Abstract
Psoriasis and psoriatic arthritis are multifactorial chronic disorders whose etiopathogenesis essentially derives from the alteration of several signalling pathways and the co‐occurrence of genetic, epigenetic and non‐genetic susceptibility factors that altogether affect the functional and structural property of the skin. Although shared and differential susceptibility genes and molecular pathways are known to contribute to the onset of pathological phenotypes, further research is needed to dissect the molecular causes of psoriatic disease and its progression towards Psoriatic Arthritis. This review will therefore be addressed to explore differences and similarities in the etiopathogenesis and progression of both disorders, with a particular focus on genes involved in the maintenance of the skin structure and integrity (keratins and collagens), modulation of patterns of recognition (through Toll‐like receptors and dectin‐1) and immuno‐inflammatory response (by NLRP3‐dependent inflammasome) to microbial pathogens. In addition, special emphasis will be given to the contribution of epigenetic elements (methylation pattern, non‐coding RNAs, chromatin modifiers and 3D genome organization) to the etiopathogenesis and progression of psoriasis and psoriatic arthritis. The evidence discussed in this review highlights how the knowledge of patients' clinical and (epi)genomic make‐up could be helpful for improving the available therapeutic strategies for psoriasis and psoriatic arthritis treatment.
Highlights
The effectiveness of skin as protective organ is provided by a peculiar structure designed to counteract a variety of dangerous events, including mechanical stress, transepidermal water loss, penetration of microorganisms or physico-chemical irritants
The expression of COL6A5 in the papillary dermis[42] suggested a potential association with Ps and psoriatic arthritis (PsA), given the fact that the papillary dermis can be affected in both disorders. Supporting this hypothesis, we found a significant association of rs12488457 (A/C) variant located in COL6A5 with Ps and PsA in a recent study on the Italian population.[48]
We found that the COL10A1-rs3812111 (T/A) variant was exclusively associated with PsA, suggesting the possible contribution of bone metabolism-related factors in the differential etiopathogenesis of PsA compared to Ps.[48]
Summary
The effectiveness of skin as protective organ is provided by a peculiar structure designed to counteract a variety of dangerous events, including mechanical stress, transepidermal water loss, penetration of microorganisms or physico-chemical irritants. TA B L E 1 Overview of the genes potentially contributing to the etiopathogenesis of Psoriasis and Psoriatic Arthritis discussed throughout the manuscript
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