Jonathan Edwards
"Gibberish"
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The ligament inflammation seems to be due to T or NK cells getting activated there for no good reason. Nobody fully understands why ligaments are a good place for T cells to play but there is a likely story.
In all of the T cell related 'seronegative spondarthropathies' we see inflammation in the chosen T cell zone (1. mucosa, 2. skin, 3. gut) PLUS inflammation at ligament attachments and nail beds. Nail beds are attached to bone so are pretty similar to ligament attachments. But in the disease of the number 4. zone ('everywhere else') we also see inflammation at a very curious group of sites:
Ligament insertion again - but widespread up and down the spine and sacroiliac joints (alias 'ankylosing spondylitis')
Nail bed again
Aortic root
Iris attachment in the eye
Apex of lung
Caudal spinal root sheaths
These might seem all very different but many people have noted that they are all sites of tension where elastin is important. And there is a disease of elastic fibres that affects exactly the same places - called Marfan syndrome. So the idea is that what we looking at is T cells playing out at sites of high tensile stress. The possible link is that wherever there is tensile stress fibroblasts will secrete TGFbeta. This is an anti-inflammatory cytokine and it may be needed to prevent inflammation from dissolving the tissue and causing it to pull apart. However, TGFbeta also regulates the expression of HLA-B on cells and the clue to all these diseases is a link to HLA-B27. The suggestion is that under certain circumstances TGFbeta has a paradoxical inflammatory, or perhaps 'scarring' reaction effect by allowing T cell interactions that would normally be switched off by interactions with HLA-B. This would make sense for NK cell interactions but nobody knows exactly what is going wrong.
Ligament insertion inflammation (or 'enthesitis') can be helped symptomatically by anti-inflammatories like ibuprofen or diclofenac. But a much more powerful effect is seen with TNF inhibitors, which will often abolish symptoms completely. The down side of TNF inhibition is susceptibility to infection. This is not a problem in most cases but is serious for a few. So TNF inhibitors are only used if there is a very good justification.
In all of the T cell related 'seronegative spondarthropathies' we see inflammation in the chosen T cell zone (1. mucosa, 2. skin, 3. gut) PLUS inflammation at ligament attachments and nail beds. Nail beds are attached to bone so are pretty similar to ligament attachments. But in the disease of the number 4. zone ('everywhere else') we also see inflammation at a very curious group of sites:
Ligament insertion again - but widespread up and down the spine and sacroiliac joints (alias 'ankylosing spondylitis')
Nail bed again
Aortic root
Iris attachment in the eye
Apex of lung
Caudal spinal root sheaths
These might seem all very different but many people have noted that they are all sites of tension where elastin is important. And there is a disease of elastic fibres that affects exactly the same places - called Marfan syndrome. So the idea is that what we looking at is T cells playing out at sites of high tensile stress. The possible link is that wherever there is tensile stress fibroblasts will secrete TGFbeta. This is an anti-inflammatory cytokine and it may be needed to prevent inflammation from dissolving the tissue and causing it to pull apart. However, TGFbeta also regulates the expression of HLA-B on cells and the clue to all these diseases is a link to HLA-B27. The suggestion is that under certain circumstances TGFbeta has a paradoxical inflammatory, or perhaps 'scarring' reaction effect by allowing T cell interactions that would normally be switched off by interactions with HLA-B. This would make sense for NK cell interactions but nobody knows exactly what is going wrong.
Ligament insertion inflammation (or 'enthesitis') can be helped symptomatically by anti-inflammatories like ibuprofen or diclofenac. But a much more powerful effect is seen with TNF inhibitors, which will often abolish symptoms completely. The down side of TNF inhibition is susceptibility to infection. This is not a problem in most cases but is serious for a few. So TNF inhibitors are only used if there is a very good justification.