Hi Chris
Hope this helps
HLA-B27 Human Leukocyte Antigen B27
Located on Chromosome 6
HLA-B27 is one of 60 or so HLA-B alleles, and is a Major Histocompatibility Complex (MHC) Class I gene that encodes a peptide binding protein (in this case HLA-B27) that are expressed on all nucleated cells. The molecules consist of an alpha chain and B2microglobulin (not part of MHC) and present ligands (antigen fragments of 8-10 amino acids long, usually virally derived or ‘self’, but also can be derived from intracellular bacteria) to T-cells via CD8 receptors on cytotoxic T-cells (CTL or Tc) and also bind inhibitory receptors on Natural Killers cells.
ERAP1 Endoplasmic Reticulum Amino Peptidase 1
Located on Chromosome 5q15
The association of ERAP1 and disease is a major breakthrough in AS research.
The gene product has two known functions, either of which could explain its disease association. Within the Endoplasmic Reticulum of a cell, ERAP1 is responsible for trimming peptides to optimal length for MHC Class I presentation. Since AS is primarily an MHC Class I mediated disease, this has implications favouring mechanisms of disease generation that involve abnormalities of peptide presentation above those involving abnormal forms of B27 molecules (such as the Unfolded Protein Response (UPR)). However, the second known function of ERAP1 is that it cleaves cell surface receptors for the pro-inflammatory cytokines IL-1 (IL1R2), IL-6 (IL6Ra), TNFa (TNFRSF1A) and IL-23 (IL-23R), thereby down regulating the signalling potential of IL-1, IL-6, TNFa and IL-23 to promote inflammation. ‘Loss of function’ of ERAP1 inherited variants could thus have pro-inflammatory effects through this mechanism, that is, if you inherit an ERAP1 allele that is AS-associated it may be less functional than the other ERAP alleles.
