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

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

doi:10.1186/1465-9921-13-56

Abstract

BackgroundLong-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 1990–2007.ResultsMBL localized to vasculature and basement membrane during cold ischemia and BOS. Patients further out post-lung transplant > 5 years (n = 33), had significantly lower levels of MBL in the blood compared to lung transplant patients < 5 years with BOS Op-3 (n = 17), 1738 ± 250 ng/ml vs 3198 ± 370 ng/ml, p = 0.027, and similar levels to lung transplant patients < 5 years with BOS 0 (n = 16), 1738 ± 250 ng/ml vs 1808 ± 345 ng/ml. MBL levels in all BOS 0 (n = 30) vs. all BOS Op-3 (n = 36) were 1378 ± 275 ng/ml vs. 2578 ± 390 ng/ml, p = 0.001, respectively. C3 plasma levels in BOS 0 (n = 30) vs. BOS Op-3 (n = 36) were 101 ± 19.8 mg/ml vs. 114 ± 25.2 mg/ml, p = 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 < 5 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.

Highlights

Long-term lung allograft survival is limited by bronchiolitis obliterans syndrome (BOS)
While surfactant proteins A and D may be protective to the lung allograft after lung transplantation, as reduced levels are associated with BOS [11], Mannose binding lectin (MBL) may be either protective or harmful depending upon infectious or autoimmune risk
Immunohistochemistry for MBL was performed on sections of lung allograft tissue from patients at the time of lung allograft implantation paralleling cold ischemia, (n = 6) (Figure 1), explanted lung tissue from patients retransplanted for bronchiolitis obliterans syndrome (BOS, n = 8) (Figure 2) and non-transplant patients with diffuse alveolar damage (DAD, n = 6) (Figure 3), in accordance with IRB protocols

Summary

Introduction

Long-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. Lung transplantation for end-stage lung disease is a successful treatment, long-term survival is limited by bronchiolitis obliterans (BOS). Mannose binding lectin (MBL), a member of the collectin family (surfactant proteins A and D, mannose binding lectin, MBL) participates in activation of the alternative pathway of complement, bridging adaptive and innate immunity [10]. While surfactant proteins A and D may be protective to the lung allograft after lung transplantation, as reduced levels are associated with BOS [11], MBL may be either protective or harmful depending upon infectious or autoimmune risk. Low serum MBL levels, often due to genetic polymorphisms, have been associated with increased risk of infection, more severe manifestation of cystic fibrosis lung disease, and autoimmunity, while high levels exacerbate inflammatory diseases and diabetic nephropathy [19,20,21,22,23,24,25,26,27,28]

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Conclusion