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Increased plasma mannose binding lectin levels are associated with bronchiolitis obliterans after lung transplantation

Creators: Budd, Steven J, Aris, Robert M, Medaiyese, Ayorinde A, Tilley, Stephen L, Neuringer, Isabel P

File Type: pdf | Filesize: 2.1 MB | Date Added: 2012-09-12 | Date Created: 2012-07-04

AbstractBackgroundLong-term lung allograft survival is limited by bronchiolitis obliterans syndrome (BOS). Mannose binding lectin (MBL) belongs to the innate immune system, participates in complement activation, and may predispose to graft rejection. We investigated mannose binding (MBL) during cold ischemia and in tissue samples from explanted lungs with BOS, and assessed MBL and complement proteins in plasma post-lung transplantation relative to BOS staging.MethodsMBL was detected by immunohistochemistry lung tissue at the time of cold ischemia and in samples with BOS. MBL was assayed in the peripheral blood of 66 lung transplant patients transplanted between 1990&#8211;2007.ResultsMBL localized to vasculature and basement membrane during cold ischemia and BOS. Patients further out post-lung transplant&#8201;&gt;&#8201;5&#8201;years (n&#8201;=&#8201;33), had significantly lower levels of MBL in the blood compared to lung transplant patients&#8201;&lt;&#8201;5&#8201;years with BOS Op-3 (n&#8201;=&#8201;17), 1738&#8201;&#177;&#8201;250&#8201;ng/ml vs 3198&#8201;&#177;&#8201;370&#8201;ng/ml, p&#8201;=&#8201;0.027, and similar levels to lung transplant patients&#8201;&lt;&#8201;5&#8201;years with BOS 0 (n&#8201;=&#8201;16), 1738&#8201;&#177;&#8201;250&#8201;ng/ml vs 1808&#8201;&#177;&#8201;345&#8201;ng/ml. MBL levels in all BOS 0 (n&#8201;=&#8201;30) vs. all BOS Op-3 (n&#8201;=&#8201;36) were 1378&#8201;&#177;&#8201;275&#8201;ng/ml vs. 2578&#8201;&#177;&#8201;390&#8201;ng/ml, p&#8201;=&#8201;0.001, respectively. C3 plasma levels in BOS 0 (n&#8201;=&#8201;30) vs. BOS Op-3 (n&#8201;=&#8201;36) were 101&#8201;&#177;&#8201;19.8&#8201;mg/ml vs. 114&#8201;&#177;&#8201;25.2&#8201;mg/ml, p&#8201;=&#8201;0.024, respectively.ConclusionsMBL localizes within the lung during graft ischemia and BOS, higher levels of plasma MBL are associated with BOS Op-3 and&#8201;&lt;&#8201;5&#8201;years post-transplant, and higher level of plasma complement protein C3 was associated with BOS Op-3 clinical status. MBL may serve as a biomarker for poorer outcome post-lung transplantation.