Different Effects of Tumor Necrosis Factor and IL-17A Blockades on T
Cell Function of Psoriatic Arthritis Patients
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.