The risk of infection after transplantation changes over time, particularly with modifications in immunosuppression. Unfortunately, no assays accurately measure a patient’s risk of infection. Currently, therefore, the clinician assesses a recipient’s risk of infection while considering the risk of allograft rejection, the intensity of immunosuppression, and other factors that may contribute to his or her susceptibility to infection. Prophylactic strategies are based on the patient’s known or likely exposures to infection according to the results of serologic testing and epidemiologic history. The risk of infection in the transplant recipient is a continuous function of the interplay between these factors.

https://nuhem.com/emlinks/LLSA%20Articles%202013/Infection%20in%20solid%20organ%20transplant%20recipients.pdf

Infection in Solid-Organ Transplant Recipients

Introduction of new innovative immunosuppressive strategies has been the milestone of the recent evolution of intestinal and multivisceral transplantation. With new insights into the mechanisms of organ engraftment and acquired tolerance, the Pittsburgh tolerogenic protocol was recently introduced and consisted of two main therapeutic principles: recipient pretreatment with lymphoid ablating antibodies and minimal post-transplant immunosuppression with tacrolimus monotherapy. The reported herein improved survival and the striking ability to wean immunosuppression among the intestinal and multivisceral recipients pretreated with a single-dose of Thymoglobulin (rATG) or Campath-1H (alemtuzumab) supports our working hypothesis with successful induction of variable tolerance. It is important, however, that careful monitoring of subtle histologic changes in serial endoscopic-guided mucosal biopsies be carried out for early diagnosis of allograft immune activation with prompt restoration of the baseline immunosuppressive therapy. Future scientific discoveries with better understanding of the mechanisms of immune tolerance and clinical introduction of reliable assays will increase the chance and safety of achieving complete tolerance among the intestinal and other solid organ recipients. This review will focus on the historic evolution of the immunosuppressive and other management strategies utilized for the intestinal and multivisceral recipients at the University of Pittsburgh with special reference to allograft immunity and the successful achievement of partial tolerance.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-2277.2008.00785.x

Evolution of the immunosuppressive strategies for the intestinal and multivisceral recipients with special reference to allograft immunity and achievement of partial tolerance.

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.

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

Therapeutic drug monitoring is a well-established approach in transplantation medicine to guide immunosuppressive therapy. However, it cannot always predict the effects of immunosuppressive drugs on immune cells, because it does not reflect any aspect of an individual patient's immune system. Pharmacodynamic monitoring is a more recent strategy to provide information about the biologic effect of a specific drug or drug combination on the individual transplant patient. Currently, there is a large number of different biomarkers that either directly (specific markers) or indirectly (global markers) relate to the pharmacodynamic effects of immunosuppressive drugs and are under investigation as potential candidates to be introduced in clinical practice. Such biomarkers may be useful to identify patients at risk of developing acute rejection, infection, or cancer as well as patients who are suitable for minimization of immunosuppressant therapy and may be helpful to manage the timing and rate of immunosuppressant weaning. Serial longitudinal monitoring may allow maintenance of an individualized immunosuppressive regimen. Thus, biomarker monitoring is a potential complementary tool to therapeutic drug monitoring. This review summarizes the current state of knowledge about the use of a number of global or drug-specific pharmacodynamic biomarkers. It is not a comprehensive overview of the literature available, but rather an evidence-based reflection by experts who are intensively involved in scientific work in this field.

Biomarkers as a tool for management of immunosuppression in transplant patients.

Clinical-nutritional autonomy is the ultimate goal of patients with intestinal failure (IF). Traditionally, patients with IF have been relegated to lifelong parenteral nutrition (PN) once surgical and medical rehabilitation attempts at intestinal adaptation have failed. Over the past two decades, however, outcome improvements in intestinal transplantation have added another dimension to the therapeutic armamentarium in the field of gut rehabilitation. This has become possible through relentless efforts in the standardization of surgical techniques, advancements in immunosuppressive therapies and induction protocols and improvement in postoperative patient care. Four types of intestinal transplants include isolated small bowel transplant, liver-small bowel transplant, multivisceral transplant and modified multivisceral transplant. Current guidelines restrict intestinal transplantation to patients who have had significant complications from PN including liver failure and repeated infections. From an experimental stage to the currently established therapeutic modality for patients with advanced IF, outcome improvements have also been possible due to the introduction of tacrolimus in the early 1990s. Studies have shown that intestinal transplant is cost-effective within 1-3 years of graft survival compared with PN. Improved survival and quality of life as well as resumption of an oral diet should enable intestinal transplantation to be an important option for patients with IF in addition to continued rehabilitation. Future research should focus on detecting biomarkers of early rejection, enhanced immunosuppression protocols, improved postoperative care and early referral to transplant centers.

Current status of intestinal and multivisceral transplantation.

Monitoring immune function during tacrolimus tapering in small bowel transplant recipients

Routine Donor Specific Antibody Monitoring in Heart Transplant Recipients - Is There a Role?

Combined Plasmapheresis and Complement Inhibition in a Highly Allosensitized Cardiac Transplant Recipient

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Monitoring immune function during tacrolimus tapering in small bowel transplant recipients

Routine Donor Specific Antibody Monitoring in Heart Transplant Recipients - Is There a Role?

Combined Plasmapheresis and Complement Inhibition in a Highly Allosensitized Cardiac Transplant Recipient