[Psoriatic arthritis as MHC-I-associated disease]

Psoriatic arthritis is a heterogeneous, immune-mediated systemic disease with manifestations affecting joints, entheses and skin. A characteristic feature is the absence of autoantibodies, while mechanisms of innate and tissue-resident immunity predominate. The concept of MHC-I-associated diseases provides an integrative framework for pathogenetic classification. Central elements of the concept include the association with HLA class I alleles, alterations in antigen processing, for example mediated by ERAP1/2, and activation of the interleukin IL-23/IL-17 axis. The enthesis functions as a key organ in which mechanical stress, microbial stimuli and genetic predisposition trigger local immune activation. This leads to the development of a systemic inflammatory response involving different clinical domains. Genetic and immunological heterogeneity explain the diversity of phenotypes and treatment responses and underpins the perspective of endotype-based stratification for precision medicine approaches.