The many faces of psoriatic arthritis: their genetic determinism

Abstract

In this review, we propose a model of PsA as a complex genetically determined autoimmune-mediated disease having a heterogeneous variety of subphenotypes, with each subphenotype under the control of a different susceptibility-associated HLA allele. Since the specific HLA molecules encoded by each susceptibility allele dominantly select a T cell repertoire with the property of recognizing different peptides, we hypothesize each subphenotype reflects a distinct adaptive autoimmune response directed to different target molecules that is mediated by T cells within each selected repertoire. The interaction among the patients' susceptibility alleles in the selection of their T cell repertoires determines a spectrum of overall clinical disease severity, varying from mild to severe. We further speculate that these different immune responses may result in activation of different immune effector pathways, which might therefore respond differently to various specific biologic agents.

Keywords: HLA allele; T cell repertoire; autoimmune response; clinical subphenotype; genotype.

Fig. 1

Hand radiograph from PsA patient demonstrating both new bone forming and resorptive features [12] Close up of plain radiograph of left hand from patient with PsA showing a destructive mutilating process affecting the interphalangeal joint of the left thumb that has resulted in subluxation. There is also evidence of new bone formation with periostitis along the shaft of the distal phalange of the thumb and ankylosis of the second distal interphalangeal joint.