Hi Jake,
If you thought that was double dutch, cop this one, the association of AS with CMP2
Capillary Morphogenesis Protein 2 (CMP2) Chromsome 4q 21.21
CMP2 (also known as ANTXR2, Anthrax Toxin Receptor 2) is widely expressed in human tissue, indicating that this receptor is likely to be relevant for disease pathogenesis. It should be noted that for both axial and peripheral disease sites in SpA inflammation develops in close proximity to cartilage or fibro-cartilage enthesis and there is a very pronounced neo-vascularisation in all inflamed tissue.
Although the precise function of CMP2 is not yet known, it’s extracellular VWA/I domain (von Willebrand Factor type A domain also known as Integrin inserted domain) binds collagen type IV and laminin, suggesting that these are its natural ligands in vivo and that it may be involved in extracellular matrix adhesion.
There are three isoforms of CMP2. Isoform 1 is expressed on cell surfaces; isoform 2 is expressed predominantly within the endoplasmic reticulum, and isoform 3 is secreted.
ANTXR2 (CMP2) is sufficiently similar to ANTXR1 (ATR/TEM8) to function as an anthrax toxin receptor. Other than this similarity the two receptors are encoded by genes on two different chromosomes and their apparent functions in vivo are probably unrelated.
It is thought that CMP2 functions to promote endothelial (cells that line the blood vessels) proliferation and morphogenesis (beginning of the shaping of new capillaries) during sprouting angiogenesis (formation of new blood vessels), consistent with expression of CMP2 in several vascular beds. CMP2 may have a possible role in endothelial (and epithelial) basement membrane (the thin sheet of fibres that underlie the endothelium or epithelium) matrix synthesis and assembly.
It is well known that vascular endothelial growth factor (VEGF) is increased in active AS (as is IL-6). Also IL-23 is known to promote angiogenesis. In RA (and presumably in AS) VEGF is released in response to raised TNFa increasing endothelial permeability and swelling and stimulating angiogenesis (formation of new capillaries).
Note that recessive mutations of CMP2 (that is 2 non functioning genes) causes juvenile hyaline fibromatosis and infantile systemic hyalinosis, conditions characterised by multiple skin nodules and hyaline deposition (at or near the basement membrane?), osteolytic bone lesions, and joint contractures. In infantile systemic hyalinosis (at least) gastrointestinal dysfunction (diarrhoea) is a major symptom.
Cheers David
