Advanced glycation end products (AGEs) in patients with chronic plaque psoriasis

La formazione dei prodotti terminali della glicazione delle proteine (AGEs) è aumentata in condizioni caratterizzate da iperglicemia, iperlipidemia e stress ossidativo, un profilo metabolico frequentemente riscontrato in pazienti affetti da psoriasi cronica in placche.È stato effettuato uno studio trasversale caso-controllo, in ambiente ospedaliero, che ha valutato l’accumulo cutaneo ed ematico degli AGEs, comprendente i livelli totali degli AGEs, di pentosidina, del recettore di superficie cellulare per gli AGEs (RAGE) e del recettore solubile (sRAGE) in pazienti affetti da psoriasi lieve, psoriasi grave, eczema grave e in individui sani.Lo studio ha dimostrato un aumento statisticamente significativo degli AGEs nei pazienti affetti da psoriasi e una correlazione diretta tra gravità della patologia e valore degli AGEs. L’incremento dei livelli cutanei degli AGEs è risultato, inoltre, direttamente correlato a quello dei livelli sierici in tutti i soggetti partecipanti.I risultati suggeriscono che la glicazione proteica avanzata abbia un ruolo rilevante nella patogenesi della psoriasi e che possa portare a un aumentato rischio di sviluppare disturbi metabolici ed eventi cardiovascolari in pazienti con psoriasi.

Background: Psoriasis is a common chronic inflammatory immune mediated skin disease frequently associated with metabolic comorbidities. Advanced Glycation End Products (AGEs) are a group of highly oxidant, biological active compounds which tissue accumulation provokes structural alterations occurring mostly in conditions such as hyperglycemia, hyperlipedemia and oxidative stress, a metabolic profile frequently encountered in patients affected by psoriasis.Objectives: Investigate if psoriasis is associated with skin and serum AGEs accumulation, and evaluate the possible pathogenetic role of AGEs in linking psoriasis with metabolic disorders.Methods: This was a hospital-based cross-sectional case-control study including 80 patients with severe or mild psoriasis and 80 age, sex and body mass index matched controls (40 patients with severe eczema and 40 healthy individuals). Exclusion criteria were psoriatic arthritis, diabetes, dyslipidemia, hypercholesterolemia, hypertension, smoking habit or on-going treatment. Skin AGEs were measured in normal appearing skin of the forearm by a standard fluorescence technique. Blood AGEs levels, including total AGEs rate, total pentosidine, AGEs cellular receptor (RAGE) and soluble receptor (sRAGE) were measured by ELISA. Results: Cutaneous AGEs (P < .04), serum AGEs (P < .01) and pentosidine levels (P < .0001) were higher in patients with severe psoriasis compared to patients with mild psoriasis or severe eczema and healthy controls. Skin and serum AGEs levels well correlated in all subjects (r = 0.93, P < .0001). Cutaneous and serum AGEs highly correlated with the psoriasis area and severity score (r = 0.91, P < .0001). On the contrary, RAGE levels were lower (P < .001) in patients with severe psoriasis and inverse correlated with disease severity (r = -81, P < .0002). The sRAGE levels were significantly higher in patients with severe or mild psoriasis and in patients with severe eczema as compared to healthy individuals (P = .04, P = .007, P = .02 respectively).Conclusions: Patients with severe psoriasis have skin and serum accumulation of AGEs, independently from metabolic disorders. AGEs may be relevant to several aspects of psoriasis pathogenesis.