Ricerc@Sapienza

Ankylosing Spondylitis (AS) is a chronic inflammatory arthritis affecting primarily the spine and sacroiliac joints and belonging to Spondyloarthritis, a class of immune-mediated disorders. The AS strongest risk factor is the human leukocyte antigen class I gene, HLA-B*27. Recently, Endoplasmic Reticulum AminoPeptidases (ERAP) 1 and 2 genes have been identified by genome wide association studies as additional susceptibility factors. Some other autoimmune/autoinflammatory human diseases share a similar immunopathogenic ground. Accordingly, in all these polygenic disorders there is a principal risk factor which is a HLA class I gene: HLA-B*51 for Behçet's disease, HLA-A*2902 for Birdshot Chorioretinopathy and HLA-C*0602 for psoriasis, but a relevant role can also be attributed to ERAP1 and, in some cases, to ERAP2. Besides peculiar hallmarks imposed by different polygenic backgrounds, such disorders affect body sites undergoing physical stress at external barriers (oral mucosa, skin, gut, eye) or internal sites (joints, enthesis) implying a constant and multi-directional migration of pro-inflammatory cells of innate and adaptive immunity. The endogenous and/or exogenous aetiological triggers are usually unknown. Nevertheless, the co-occurring association of HLA class I and ERAP genes, involved in the peptide trimming, points at antigen processing and presentation pathway to CD8+ T cells as a putative pathogenic event.
A unifying concept proposes that aberrant innate immune reactions at mechanical stress sites or dysfunctions in environmental exposed organs could sustain secondary CD8+ T cell responses culminating in exacerbation and recurrence of such diseases. Thus, the aim of this project will be to study the migratory behaviour of CD8+ T cells in patients with AS by analysing: the chemokine receptor expression; the response to chemokine stimuli and the correlation with the immune-phenotype and senescence state evaluated by telomere shortening measurement.