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Different Effects of Tumor Necrosis Factor and IL-17A Blockades on T Cell Function of Psoriatic Arthritis Patients
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  • Smadar Gertel,
  • A Polachek,
  • Victoria Furer,
  • David Levartovsky,
  • Haya Sidis,
  • Sara Pel,
  • Daphna Paran,
  • Ori Elkayam
Smadar Gertel
Tel Aviv Sourasky Medical Center

Corresponding Author:[email protected]

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A Polachek
Tel Aviv Sourasky Medical Center
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Victoria Furer
Tel Aviv Sourasky Medical Center
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David Levartovsky
Tel Aviv Sourasky Medical Center
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Haya Sidis
Tel Aviv Sourasky Medical Center
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Sara Pel
Tel Aviv Sourasky Medical Center
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Daphna Paran
Tel Aviv Sourasky Medical Center
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Ori Elkayam
Tel Aviv Sourasky Medical Center
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Abstract

Biologics have revolutionized the treatment of inflammatory arthritis, but their impact on T cell function is unknown. We evaluated the effect of tumor necrosis factor-alpha (TNF-α), interleukin-17A (IL-17A), and IL-6 receptor (IL-6R) blockers on T cell function in psoriatic arthritis (PsA) patients. Peripheral blood mononuclear cells (PBMCs) from PsA patients (n=111) and healthy controls (n=20) were co-cultured with adalimumab (ADA), ixekizumab (IXE), tocilizumab (TCZ), or medium alone for 5 days. T cell activation and proliferation were determined by flow cytometry and cytokines in supernatants were measured by ELISA. Activated CD4+CD25+ T cells were significantly down-regulated by ADA in naïve, conventional disease-modifying anti-rheumatic drug (cDMARD)- and biologic-treated PsA patients compared to medium (p < 0.04, p < 0.01, respectively), IXE, and TCZ. In healthy, ADA reduced the activated CD4+CD25+ T cells proportion but non-significantly as compared to the other groups. Inhibition of PsA patients derived lymphocytes proliferation by the biologics was determined in response to phytohemagglutinin (PHA). The strongest ability to suppress the extent of PHA-induced proliferation was exerted by ADA (p < 0.01) compared to IXE and TCZ. IL-1β, IL-17A, and MMP-3 levels were down-regulated by ADA compared to medium (p < 0.02, p < 0.0001, p < 0.002, respectively). IXE reduced IL-17A (p < 0.0001) but not IL-1β or MMP-3 levels. TNF and IL-17A blockades are suitable for PsA treatment, but exhibit different activity on T cells. Moreover, the study reveals part of the mechanism exerted by ADA and provides a possible explanation for TCZ inefficacy in PsA.