Spondilite anchilosante ed un nuovo allele HLA-B27 non associato alla malattia. Implicazioni patogenetiche

The strong association between ankylosing spondylitis and HLA-B27 is known since about 25 years ago. Several attemps have been made to understand the basis of this association but the issue has remained to date an open challenge. The most favoured hypothesis is that HLA-B27 molecules can present to T lymphocytes an 'arthritogenic' peptide capable of inducing an aberrant immune response. Accordingly, a common goal is to define the nature of such peptide, through the elucidation of the specific peptide-binding properties of HLA-B27 molecules. There are several HLA-B27 subtypes which differ for few amino acids clustered around the peptide-binding groove and whose association to the disease is variable. The recent discovery by our group of a new non- AS associated allele (HLA-B*2709), which shows distinctive peptide-binding properties, is likely to allow a better definition of the features of the 'arthritogenic' peptide. Indeed, HLA-B*2709 does not bind peptides with a Tyrosin at C-terminus that, instead, well fits into the peptide binding groove of the common, AS-associated, HLA-B*2705 subtype. This information will help in narrowing the number of candidate peptides and provides a unique tool for experimental approaches, towards the understanding of the disease pathogenesis.