title: Glutathione peroxidase activity in the blood cells of psoriatic patients correlates with their responsiveness to Efalizumab.
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.
authors.affiliation: Tissue Engineering & Skin Pathophysiology Laboratory, Dermatology Research Institute (IDI IRCCS), Rome 00167, Italy.
authors.forename: Saveria
authors.initials: S
authors.lastname: Pastore
authors.forename: Valentina
authors.initials: V
authors.lastname: Mariani
authors.forename: Daniela
authors.initials: D
authors.lastname: Lulli
authors.forename: Emanuela
authors.initials: E
authors.lastname: Gubinelli
authors.forename: Desanka
authors.initials: D
authors.lastname: Raskovic
authors.forename: Serena
authors.initials: S
authors.lastname: Mariani
authors.forename: Andrea
authors.initials: A
authors.lastname: Stancato
authors.forename: Chiara
authors.initials: C
authors.lastname: de Luca
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pecorelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valacchi
authors.forename: Alla I
authors.initials: AI
authors.lastname: Potapovich
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Kostyuk
authors.forename: Liudmila G
authors.initials: LG
authors.lastname: Korkina
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D001773:Blood Cells / Q000166:cytology / Q000201:enzymology*; D002374:Catalase / Q000097:blood / Q000187:drug effects; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D005231:Fatty Acids, Unsaturated / Q000097:blood / Q000378:metabolism*; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood* / Q000187:drug effects*; D005982:Glutathione Transferase / Q000097:blood / Q000187:drug effects; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology; D011565:Psoriasis / Q000097:blood* / Q000188:drug therapy*; D012074:Remission Induction; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D005231:Fatty Acids, Unsaturated; D008315:Malondialdehyde; D002374:Catalase; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; C472181:efalizumab