Experience with immune monitoring in lung transplant recipients: correlation of low immune function with infection.
TL;DR: Cylex ImmuKnow assay monitoring has the potential to identify the patients atrisk of developing infection and those colonized with fungus that are at risk of developing disease.
Abstract: Background. Lung transplants, in particular, have the highest rate of infections among solid organ transplant recipients. However, there is no existing objective measure to predict the development of infections. We report the correlation between Cylex ImmuKnow (ng/mL ATP) values and various infectious syndromes in a large prospective cohort of lung transplant recipients. Methods. We followed up 175 lung transplants that developed 129 infectious episodes. Multiple logistic regression analysis was performed; generalized estimating equations were used to determine the odds ratio for infections. Results. The median ImmuKnow values in cytomegalovirus disease (49.3 ng/mL ATP), viral infection (70 ng/mL ATP), and bacterial pneumonia (92 ng/mL ATP) were significantly different from stable state (174.8 ng/mL ATP). The median ImmuKnow values of fungal disease (85 ng/mL ATP) and tracheobronchitis (123 ng/mL ATP) had a tendency to be lower than stable state (P=0.10), whereas patients with fungal colonization had comparable ImmunKnow values (167 vs. 174.8 ng/mL ATP). Of the patients colonized with fungus who subsequently developed fungal disease within 100 days, the median value of ImmuKnow was significantly lower than in those who did not develop fungal disease (22.5 vs. 183.5 ng/mL ATP; P<0.0001). Generalized estimating equation regression analysis showed ImmuKnow values less than or equal to 100 ng/mL ATP to be an independent predictor of infections (odds ratio 2.81). Conclusions. Cylex ImmuKnow assay monitoring has the potential to identify the patients at risk of developing infection and those colonized with fungus that are at risk of developing disease.
Citations
More filters
TL;DR: Transplant infectious disease remains a key to the clinical and scientific investigation of organ transplantation and application of quantitative molecular microbial assays and advanced antimicrobial therapies have advanced care.
453 citations
Cites background from "Experience with immune monitoring i..."
...Other measures of “global” immune function lack the desired predictive values for infectious risk (39)....
[...]
TL;DR: In this article, the authors discuss the measurement of CMV-specific T-cell responses and their clinical impact on the management of C-Cytomegalovirus after organ transplantation.
Abstract: Cytomegalovirus (CMV) is one of the most common infections after solid organ transplantation. Improved assays to predict viral replication and disease would help refine current preventive strategies. Monitoring of CMV-specific T-cell responses may help guide clinical decision making. Several techniques are now available to quantify CMV-specific T-cell responses, including flow cytometry, enzyme-linked immunosorbent spot assay, and enzyme-linked immunosorbent assay. Standardization and validation of these assays have the potential to significantly change the monitoring and treatment of CMV and further personalize CMV prevention strategies. In this review, we discuss the measurement of CMV-specific T-cell responses and their clinical impact on the management of CMV after organ transplantation.
122 citations
01 Jan 2012
TL;DR: Several techniques are now available to quantify CMV-specific T-cell responses, including flow cytometry, enzyme- linked immunosorbent spot assay, and enzyme-linked immunOSorbent assay, which have the potential to significantly change the monitoring and treatment of CMV.
Abstract: Cytomegalovirus (CMV) is one of the most common infections after solid organ transplantation. Improved assays to predict viral replication and disease would help refine current preventive strategies. Monitoring of CMV-specific T-cell responses may help guide clinical decision making. Several techniques are now available to quantify CMV-specific T-cell responses, including flow cytometry, enzyme-linked immunosorbent spot assay, and enzyme-linked immunosorbent assay. Standardization and validation of these assays have the potential to significantly change the monitoring and treatment of CMV and further personalize CMV prevention strategies. In this review, we discuss the measurement of CMV-specific T-cell responses and their clinical impact on the management of CMV after organ transplantation.
115 citations
Cites background from "Experience with immune monitoring i..."
...predictive of infections in general, the assay is not pathogen specific [20]....
[...]
TL;DR: Clinical evidence to date supporting the use of approaches to the post‐transplant immune status, based on interferon‐γ release assays, intracellular cytokine staining or main histocompatibility complex‐tetramer technology is summarized.
Abstract: Infectious complications remain a leading cause of morbidity and mortality after solid organ transplantation (SOT), and largely depend on the net state of immunosuppression achieved with current regimens. Cytomegalovirus (CMV) is a major opportunistic viral pathogen in this setting. The application of strategies of immunological monitoring in SOT recipients would allow tailoring of immunosuppression and prophylaxis practices according to the individual's actual risk of infection. Immune monitoring may be pathogen-specific or nonspecific. Nonspecific immune monitoring may rely on either the quantification of peripheral blood biomarkers that reflect the status of a given arm of the immune response (serum immunoglobulins and complement factors, lymphocyte sub-populations, soluble form of CD30), or on the functional assessment of T-cell responsiveness (release of intracellular adenosine triphosphate following a mitogenic stimulus). In addition, various methods are currently available for monitoring pathogen-specific responses, such as CMV-specific T-cell-mediated immune response, based on interferon-γ release assays, intracellular cytokine staining or main histocompatibility complex-tetramer technology. This review summarizes the clinical evidence to date supporting the use of these approaches to the post-transplant immune status, as well as their potential limitations. Intervention studies based on validated strategies for immune monitoring still need to be performed.
107 citations
Carlos III Health Institute1, Complutense University of Madrid2, University of Castilla–La Mancha3, Instituto Politécnico Nacional4, University of Barcelona5, University of Alberta6, University of Cantabria7, Autonomous University of Barcelona8, Hospital General Universitario Gregorio Marañón9, University of Valencia10, Spanish National Research Council11
TL;DR: A panel of experts revised the evidence on CMV management, including immunological monitoring, diagnostics, prevention, vaccines, indirect effects, treatment, drug resistance, immunotherapy, investigational drugs, and pediatric issues, and this document summarizes the recommendations.
93 citations
References
More filters
Journal Article•
TL;DR: This article summarizes the updated classification for pulmonary allograft rejection, which is based on perivascular and interstitial mononuclear infiltrates and divided into bronchiolitis obliterans--active or inactive--and vascular atherosclerosis--accelerated arterial or venous sclerosis.
Abstract: In 1990, an international grading scheme for the grading of pulmonary allograft rejection was instituted. The use of this classification has resulted in a uniformity of grading which has allowed inter-institutional collaborations and communication unique in allograft monitoring. In 1995 an expanded group of international pathologists convened and revised the original proposal. This article summarizes the updated classification for pulmonary allograft rejection. In brief, acute rejection is based on perivascular and interstitial mononuclear infiltrates. Each grade of acute rejection should mention the presence of coexistent airway inflammation, the intensity of which may also be graded. Chronic rejection is divided into bronchiolitis obliterans--active or inactive--and vascular atherosclerosis--accelerated arterial or venous sclerosis.
844 citations
"Experience with immune monitoring i..." refers methods in this paper
...The rejection episodes were classified as per The International Society for Heart & Lung Transplantation criteria (10)....
[...]
TL;DR: Recommendations for screening, monitoring and reporting recommendations for common transplant‐associated infections were developed for use in clinical trials evaluating immunosuppressive strategies to provide clinically relevant definitions for tracking infectious complications occurring in participants in immunOSuppressive trials.
433 citations
"Experience with immune monitoring i..." refers background in this paper
...All infectious syndromes were classified as per standardized criteria (9)....
[...]
TL;DR: Each year, 55,000 organ transplants are performed worldwide, and the number of living organ recipients is now estimated to be over 300,000, with most of these transplant recipients remaining on immunosuppressive drugs for the remainder of their lives to prevent rejection episodes.
Abstract: Each year, 55 000 organ transplants are performed worldwide. Cumulatively, the number of living organ recipients is now estimated to be over 300 000. Most of these transplant recipients will remain on immunosuppressive drugs for the remainder of their lives to prevent rejection episodes. Controlled doses of these drugs are required to prevent over-medication, which may leave the patient susceptible to opportunistic infection and drug toxicity effects, or under-dosing, which may lead to shortened graft survival because of rejection episodes. This paper describes the result of a multicenter study conducted at the Universities of Pittsburgh, Alabama and Maryland to evaluate an in vitro assay (CylexTM Immune Cell Function Assay) for the measurement of global immune response in transplant patients receiving immunosuppressive therapy. The assay uses a whole blood sample to maintain the presence of the drug during incubation. Following overnight incubation of blood with phytohemagglutinin (PHA), CD4 cells are selected using paramagnetic particles coated with a monoclonal antibody to the CD4 epitope. The CD4-positive cells are targeted as major immunosuppressive drugs are designed to specifically inhibit T-cell activation which has been implicated in rejection. The data generated at these three sites were submitted in support of an Food and Drug Association (FDA) application for the use of this assay in the detection of cell-mediated immunity in an immunosuppressed population. The assay was cleared by the FDA on April 2, 2002. This cross-sectional study was designed to establish ranges for reactivity of this bioassay in the assessment of functional immunity for an individual solid organ recipient at any point in time.
245 citations
"Experience with immune monitoring i..." refers methods in this paper
...Immune responses were measured using an US Food and Drug Administration-approved assay for T-cell function, ImmuKnow (Cylex, Columbia, MD) according to the manufacturer’s instructions (11)....
[...]
TL;DR: Patients who received alemtuzumab for the treatment of allograft rejection were significantly more likely to develop an OI, compared with patients who received the drug for induction therapy only, and such data have implications for new antimicrobial prophylactic strategies.
Abstract: Background. Alemtuzumab is being increasingly used for the prevention and/ or treatment of acute allograft rejection in organ transplant recipients. We assessed the risks of infection in, to our knowledge, the largest cohort and broadest range of organ transplant recipients yet reported to have received alemtuzumab.
227 citations
"Experience with immune monitoring i..." refers background in this paper
...The use of alemtuzumab has resulted in a favorable outcome in lung transplant recipients although the risk of infection remains significantly high (7, 13)....
[...]
TL;DR: Voriconazole prophylaxis can be used in preventing IA in lung transplant recipients and regular monitoring of liver enzymes and serum concentrations of calcineurin inhibitors are required to avoid hepatotoxicity and nephrotoxicity.
196 citations
"Experience with immune monitoring i..." refers background in this paper
...Primary mismatches for CMV (D /R ) 37 (22)...
[...]
...The factors responsible for progression from colonization to invasive disease are not known, resulting in universal antifungal prophylaxis in lung transplant recipients (22, 24, 25)....
[...]
...Fungal colonization with Aspergillus is a known risk factor for the development of subsequent invasive aspergillosis in lung transplant recipients; however, the positive predictive values of posttransplant Aspergillus colonization is only 28% (22, 23)....
[...]