Discovering the pathogenesis of autoimmune diseases at the 9th International Congress of Autoimmunity, Nice, France, 2014

Excerpt

It was probably a sign that the 9th International Congress on Autoimmunity was held in the astonishing setting of the Acropolis, Congress venue, in Nice. The word Acropolis comes from Greek from akros, “topmost,” and polis, “city”: It was indeed topmost the level of the contributions from the over 2000 scientists of the polis of the Autoimmunity Congress. The huge number of participants led to pulsating discussions on different aspects of autoimmunity. In this issue of Immunologic Research, are gathered papers referring to the novel findings on pathogenesis beginning from the genetic background. Reeves et al. [1] reviewed the role of the endoplasmic reticulum aminopeptidase 1 (ERAP1) in ankylosing spondylitis (AS). This zinc metallopeptidase has established roles in biological processes such as antigen processing for major histocompatibility complex (MHC) class I presentation, cytokine receptor shedding, angiogenesis/blood pressure regulation and activation of macrophage [2]. ERAP1 is interesting for its role in MHC I antigen-processing pathway where the generation of optimal antigens for loading onto MHC I molecules are essential for the stable expression of MHC I at the cell surface to circulating CD8⁺ T cells. The ERAP1 processing can foresee either the “molecular ruler” mechanism, in which ERAP1 trims the peptide precursor to the correct length for binding with the molecule itself acting as a length template, or a mechanism in which the MHC I acts as the template required by ERAP1. Nonetheless, ERAP1 is interesting also because in a way it can differentiate the pathogenesis of different autoimmune conditions. The genome-wide analysis studies have indeed found an association with a number of disorders sharing clinical and pathogenic features with AS: Behçet’s disease, psoriasis and psoriatic arthritis (PsA) [3]. These have in common uveitis, a (relatively) frequent axial involvement, and the interleukin IL-17/IL-23 pathway “signature.” Thus, it could be hypothesized that the combination of the HLA locus (B27 for AS and PsA, B51 for Behçet) plus the presence of other genetic variants, including ERAP1, may be responsible for different clinical onset. It is not surprising that we failed to find any association with systemic lupus erythematosus (SLE) [4]. In this disease, the role of IL-17 is better characterized, while that of IL-23 is less clear. Indeed, there is no association with IL-23 genetic variants and SLE [5]. This evidence may suggest that ERAP1 is quite associated with an IL-23 rather than an IL-17 milieu. …