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Critical Reviews™ in Immunology
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ISSN Online: 2162-6472

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Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.2020033243
pages 361-377

Pathogenesis of Psoriatic Arthritis

Francesco Caso
Rheumatology Unit, Department of Clinical Medicine and Surgery, School of Medicine, University Federico II of Naples, Via S. Pansini 5, 80131, Naples, Italy
Luisa Costa
Rheumatology Unit, Department of Clinical Medicine and Surgery, School of Medicine, University Federico II of Naples, Via S. Pansini 5, 80131, Naples, Italy
Maria Sole Chimenti
Rheumatology, Allergology and Clinical Immunology, University of Rome Tor Vergata, Rome, Italy
Luca Navarini
Unit of Allergology, Clinical Immunology and Rheumatology, Università Campus Bio-Medico di Roma, Rome, Italy
Leonardo Punzi
Department of Clinical Medicine DIMED, University of Padova, Padua, Italy; Centre for Gout and Metabolic Bone and Joint Diseases, Rheumatology, SS Giovanni and Paolo, Venice, Italy


Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy involving synovial and entheseal structures, associated with psoriasis or similar conditions. The etiopathogenetic mechanisms underlying PsA remain unclarified. The most accredited hypothesis involves a complex interaction among genetic, environmental, and immunological factors. Environmental agents, particularly trauma, mechanical stress, and smoke have been cited as possible factors in triggering the disease in genetically predisposed subjects. Like other forms of spondyloarthropathies, PsA shows several genetic associations with the major histocompatibility complex (MHC) class I alleles located on chromosome 6p21.3, particularly the human leukocyte antigen (HLA)-B27 in axial phenotypes. Recent studies have demonstrated that the most common epigenetic mechanisms that regulate gene expression in PsA are represented by DNA methylation, parent of origin effect or genomic imprinting, expression or activity of epigenetic modifying enzymes, and RNA interference (RNAi) by microRNAs (miRNAs). The mechanisms underlying PsA pathogenesis activate the innate and adaptive immune system and overexpression of TNF associated with amplification of the IL-23/IL-17 axis. In recent years, more PsA susceptibility genes and epigenetic mechanisms have been identified. Advances in the knowledge of innate and adaptive immune mechanisms underlying PsA have contributed to a better understanding of the heterogeneous clinical expression of the disease and, thus, to therapy strategies. The complexity of the pathogenetic aspects involving multiple cytokines, cell lines, and molecules needs to be further investigated to advance personalized therapeutic strategies and to improve outcomes of patients affected by PsA.


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