation], 2023
Medientyp:	academicJournal
ISSN:	1664-3224 (electronic)
DOI:	10.3389/fimmu.2023.1253363
Schlagwort:	Humans Paraproteins Antibodies, Monoclonal therapeutic use Multiple Myeloma diagnosis Multiple Myeloma therapy Monoclonal Gammopathy of Undetermined Significance diagnosis Smoldering Multiple Myeloma Hepatitis C
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Review Language: English [Front Immunol] 2023 Oct 31; Vol. 14, pp. 1253363. <i>Date of Electronic Publication: </i>2023 Oct 31 (<i>Print Publication: </i>2023). MeSH Terms: Multiple Myeloma* / diagnosis ; Multiple Myeloma* / therapy ; Monoclonal Gammopathy of Undetermined Significance* / diagnosis ; Smoldering Multiple Myeloma* ; Hepatitis C* ; Humans ; Paraproteins ; Antibodies, Monoclonal / therapeutic use References: Am J Gastroenterol. 2002 Jun;97(6):1371-4. (PMID: 12094852) ; J Neurol. 2015 Mar;262(3):666-73. (PMID: 25549972) ; Int J Cancer. 2014 Apr 1;134(7):1734-40. (PMID: 24105662) ; Clin Chem. 2009 Sep;55(9):1646-55. (PMID: 19617289) ; Front Immunol. 2022 Jul 25;13:925266. (PMID: 35958625) ; J Exp Med. 2013 Jan 14;210(1):59-70. (PMID: 23296468) ; Medicine (Baltimore). 1999 Jul;78(4):228-35. (PMID: 10424205) ; Haematologica. 2022 Sep 01;107(9):2037-2050. (PMID: 35770530) ; Haematologica. 2023 May 18;:. (PMID: 37199121) ; J Neuroimmunol. 1998 Apr 15;84(2):117-21. (PMID: 9628452) ; Curr Treat Options Neurol. 2017 Oct 16;19(12):43. (PMID: 29034435) ; Cancers (Basel). 2020 May 15;12(5):. (PMID: 32429322) ; N Engl J Med. 2003 Jan 9;348(2):178-9. (PMID: 12519936) ; Ann Hematol. 2009 Aug;88(8):769-73. (PMID: 19159929) ; Eur J Cancer. 2018 Nov;103:356-387. (PMID: 30100160) ; Proc Natl Acad Sci U S A. 1984 Feb;81(4):1225-9. (PMID: 6199795) ; JCI Insight. 2018 Apr 19;3(8):. (PMID: 29669929) ; Front Immunol. 2022 Apr 28;13:876271. (PMID: 35572590) ; Anal Biochem. 2013 Feb 15;433(2):202-9. (PMID: 23103342) ; Lancet Oncol. 2014 Nov;15(12):e538-48. (PMID: 25439696) ; J Neurochem. 1990 May;54(5):1569-75. (PMID: 1691277) ; Biosci Rep. 2019 Oct 30;39(10):. (PMID: 30967494) ; Blood. 2018 Oct 4;132(14):1478-1485. (PMID: 30012636) ; Front Immunol. 2020 May 27;11:854. (PMID: 32536913) ; J Pathol. 2015 Jan;235(1):113-24. (PMID: 25256118) ; Leukemia. 2003 Jan;17(1):185-95. (PMID: 12529677) ; Front Immunol. 2022 Jan 11;12:797209. (PMID: 35087522) ; JCI Insight. 2017 Oct 5;2(19):. (PMID: 28978808) ; Br J Haematol. 2022 Aug;198(4):641-653. (PMID: 35514140) ; In Vivo. 2021 Nov-Dec;35(6):3289-3296. (PMID: 34697160) ; Haematologica. 2016 Dec;101(12):1460-1468. (PMID: 27903713) ; Haematologica. 2023 Jul 20;:. (PMID: 37470153) ; Blood. 2008 Nov 15;112(10):4357-8. (PMID: 18988883) ; N Engl J Med. 2016 Feb 11;374(6):555-61. (PMID: 26863356) ; Cell Mol Life Sci. 2016 Apr;73(8):1569-89. (PMID: 26801219) ; Methods Mol Biol. 2019;1956:1-33. (PMID: 30779028) ; Mol Genet Metab. 2020 Apr;129(4):286-291. (PMID: 32044242) ; Chem Phys Lipids. 1986 Dec 15;42(1-3):235-48. (PMID: 2435424) ; Lancet Haematol. 2022 May;9(5):e340-e349. (PMID: 35344689) ; Ann Diagn Pathol. 2017 Apr;27:1-6. (PMID: 28325354) ; Am J Transplant. 2011 Oct;11(10):2144-52. (PMID: 21827616) ; J Neurol Sci. 2000 Jun 15;176(2):144-50. (PMID: 10930598) ; Haematologica. 2023 Jun 01;108(6):1476-1486. (PMID: 36373250) ; Leuk Res Rep. 2013 May 17;2(1):39-40. (PMID: 24371776) ; Br J Haematol. 2019 Feb;184(3):384-391. (PMID: 30450574) ; Hematology Am Soc Hematol Educ Program. 2017 Dec 8;2017(1):194-204. (PMID: 29222256) ; Cells. 2021 Feb 19;10(2):. (PMID: 33669483) ; Eur J Neurol. 2017 Nov;24(11):1334-1340. (PMID: 28782863) ; Front Immunol. 2022 Jun 30;13:960829. (PMID: 35844583) ; Blood. 2022 Feb 10;139(6):946-950. (PMID: 34871382) ; Ann Hematol. 2022 Mar;101(3):491-511. (PMID: 34994811) ; Front Immunol. 2017 Oct 19;8:1347. (PMID: 29098000) ; Cancer Treat Res. 2014;161:319-49. (PMID: 24706230) ; Brain. 2001 Oct;124(Pt 10):1968-77. (PMID: 11571215) ; Blood Cancer J. 2023 Jan 4;13(1):1. (PMID: 36599831) ; Am J Kidney Dis. 2005 Feb;45(2):397-406. (PMID: 15685519) ; Eur J Haematol. 2021 Mar;106(3):380-388. (PMID: 33295006) ; Blood Adv. 2023 Aug 8;7(15):3932-3935. (PMID: 37196639) ; J Viral Hepat. 2017 Dec;24(12):1151-1159. (PMID: 28656736) ; Blood Cancer J. 2019 Dec 13;9(12):102. (PMID: 31836698) Contributed Indexing: Keywords: glucosylsphingosine (GlcSph); infectious pathogens; monoclonal gammopathy of undetermined significance (MGUS); monoclonal immunoglobulin; multiple myeloma (MM); smoldering multiple myeloma (SMM); therapeutic targets; therapy Substance Nomenclature: 52050-17-6 (sphingosyl beta-glucoside) ; 0 (Paraproteins) ; 0 (Antibodies, Monoclonal) Entry Date(s): Date Created: 20231129 Date Completed: 20231201 Latest Revision: 20240320 Update Code: 20240321 PubMed Central ID: PMC10644846

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Determination of the target of monoclonal immunoglobulins: a novel diagnostic tool for individualized MGUS therapy, and prevention and therapy of smoldering and multiple myeloma.