|dc.description.abstract||My research investigated the distribution of antimicrobial peptides (cathelicidin and β-defensin 2), vitamin D and the inflammatory marker procalcitonin, between systemic and localised respiratory levels in stable bronchiectasis patients. Bronchiectasis is a localised chronic lung disease that is characterised by acute reoccurring lower tract respiratory infections. Non-cystic fibrosis bronchiectasis patient serum and sputum samples were collected as part of an ongoing clinical trial. This trial is investigating the usefulness of Tiotropium for the treatment of bronchiectasis.
Antimicrobial peptides are a fundamental component of the innate immune system. The innate immune system is vital in providing the first line of defence against pathogens. At epithelia sites this is more so, as cells are often in direct contact with the environment. Both cathelicidin and β-defensin 2 expression has been found to be upregulated by the active vitamin D metabolite, 1,25-dihydroxyvitamin D. This research also aimed to determine if vitamin D deficiency is prevalent in bronchiectasis, and how these levels correspond with cathelicidin and hBD-2. Lastly, whether procalcitonin, a known inflammatory marker of bacterial infections is a suitable biomarker for bronchiectasis. Other inflammatory markers have been shown to be consistently elevated in stable bronchiectasis patients.
The use of commercial ELISA kits demonstrated the notion of systemic levels not being representative of localised levels. Both of the antimicrobial peptides, cathelicidin and β-defensin 2, show elevated sputum levels consistent with bronchiectasis being a localised condition. Contrastingly, vitamin D metabolites are found to be lower in the airways. This is predicted to be due to the majority of vitamin D metabolites being protein bound in circulation, thereby affecting their tissue distribution. Stable bronchiectasis patients do not have persistently elevated serum procalcitonin levels but procalcitonin levels are significantly higher in the sputum.
Our findings report that suboptimal vitamin D levels, but not vitamin D deficiency, were prevalent in stable bronchiectasis patients. No correlations were found between 25-hydroxyvitamin D and antimicrobial peptide concentrations, consistent with other studies findings. However, localised levels of the active form, 1,25-dihydroxyvitamin D, were correlated with localised cathelicidin (CAMP) levels but not β-defensin 2.
Future work should focus on the hormonal form, 1,25-dihydroxyvitamin D, if an in vivo association with antimicrobial peptides is to be found. A number of factors can influence vitamin D bioavailability, including, known single nucleotide polymorphisms in the vitamin D receptor and vitamin D binding protein.||