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The impact of conventional DMARD and biological therapies on CD4+ cell subsets in rheumatoid arthritis: a follow-up study

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Abstract

Rheumatoid arthritis (RA) is an autoimmune disease characterized by abnormal prevalence of Th1, Th2, Th17, and regulatory (Treg) subsets. Some data suggest that these subsets are influenced by anti-RA agents. Follow-up studies monitoring T cell phenotype in response to therapy are limited. We investigated the alteration of CD4+ T cell subset distribution after the initiation of disease-modifying antirheumatic drug (DMARD) (with glucocorticosteroid (GCS) and methotrexate (MTX)) and anti-TNFα therapy. We enrolled 19 treatment naive (early) RA patients and initiated GCS (in a dose of 16 mg/day for 4 weeks; then 8 mg/day). MTX, 10 mg/week, was started at week 4. We also enrolled 32 RA patients unresponsive to DMARD and initiated anti-TNFα therapy: adalimumab (ADA), 40 mg/2 weeks, n = 12; etanercept (ETA), 50 mg/weeks, n = 12; or infliximab (IFX) on week 0, 2, and 6, 3 mg/kg bw, n = 8. Blood was taken before and 4 and 8 weeks after the initiation of therapy. Ten volunteers served as controls. The T cell phenotype was assessed with flow cytometry. In early RA, Th1, Th2, and Th17 prevalence was higher, while Treg prevalence was lower than normal. GCS alone decreased Th2 prevalence. GCS + MTX decreased Th17 prevalence. Immune phenotype in unresponsive RA before anti-TNF therapy was as in early RA. Four and 8 weeks after initiating anti-TNF therapy, Th1 prevalence was higher than baseline in ETA or IFX, while it was stable in ADA groups. Th2 prevalence was higher than normal in ADA or IFX, while normalized in ETA group. In each group, Treg prevalence increased, while Th17 prevalence was at the baseline. The proinflammatory immune phenotype is normalized only under GCS + MTX combination in early RA. Anti-TNFα therapy exhibit marked effects on all the cell populations investigated (except Th17); some slight differences in this action exist between ADA, ETA, and IFX therapy.

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Abbreviations

ADA:

Adalimumab

CRP:

C-reactive protein

DMARD:

Disease-modifying antirheumatic drug

ESR:

Erythrocyte sedimentation rate

ETA:

Etanercept

GCS:

Glucocorticoid

IFX:

Infliximab

LF:

Leflunomide

MCV:

Mutated citrullinated vimentin

MTX:

Methotrexate

NSAID:

Nonsteroidal antiinflammatory drug

PBMC:

Peripheral blood mononuclear cells

RA:

Rheumatoid arthritis

RF:

Rheumatoid factor

TNF:

Tumor necrosis factor

Treg:

Regulatory T cell

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Acknowledgments

The study was supported by the Hungarian Scientific Research Fund (OTKA) (grant no. 101661), Social Renewal Operational Programme (grant no. TÁMOP-4.2.2.-08/1/KMR-2008-0004), and research grants from Abbott Laboratories and Pfizer. Attila Balog was supported by the Zoltán Magyary Scholarship (grant no. TÁMOP-4.2.4. A/2-11-1-2012-001). László Kovács was supported by the Bolyai János Scholarship from the Hungarian Academy of Sciences.

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Authors and Affiliations

  1. Department of Laboratory Medicine, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4, 14th floor, 1089, Budapest, Hungary

    Balázs Szalay & Barna Vásárhelyi

  2. First Department of Pediatrics, Faculty of Medicine, Semmelweis University, Budapest, Bókay J. u. 53-54, 1083, Budapest, Hungary

    Áron Cseh & Tivadar Tulassay

  3. Research Laboratory for Pediatrics and Nephrology, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary

    Tivadar Tulassay

  4. Department of Rheumatology, Faculty of Medicine, Albert Szent-Györgyi Health Center, University of Szeged, Kálvária sgt. 57., 6725, Szeged, Hungary

    Magdolna Deák, László Kovács & Attila Balog

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  1. Balázs Szalay
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  2. Barna Vásárhelyi
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  7. Attila Balog
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Correspondence to Balázs Szalay.

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Szalay, B., Vásárhelyi, B., Cseh, Á. et al. The impact of conventional DMARD and biological therapies on CD4+ cell subsets in rheumatoid arthritis: a follow-up study. Clin Rheumatol 33, 175–185 (2014). https://doi.org/10.1007/s10067-013-2352-x

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  • DOI: https://doi.org/10.1007/s10067-013-2352-x

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