Mannose-binding lectin deficiency linked to cytomegalovirus (CMV) reactivation and survival in lung transplantation

Abstract

SummaryDespite the use of immunosuppressives mainly influencing T and B cell responses, the prevalence of the bronchiolitis obliterans syndrome (BOS) after lung transplantation is high. Mannose-binding lectin (MBL) is a pattern recognition molecule of complement and an important component of the innate immunity. MBL is associated with rejection, infection and survival in other solid organ transplantations. In this study the relation between functional MBL levels and cytomegalovirus (CMV) reactivations and the development of BOS and survival after lung transplantation was investigated. MBL levels were measured in 85 patients before and in 57 of these patients after lung transplantation. The relation of MBL on survival, CMV reactivation and the development of BOS were investigated with Kaplan-Meier (log-rank) survival analysis. MBL levels decreased on average by 20% (P < 0·001) after transplantation and eventually returned to pretransplant levels. Fourteen of the 85 patients had deficient pretransplant MBL levels and these patients had a tendency towards a better survival compared to those with normal MBL levels (P = 0·08). Although no correlation was found between MBL deficiency and the development of BOS, more CMV reactivations occurred in recipients with deficient versus normal levels of MBL (P = 0·03). Our results suggest that MBL deficiency is associated with CMV reactivations and a longer overall survival, but not with the development of BOS.

The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation

“…75 Polymorphisms in genes for mannose binding lectin (MBL) associated with low MBL production and ficolin-2 may also be associated with increased risk of CMV disease. [76][77][78] A multicenter study has recently demonstrated that patients with lower complement C3 levels (<80 mg/dL) early (7 days) after transplantation have a greater risk for CMV disease. 79 Transplant recipients with an IL-28B single nucleotide polymorphism were found to be at significantly less risk of CMV replication.…”

Herpesvirus Respiratory Infections in Immunocompromised Patients: Epidemiology, Management, and Outcomes

“…27 Finally, certain host genetic factors have also been shown to confer variable risks for CMV infection. [82][83][84] Polymorphisms in genes of the innate immune system, including those for Toll-like receptors and mannose-binding lectin 83,85,86 have been shown to affect the risk for CMV in organ transplant recipients. Deficiencies in CMV-specific Tlymphocyte responses 87 and hypogammaglobulinemia after transplantation 88 have also been identified as risk factors for CMV disease.…”

Low Levels of Mannan-Binding Lectin or Ficolins Are Not Associated with an Increased Risk of Cytomegalovirus Disease in HIV-Infected Patients

“…Another study failed to find a correlation between CMV replication in newborns and the frequencies of MBL genotypes [44]. After transplantation several studies have highlighted MBL deficiency as a potential risk factor for CMV replication and disease [29,31,32,45,46]. Manuel et al reported an increased risk of CMV disease in a small study of high-risk CMV sero-negative recipients of CMV sero-positive kidney grafts with functional MBL deficiency [31].…”

“…Manuel et al reported an increased risk of CMV disease in a small study of high-risk CMV sero-negative recipients of CMV sero-positive kidney grafts with functional MBL deficiency [31]. The presence of MBL and ficolin-2 polymorphisms in the liver and lung transplant recipients were associated with increased CMV replication in the recipient [29,45,46]. However, in other transplant cohorts, either structural haplotype AA had higher rates of CMV disease compared to patients with A/O or O/O [34].…”