Human Leukocyte Antigen (HLA) part 117

hla protein 1

 

Ankylosing spondylitis  is a complex disease involving multiple risk factors, both genetic and environtmental. Ankylosing spondylitis patients are predominantly  young men, and the disease is characterized by inflammation  and ankylosis, mainly at the cartilage bone interface and enthesis. HLA-B27 has been known to be the major ankylosing spondylitis susceptibility gene for more than 40 years and is present in over 90% of ankylosing patients. There are about HLA-B*2731 alleles with the B*2701,B*2704 and *2705 alleles are strongly associated with susceptibility, and B*2706 and B*2709 alleles are associated with protection. The presence of amino acid Aspartate or Histidine at position 116 is the only difference between B*2705 and B*2709. There are three principle to distinguish it from other HLA class I molecules such as  the peptide-binding specifity, the tendency to misfold and the predilection  for forming heavy chain homodimers during cell-surface recycling. The current hypotheses linking HLA-B27 to spondyloarthritis pathogenesis includes:

  • Arthritogenic peptides, self peptide selected and presented by properly folded forms of HLA-B27 complexed with β2 m have been  hypothethesized to be the target of autoreactive CD8 T cells and serve as an upstream initiator of inflammation
  • Recognitizion of non-canonical HLA-B27, naturally occuring self-surface HLA-B27 dimers are hypothesized  to be recognized by killer immunoglobulin receptors (such as KIR3DL2) in the leucocyte immunoglobulin like receptor family and trigger inflammation
  • HLA-B27 misfolding, the formation of misfolded oligomers and BiP binding by newly synthesized HLA-B27 heavy chains causes ER stress, which has intrinsic effects on cellular function that are hypothesized to promote development of spondyloarthritis.

HLA-B27 can exhibit all three of these behaviours in the same cell and these concepts are not mutually exclusive.

Advertisements

About azaleaazelia

A nice person... :)
This entry was posted in Tak Berkategori. Bookmark the permalink.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s