Immunomodulation in psoriatic arthritis: focus on cellular and molecular pathways.

Maria Sole Chimenti, Eleonora Ballanti, Carlo Perricone, Paola Cipriani, Roberto Giacomelli, Roberto Perricone

Rheumatology, Allergology and Clinical Immunology, Department of Internal Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy.

Autoimmunity reviews 2013 Mar

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Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis. Pathogenesis is incompletely understood and pathophysiological role of synovium is just beginning to be elucidated. PsA could be considered an enthesal disease and this hypothesis is the link between mechanical stress (entheses) and immunologically active tissue (synovium). Histologically, PsA is characterized by lining layer hyperplasia, diffuse infiltrate of B, T, macrophages and dendritic cells associated with neutrophils' proliferation and angiogenesis. T cells are present, and oligoclonal T-cell expansions have been demonstrated in both skin and synovium. Histological findings are associated with monocyte-derived cytokines expression, as Myeloid-related protein (S100A8/A9). They play an important role in intracellular functions and cytoskeleton-membrane interactions. S100A8/A9 has a role in the propagation and perpetuation of the inflammatory process in patients with psoriasis and PsA, because of an activated monocyte/macrophage system that involve, distal to the skin, the "enthesal-complex." Complement system can be considered part of the acute phase response as demonstrated by higher plasma levels of C3 and C4 complement components in PsA patients compared with healthy subjects. These abnormal levels are then reverted by anti-TNF drugs. Evidences of efficacy of anti-TNF are expressed by reduction of vascularity and immune cells in synovial tissue. Therefore, innate response generates high concentrations of inflammatory cytokines which promote effector functions of a variety of tissue cells and sustain the characteristic chronicity of synovitis. The challenge will be the development of molecules affecting the balance between innate and adaptive immunity without affecting beneficial functions of the perfect concert of immunological process. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Citation

Maria Sole Chimenti, Eleonora Ballanti, Carlo Perricone, Paola Cipriani, Roberto Giacomelli, Roberto Perricone. Immunomodulation in psoriatic arthritis: focus on cellular and molecular pathways. Autoimmunity reviews. 2013 Mar;12(5):599-606