Glutathione peroxidase activity in the blood cells of psoriatic patients correlates with their responsiveness to Efalizumab

Saveria Pastore, Valentina Mariani, Daniela Lulli, Emanuela Gubinelli, Desanka Raskovic, Serena Mariani, Andrea Stancato, Chiara De Luca, Alessandra Pecorelli, Giuseppe Valacchi, Alla I. Potapovich, Vladimir A. Kostyuk, Liudmila G. Korkina

Research output: Contribution to journalArticle

Abstract

Biological treatment of psoriasis, a chronic inflammatory immune-mediated pathology of huge social impact, has become a recent revolutionizing breakthrough in the management of the disease. Apart from anti-TNF-alpha biologics, recombinant proteins-inhibitors of the T lymphocytes-antigen presenting cells interaction, Efalizumab among them, have been successfully used in the therapy of psoriasis. Serious concern regarding safety and efficacy of biologics remains because they induce numerous adverse effects and a significant number of patients are non-responders. Up-to-now, there are no biochemical or/and immunological markers of the clinical efficacy of these drugs. This study searches for immunological and redox markers of the clinical response in the group of psoriatic patients treated with Efalizumab. Clinical response to Efalizumab was assessed by Psoriasis Area and Severity Index and correlated with suppression of T-cell functions, plasma cytokines, membrane-associated polyunsaturated fatty acids (PUFAs), antioxidant enzymes and markers of oxidative stress. A 12-week Efalizumab therapy did not affect abnormal plasma levels of pro-inflammatory cytokines and lower-than-normal content of PUFAs esterified in phospholipids of red cell membranes. It did, however, suppress T-cell-mediated functions and decrease nitrites/nitrates and malonyl dialdehyde levels independently on the clinical outcome. On contrast, activities of glutathione peroxidase (GPx) and glutathione S-transferase in granulocytes were remarkably increased and catalase decreased exclusively in non-responders vs complete or partial responders. High baseline GPx in erythrocytes decreased in responders. It is concluded that clinical response to Efalizumab correlates with GPx activity in the blood cells, suggesting that high hydroperoxide levels are involved in psoriasis persistence.

Original languageEnglish
Pages (from-to)585-599
Number of pages15
JournalFree Radical Research
Volume45
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • Catalase
  • cytokines
  • Efalizumab
  • glutathione peroxidase
  • glutathione-S- transferase
  • MDA
  • psoriasis
  • PUFAs

ASJC Scopus subject areas

  • Biochemistry

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  • Cite this

    Pastore, S., Mariani, V., Lulli, D., Gubinelli, E., Raskovic, D., Mariani, S., Stancato, A., De Luca, C., Pecorelli, A., Valacchi, G., Potapovich, A. I., Kostyuk, V. A., & Korkina, L. G. (2011). Glutathione peroxidase activity in the blood cells of psoriatic patients correlates with their responsiveness to Efalizumab. Free Radical Research, 45(5), 585-599. https://doi.org/10.3109/10715762.2011.560150