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 High expression of antimicrobial peptide Beta Defensin 2 in bladders of women with IC compared to healthy controls.

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Join date : 2016-01-31

PostSubject: High expression of antimicrobial peptide Beta Defensin 2 in bladders of women with IC compared to healthy controls.   Fri Jun 17, 2016 1:29 am

I found this study I will post the summary below and a link to both the summary and the study its self. I hope this can be of help to Professor Marshall and his colleagues.

Our findings
We recruited 10 female volunteers with IC and compared with over 30 female volunteers with ‘normal’
bladders. Volunteers had biopsies taken from their bladder and vagina and collected an overnight urinecollection
and washings from the vagina. We also collected blood samples. We investigated for the presence
of several AMPs (Beta Defensin 1, Beta Defensin 2, Human alpha-Defensin 5 and Cathelicidin) in both
bladder biopsies and urine. Although, there were no significant findings in relation to three of the AMPs, we
found that in biopsies taken from IC patients, there were significantly higher levels of beta defensin 2 (BD2)
compared with normal and that biopsies obtained from areas of the bladder with Hunner’s ulcers exhibited the
highest levels of Beta defensin 2 . These results suggest that extra BD2 is released into the bladder during IC
and that the amount of BD2 seem to relate the extent of the bladder reaction. In urine samples, we found very
low levels of BD2 were detectable in the urine of healthy subjects but again these levels were significantly
increased in IC patients and were heading more towards the levels you would normally expect to see in
women with an active UTI. Taken together, these findings suggest that secretion of BD2 is significantly
increased in IC patients and that this response has similarities to that seen during UTI. This suggests that
despite the absence of bugs in IC, the bladder is still mounting an infection-type response leading to
continued unpleasant symptoms.
Interestingly BD2 also has an important role in activating some other cells in the immune system including
mast cells. The presence of large number of mast cells has long been recognised as key abnormal finding in
the bladder of patients with IC as have many of the products that mast cells produce. Indeed, mast cells are
reported to be activated in around 80% of patients with IC but no-one has been sure what their role is in the
normal bladder let alone one with IC. We therefore speculate that abnormally elevated levels of BD2 may play
a key role in activating this abnormal mast cell response.

Future work
Currently we still don’t know why people get IC but it is likely to involve genetic and environmental factors.
While urinary infection may not directly contribute to IC, a large number of IC patients report that their
symptoms are very similar episodes of cystitis caused by bladder bugs. It is also notable that UTIs, like IC, are
most frequent in women and that most IC patients have reported UTIs earlier in their lifetime, suggesting there
may well be an association between IC and a previous history of UTIs.
Recent studies carried out at Duke University, USA by the Abraham group have shown that mast cells play a
key role in mobilising bladder defences during and even following infection. They found that mast cells come
to the surface of the bladder and these cells persist for extended periods of time even after infection has
resolved. They found that in mice that had multiple infections, the mast cells started to persist in the bladder
and this was accompanied by changes to the bladder structure which allowed toxins in the urine to enter the
bladder wall. The findings generated by our COB Foundation funded study, has attracted the interest of the
American Research Group and we have recently submitted a collaborative research proposal with Professor
Abraham to the American National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to
further examine the role of BD2 and mast cells over a longer time course in patients with IC and correlate
these with patients symptoms and their findings in mice

Summary link: http://www.cobfoundation.org/UserFiles/File/Newcastle%20Research%20Up-date%20Document.pdf
Study Link: http://www.ics.org/Abstracts/Publish/180/000051.pdf
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