https://onlinelibrary.wiley.com/doi/pdf/10.1111/ajt.14208

Infection in Organ Transplantation

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.

State-of-the-Art Monitoring of Cytomegalovirus-Specific Cell-Mediated Immunity After Organ Transplant: A Primer for the Clinician

Immunity after Organ Transplant - A Primer for the Clinician

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.

https://onlinelibrary.wiley.com/doi/pdf/10.1038/cti.2014.3

Clinical immune-monitoring strategies for predicting infection risk in solid organ transplantation.

Management of cytomegalovirus infection in solid organ transplant recipients: SET/GESITRA-SEIMC/REIPI recommendations

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.

Carolyn Bentlejewski

Papers

Experience with immune monitoring in lung transplant recipients: correlation of low immune function with infection.