Highlights
- •The serum LDH level correlates with the clinical improvement and are downregulated by apremilast in psoriasis.
- •The serum LDH level reflects the oxygen consumption rate of blood T cells in the psoriatic patients.
- •Our results imply that the metabolic skew in immune cells could be a treatment target in psoriasis.
Abstract
Background
The efficacy of small molecule inhibitors for intracellular signal mediators varies
among the individuals, and their mechanism of action is broad. A phosphodiesterase
4 inhibitor apremilast shows a dramatic effect on a certain proportion of psoriatic
patients by modulating the cellular metabolism and regulating the production of pro-inflammatory
molecules. However, it is unclear to which disease subtype this drug benefits. While
psoriasis is a Th17-mediated disease, how immune cells are affected by the modulation
of cellular metabolism is not fully evaluated, either.
Objective
This study aims to identify the indices which predict the efficacy of apremilast in
psoriasis, and to investigate the impact of metabolic activity in immune cells on
the psoriatic pathogenesis.
Methods
The association of treatment efficacy with clinical and laboratory data of the 58
psoriatic patients was evaluated. The reflector of the associated index was also sought
among the indices of cellular metabolic pathways by use of an extracellular flux analyzer.
Results
There was a correlation between clinical improvement and the serum lactate dehydrogenase
(LDH) level in the patients treated with apremilast but not in those with biologics.
Serum LDH level did not correlate with the cutaneous disease severity but correlated
with the oxygen consumption rate of blood T cells.
Conclusion
Psoriatic patients with high serum LDH level can be benefitted by apremilast. The
serum LDH level reflects the augmented respiratory activity of T cells in psoriasis.
Our results would highlight the importance of regarding metabolic skew in immune cells
as a treatment target in psoriasis.
Abbreviations:
ATP (adenosine triphosphate), cAMP (cyclic adenosine monophosphate), ECAR (extracellular acidification rate), IL (interleukin), LDH (lactate dehydrogenase), OCR (oxygen consumption rate), OXPHOS (oxidative phosphorylation), PASI (psoriasis area and severity index), PDE4 (phosphodiesterase 4), Th (T helper lymphocytes)Keywords
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Article info
Publication history
Published online: July 21, 2021
Accepted:
July 19,
2021
Received in revised form:
July 15,
2021
Received:
May 27,
2021
Identification
Copyright
© 2021 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
