Nailing down the Genetic and Immunological Basis for Psoriatic DiseaseMcGonagle D. · Palmou Fontana N. · Tan A.L. · Benjamin M.
aSection of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds and Chapel Allerton Hospital, Leeds, and bSchool of Biosciences, Cardiff University, Cardiff, UK; cRheumatology Department, Complejo Hospitalario Universitario A Coruña, La Coruña, Spain
Psoriatic disease encompassing skin, joint and nail involvement is largely viewed as autoimmune – a finding supported by data from animal models, the human leucocyte antigen (HLA)-Cw6 disease association in man, T-lymphocyte infiltration in lesional skin and the favourable skin response to T-cell-directed therapies. However, this immunopathogenetic model only applies to the skin, as recent studies failed to demonstrate a HLA-Cw6 association with the nails or joints. Furthermore, the nails and joints are intimately associated with inflammation at points of ligament or tendon insertion (i.e., enthesitis), so it is now appreciated that both of these sites also share a common microanatomical basis. Moreover, inflammation at insertion sites and nails does not appear to be associated with a particular antigenic territory but is quite diffuse in nature. This suggests that an aberrant response to tissue stressing of the integrated nail-joint apparatus, rather than autoimmunity, is driving the inflammatory process. Therefore, HLA-Cw6-associated type 1 psoriasis is more closely linked to autoimmunity, whereas nail and joint disease may be linked to tissue-specific factors, including tissue biomechanical stressing and microtrauma, that lead to activation of aberrant innate immune responses. These observations that stem from nail disease point toward a relative differential involvement of adaptive and innate immunity in the psoriatic disease spectrum and offer a fresh perspective on the pathophysiology of psoriatic disease and how it can be classified along the immunological disease continuum of self-directed inflammation.