Increased T regulatory cells are associated with adverse
clinical features and predict progression in multiple myeloma.

J 2012

Increased T regulatory cells are associated with adverse clinical features and predict progression in multiple myeloma.

MUTHU RAJA, Karthick Raja; Lucie ŘÍHOVÁ; Lenka ZAHRADOVÁ; Mária KLINCOVÁ; Miroslav PENKA et. al.

Základní údaje

Originální název

Increased T regulatory cells are associated with adverse clinical features and predict progression in multiple myeloma.

Autoři

MUTHU RAJA, Karthick Raja (356 Indie, domácí); Lucie ŘÍHOVÁ (203 Česká republika, domácí); Lenka ZAHRADOVÁ (203 Česká republika); Mária KLINCOVÁ (703 Slovensko); Miroslav PENKA (203 Česká republika) a Roman HÁJEK (203 Česká republika, garant, domácí)

Vydání

PLOS ONE, San Francisco, Public Library of Science, 2012, 1932-6203

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Full Text

Impakt faktor

Impact factor: 3.730

Kód RIV

RIV/00216224:14110/12:00057825

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1371/journal.pone.0047077

UT WoS

000312385200077

EID Scopus

2-s2.0-84867372743

Klíčová slova anglicky

Regulatory T cells; multiple myeloma; dexamethasone; immune system

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 17. 12. 2019 15:39, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

Background: Regulatory T (Treg) cells play an important role in the maintenance of immune system homeostasis. Multiple myeloma (MM) is a plasma cell disorder frequently associated with impaired immune cell numbers and functions. Methods: We analyzed Treg cells in peripheral blood (n = 207) and bone marrow (n = 202) of pre-malignant and malignant MM patients using flow cytometry. Treg cells and their subsets from MM patients and healthy volunteers were functionally evaluated for their suppressive property. A cohort of 25 patients was analyzed for lymphocytes, CD4 T cells and Treg cells before and after treatment with cyclophosphamide, thalidomide plus dexamethasone (CTD). Results: We found elevated frequencies of Treg cells in newly diagnosed (P<0.01) and relapsed MM patients (P<0.0001) compared to healthy volunteers. Also, Treg subsets including naive (P = 0.015) and activated (P = 0.036) Treg cells were significantly increased in MM patients compared to healthy volunteers. Functional studies showed that Treg cells and their subsets from both MM and healthy volunteers were similar in their inhibitory function. Significantly increased frequencies of Treg cells were found in MM patients with adverse clinical features such as hypercalcemia (.10 mg/dL), decreased normal plasma cell (<5%) count and IgA myeloma subtype. We also showed that MM patients with >5% of Treg cells had inferior time to progression (TTP) (13 months vs. median not reached; P = 0.013). Furthermore, we demonstrated the prognostic value of Treg cells in prediction of TTP by Cox regression analysis (P = 0.045). CTD treatment significantly reduced frequencies of CD4 T cells (P = 0.001) and Treg cells (P = 0.018) but not Treg cells/CD4 T cells ratio compared to pretreatment. Conclusions: Our study showed immune deregulation in MM patients which is evidenced by elevated level of functionally active Treg cells and patients with increased Treg cells have higher risk of progression.

Návaznosti

GAP304/10/1395, projekt VaV

Název: Analýza klonálních progenitorů plazmatických buněk u monoklonálních gamapatií

Investor: Grantová agentura ČR, Analýza klonálních progenitorů plazmatických buněk u monoklonálních gamapatií

MSM0021622434, záměr

Název: Od klasických prognostických markerů ke klinicky aplikovatelným farmakogenomickým a farmakoproteomickým projektům u mnohočetného myelomu a monoklonálních gamapatií

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Od klasických prognostických markerů ke klinicky aplikovatelným farmakogenomickým a farmakoproteomickým projektům u mnohočetného myelomu a monoklonálních gamapatií

Přiložené soubory

Muthu_Raja_2012_-_PLoS_ONE.pdf

Citovat

MUTHU RAJA, Karthick Raja; Lucie ŘÍHOVÁ; Lenka ZAHRADOVÁ; Mária KLINCOVÁ; Miroslav PENKA a Roman HÁJEK. Increased T regulatory cells are associated with adverse clinical features and predict progression in multiple myeloma. PLOS ONE. San Francisco: Public Library of Science, 2012, roč. 7, č. 10, s. 1-11. ISSN 1932-6203. Dostupné z: https://doi.org/10.1371/journal.pone.0047077.

@article{1074133,
   author = {Muthu Raja, Karthick Raja and Říhová, Lucie and Zahradová, Lenka and Klincová, Mária and Penka, Miroslav and Hájek, Roman},
   article_location = {San Francisco},
   article_number = {10},
   doi = {https://doi.org/10.1371/journal.pone.0047077},
   keywords = {Regulatory T cells; multiple myeloma; dexamethasone; immune system},
   language = {eng},
   issn = {1932-6203},
   journal = {PLOS ONE},
   note = {Art. no e47077},
   title = {Increased T regulatory cells are associated with adverse clinical features and predict progression in multiple myeloma.},
   url = {http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047077},
   volume = {7},
   year = {2012}
}

TY  - JOUR
ID  - 1074133
AU  - Muthu Raja, Karthick Raja - Říhová, Lucie - Zahradová, Lenka - Klincová, Mária - Penka, Miroslav - Hájek, Roman
PY  - 2012
TI  - Increased T regulatory cells are associated with adverse clinical features and predict progression in multiple myeloma.
JF  - PLOS ONE
VL  - 7
IS  - 10
SP  - 1-11
EP  - 1-11
PB  - Public Library of Science
SN  - 19326203
N1  - Art. no e47077
KW  - Regulatory T cells
KW  - multiple myeloma
KW  - dexamethasone
KW  - immune system
UR  - http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047077
L2  - http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0047077
N2  - Background: Regulatory T (Treg) cells play an important role in the maintenance of immune system homeostasis. Multiple myeloma (MM) is a plasma cell disorder frequently associated with impaired immune cell numbers and functions. Methods: We analyzed Treg cells in peripheral blood (n = 207) and bone marrow (n = 202) of pre-malignant and malignant MM patients using flow cytometry. Treg cells and their subsets from MM patients and healthy volunteers were functionally evaluated for their suppressive property. A cohort of 25 patients was analyzed for lymphocytes, CD4 T cells and Treg cells before and after treatment with cyclophosphamide, thalidomide plus dexamethasone (CTD). Results: We found elevated frequencies of Treg cells in newly diagnosed (P<0.01) and relapsed MM patients (P<0.0001) compared to healthy volunteers. Also, Treg subsets including naive (P = 0.015) and activated (P = 0.036) Treg cells were significantly increased in MM patients compared to healthy volunteers. Functional studies showed that Treg cells and their subsets from both MM and healthy volunteers were similar in their inhibitory function. Significantly increased frequencies of Treg cells were found in MM patients with adverse clinical features such as hypercalcemia (.10 mg/dL), decreased normal plasma cell (<5%) count and IgA myeloma subtype. We also showed that MM patients with >5% of Treg cells had inferior time to progression (TTP) (13 months vs. median not reached; P = 0.013). Furthermore, we demonstrated the prognostic value of Treg cells in prediction of TTP by Cox regression analysis (P = 0.045). CTD treatment significantly reduced frequencies of CD4 T cells (P = 0.001) and Treg cells (P = 0.018) but not Treg cells/CD4 T cells ratio compared to pretreatment. Conclusions: Our study showed immune deregulation in MM patients which is evidenced by elevated level of functionally active Treg cells and patients with increased Treg cells have higher risk of progression.
ER  -

MUTHU RAJA, Karthick Raja; Lucie ŘÍHOVÁ; Lenka ZAHRADOVÁ; Mária KLINCOVÁ; Miroslav PENKA a Roman HÁJEK. Increased T regulatory cells are associated with adverse clinical features and predict progression in multiple myeloma. \textit{PLOS ONE}. San Francisco: Public Library of Science, 2012, roč.~7, č.~10, s.~1-11. ISSN~1932-6203. Dostupné z: https://doi.org/10.1371/journal.pone.0047077.

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