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

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.

Keywords: cell-mediated immunity; cytomegalovirus; immune-monitoring strategies; infection; prediction; solid organ transplantation.

Figure 1

Cumulative incidences at month 6 post-transplant for overall bacterial infection, bloodstream infection (BSI) and acute pyelonephritis (APN) according to the serum IgG levels at month 1 in a prospective cohort of 271 kidney transplant recipients (modified from reference Fernández-Ruiz et al. plus personal data (Fernández-Ruiz M, 2013, unpublished data)).

Figure 2

Opportunistic infection-free survival in 82 liver transplant recipients according to the CD4⁺ T-cell count at month 1 post-transplant (P-value=0.0001; log-rank test) (Fernández-Ruiz M, 2013, unpublished data).