Despite advances in treatment, peritoneal dialysis (PD)-associated peritonitis remains a major cause of morbidity and mortality in PD patients. Given that peritonitis can be the proximate cause of technique failure and cause ultrafiltration failure at a later time, it is important to understand the peritoneal immune response, microbiology and outcomes of these infections. Data presented in this thesis have shown that leukocytes are recruited to the peritoneal cavity, starting with a rapid accumulation of neutrophils, which are later replaced by a population of mononuclear cells, including monocytes/macrophages and T cells during acute peritonitis. Of note, Vγ9/Vδ2 T cells are also recruited to the peritoneal cavity in the early stage, which implies a significant role of Vγ9/Vδ2 T cells as early responders in acute peritonitis. In patients with acute peritonitis, the capacity of the causative pathogen to produce (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), together with the infiltration of activated Vγ9/Vδ2 T cells are important risk factors and possible predictors of patient outcomes from infection. By performing a detailed immunological and microbiological analysis in PD patients on the first day of peritonitis, our findings provide proof of concept that acute bacterial infections indeed leave characteristic disease-specific ‘immune fingerprints’ of diagnostic and prognostic value. Local fingerprints not only discriminated between episodes of culture-negative and culture-positive PD-associated peritonitis but also predicted infections caused by Gram− or Gram+ bacteria. HPMC play an important role in maintaining homeostasis of the peritoneal immunity. Our data revealed the regulation of Vγ9/Vδ2 T cells by HPMC and demonstrated that resting HPMC were potent suppressors of Vγ9/Vδ2 T-cell cytokine production and proliferation in the presence of HMB-PP. Collectively, these findings improve our insight into the complex cellular interactions in PD-associated peritonitis and peritoneal homeostasis, identify novel biomarkers of possible diagnostic and predictive value and highlight new avenues for therapeutic intervention.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:567360 |
| Date | January 2012 |
| Creators | Lin, Chan-Yu |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/37303/ |
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