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Evaluation of the role of Mannose binding lectin in HIV infected patients with and without CMV disease

English title Evaluation of the role of Mannose binding lectin in HIV infected patients with and without CMV disease
Applicant Trendelenburg Marten
Number 132955
Funding scheme Project funding (special)
Research institution Klinik Innere Medizin Universitätsspital Basel
Institution of higher education University of Basel - BS
Main discipline Clinical Immunology and Immunopathology
Start/End 01.10.2010 - 30.09.2011
Approved amount 88'869.00
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All Disciplines (2)

Discipline
Clinical Immunology and Immunopathology
Internal Medicine

Keywords (6)

Complement; HIV; CMV; Cytomegalovirus; Large nested project; Swiss HIV Cohort Study

Lay Summary (English)

Lead
Lay summary
Cytomegalovirus (CMV) latently infects 40% to 70% of the healthy population. A functioning immune system is important to control CMV replication and helps to prevent severe disease in the majority of people. In HIV infected patients with advanced disease, the number of specific immune cells is reduced. These cells can be measured in the blood serves as a marker for the extend of the immunosuppression caused by the HIVirus. Numbers of these cells below 100/uL are associated with an increased risk for CMV disease in patients with underlying HIV infection and therefore seem to be essential in the battly against the CMVirus. However, current data indicate the potential influence of other probably innate immunological factors during replication of the CMVirus, especially in the context of a reduced cellular control.The complement protein mannose binding lectin (MBL) is an important part of the innate immune system. Interestingly up to one third of the general population is not able to produce sufficient amounts of MBL and thus can be considered as being MBL deficient. Data from solid organ transplant recipients (such as those receiving a kidney transplant) has shown, that MBL serum levels <500ng/mL are associated with CMV disease after transplantation. However, the importance of MBL in HIV positive patients in order to prevent CMV disease needs to be defined. Therefore, we want to study the role of MBL by measuring blood MBL concentrations in HIV patients with CMV disease compared to HIV patients that did not develop CMV disease. The hypothesis is that patients who developped CMV disease had lower blood MBL concentrations. The results will help to understand the role of different components of our immune system and eventually will lead to better treatment strategies of CMV disease. This study is possible thanks to the existance of the Swiss HIV cohort study that follows HIV patients in Switzerland since many years.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Publications

Publication
Low levels of mannan-binding lectin or ficolins are not associated with an increased risk of cytomegalovirus disease in HIV-infected patients.
Egli Adrian, Trendelenburg Marten, Battegay Manuel, Osthoff Michael, Thiel Steffen, Schäfer Juliane (2013), Low levels of mannan-binding lectin or ficolins are not associated with an increased risk of cytomegalovirus disease in HIV-infected patients., in PLoS One, 8(1), e51983.

Collaboration

Group / person Country
Types of collaboration
Swiss HIV cohort study Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Associated projects

Number Title Start Funding scheme
134900 Waste disposal in the pathogenesis of Systemic Lupus Erythematosus (SLE): The role of complement C1q and anti-C1q antibodies 01.04.2011 Project funding

Abstract

Background:Cytomegalovirus (CMV) latently infects 40% to 70% of the healthy population. Sufficient CMV-specific immunity is important to control CMV replication in healthy individuals and immuno-suppressed patients. In HIV infected patients, CD4 T-cell frequency serves as a surrogate marker for immunosuppression. CD4 T-cells below 100/uL are associated with an increased risk for CMV disease. However, data underline the controversy of CMV-specific T-cells in HIV infected patients. The predictive value of CMV-specific T-cells in AIDS patients for CMV-retinitis seems to be poor, indicating the potential influence of other probably innate immunological factors during CMV replication, especially in the context of a reduced T-cell control.The complement system is an important part of the innate immune system. Activation of the cascade results in further inflammation, opsonisation of the pathogen and the formation of the membrane attack complex. Complement mannose binding lectin (MBL) forms homo-trimers associating to carbohydrate structures on bacteria, viruses and fungi. The binding of MBL initiates cleavage C3 molecules and induction of the following cascade. Despite being a liver-produced protein MBL shows only a very weak acute phase reaction. Therefore, a single determination in sera of adult patients usually provides stable information on the lifetime level. Interestingly, independent of MBL the ficolin family also utilizes the same activation molecules of the complement cascade. A functional deficiency of MBL (and/or ficolins 1-3) might be an adding risk factor for a reduced CMV control. Data from solid organ transplant recipients has shown, that MBL serum levels <500ng/mL are associated with CMV disease after transplantation in patients with a high risk constellation. The value of MBL and ficolin levels in HIV positive patients in correlation to CMV disease needs to be defined.Study Aims:1.Measurement of MBL and ficolin serum/plasma levels in HIV infected patients with and without CMV disease.2.Characterisation of MBL and ficolin as a potential risk factor for CMV disease and description of its clinical impact.Study Design:Nested case control study with the following groups:Group A: HIV infected patients with CMV diseaseGroup B: HIV infected patients without CMV disease (matched controls)Groups A and B will be evaluated in regard to exposure to varying levels of MBL and ficolin 1-3 as possible risk factors for the development of symptomatic CMV disease in HIV-infected patients with compromised immune function. Patients will be time-matched with CMV positive controls in regard to CD4 T-cell counts, availability of samples from the Swiss HIV Cohort Study (SHCS) repository and antiretroviral treatment status (at three levels).
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