IN THIS ISSUE ... see article on pp 782
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ActaDV ActaDV
Advances in dermatology and venereology Acta Dermato-Venereologica
The AGEs of Psoriasis : A Biomarker for Severity and a Pathogenetic Link to Comorbidities
Advanced glycation end products ( AGEs ) are highly oxidant compounds derived from non-enzymatic glycosylation reactions of reducing sugars with proteins , lipids or nucleic acids , which become structurally modified with altered functionality ( 1 ). Exogenous sources of AGEs include cigarette smoke and components of the diet . AGEs can be ingested with high temperature processed foods and formed as a consequence of high dietary sugar intake . In fact , dietary-induced AGEs have been demonstrated to interfere with many cell functions , contributing to the onset of organ damage in liver ( 2 ) AGEs accumulate continuously in human tissues during the entire lifespan and have been involved in the pathogenesis of age-related diseases , such as neurodegenerative diseases , atherosclerosis , diabetes , chronic inflammatory diseases , cancer and human skin ageing ( 1 ). AGEs have been associated with arterial stiffness in patients with hypertension and are important enhancers of diabetes complications ( 3 , 4 ).
AGEs exert their biological actions through binding to a pattern recognition cell surface receptor , RAGE , and triggering several signalling pathways involved in inflammation and tumorigenesis . RAGE is expressed in many cell types , including lymphocytes , macrophages , endothelial cells and keratinocytes , and binds other ligands , such as S100 proteins and high-mobility group box 1 ( HMGB1 ) that have been involved in the pathogenesis of psoriasis . The 2184G allele of a RAGE gene polymorphisms has been associated with psoriasis in patients with a negative history of cardiovascular diseases or diabetes ( 5 ), and serum concentrations of AGEs have been found to be elevated in patients with active psoriasis in comparison to healthy individuals , and to return to the normal range in the remission phase ( 6 ). This study did not take into account patients ’ comorbidities , and the serum levels of AGEs were not found to correlate with the Psoriasis Area and Severity Index ( PASI ).
The present issue of ActaDV includes an excellent study and review by Papagrigoraki et al . ( 7 ), who conclude that patients with severe psoriasis have accumulation of AGEs in the skin and serum , independent of associated metabolic disorders . They included in their study 40 patients with mild psoriasis ( median PASI 4.5 ), 40 patients with severe psoriasis ( median PASI 16.2 ), 40 patients with severe chronic eczema and 40 healthy individuals . Patients and healthy individuals with psoriatic arthritis , smoking habit , diabetes , dyslipidemia , hypercholesterolemia , hypertension , systemic inflammatory , metabolic or autoimmune disease or are under systemic treatment or phototherapy were excluded , and there were no differences in age , sex , body mass index , plasma cholesterol , triglycerides , creatinine , liver enzymes and glucose levels between cases and controls . Serum levels of AGEs correlated well with skin levels and , most interestingly , with psoriasis severity ( PASI ). In addition , serum levels of soluble RAGE were found to correlate inversely with disease severity in patients with psoriasis .
AGEs are usually measured using skin fluorescence and enzyme-linked immunoassays in serum or plasma , but in most reports both techniques are used separately . The correlation of skin and serum measurements with psoriasis severity suggests that skin fluorescence can be a simple and useful method to study the effect of treatment and comorbidities on AGEs in patients with psoriasis , or to identify those patients with a higher oxidative burden and potential risk to develop cardiovascular or metabolic comorbidities of psoriasis .
Future studies should provide further information on the importance of the smoking habit or diet on the overall levels of AGEs in psoriasis . Obesity is common in psoriasis patients , and one can speculate that the dietary intake of sugars in obese patients is greater than in the normal weight population , even in the absence of diabetes or insulin resistance . If this was the case , the relative contribution of diet to the measured levels of AGEs would be of great interest . As regards diabetes , one of the challenges to prevent the development of complications is to reduce not only the glycaemia levels but also the levels of dietary AGEs . The same strategy applied to patients with severe psoriasis might contribute to control the inflammation and severity of disease , at least in difficult-to-treat patients , and help to prevent cardiovascular and metabolic complications , in patients with severe psoriasis .
Furthermore , AGEs might prove to be a useful biomarker of both systemic and cutaneous inflammation in psoriasis , and therapeutic interventions on the AGE / RAGE pathways might prove to open new perspectives for improved control of both psoriasis and its comorbidities .
REFERENCES
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2 . Aragno M , Mastrocola R . Dietary sugars and endogenous formation of advanced glycation endproducts : emerging mechanisms of disease . Nutrients 2017 ; 9 : pii : E385 .
3 . Yamagishi S , Matsui T . Pathologic role of dietary advanced glycation end products in cardiometabolic disorders , and therapeutic intervention . Nutrition 2016 ; 32 : 157 – 165 .
4 . Prasad K , Mishra M . Do advanced glycation end products and its receptor play a role in pathophysiology of hypertension ? Int J Angiol 2017 ; 26 : 1 – 11 .
5 . Vasků V , Kanková K , Vasků A , Muzík J , Izakovicová Hollá L , Semrádová V , et al . Gene polymorphisms ( G82S , 1704G / T , 2184A / G and 2245G / A ) of the receptor of advanced glycation end products ( RAGE ) in plaque psoriasis . Arch Dermatol Res 2002 ; 294 : 127 – 130 .
6 . Damasiewicz-Bodzek A , Wielkoszyński T . Advanced protein glycation in psoriasis . J Eur Acad Dermatol Venereol 2012 ; 26 : 172 – 179 .
7 . Papagrigoraki A , Del Giglio M , Cosma C , Maurelli M , Girolomoni G , Lapolla A . Advanced glycation end products are increased in the skin and blood of patients with severe psoriasis . Acta Derm Venereol 2017 ; 97 : 782 – 788 .
Lluís Puig and Anna López-Ferrer Department of Dermatology , Hospital de la Santa Creu i Sant Pau ,
Autonomous University of Barcelona , Barcelona , Spain . E-mail : LPuig @ santpau . cat
This is an open access article under the CC BY-NC license . www . medicaljournals . se / acta Journal Compilation © 2017 Acta Dermato-Venereologica . doi : 10.2340 / 00015555-2716 Acta Derm Venereol 2017 ; 97 : 775