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

Fernández-Ruiz M, Kumar D, Humar A - Clin Transl Immunology (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Transplant Infectious Diseases, Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, University of Toronto , Toronto, Ontario, Canada.

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.

No MeSH data available.


Related in: MedlinePlus

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).
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fig2: 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).

Mentions: The administration of lymphocyte-depleting agents (that is, rabbit polyclonal antithymocyte globulin or anti-CD52 (alemtuzumab) monoclonal antibody) for induction therapy or treatment of rejection is a well-established risk factor for the occurrence of post-transplant infection.44 Similar to monitoring of patients with human immunodeficiency virus infection, the kinetics of certain peripheral blood lymphocyte sub-populations have been explored as the basis for post-transplant immune monitoring. Calarota et al.45 regularly assessed the CD4+ and CD8+ T-cell numbers during the first 8 months after kidney and heart transplantation and reported that those patients who developed opportunistic infections—because of CMV in most of cases—had lower counts as compared with those without. In the specific setting of human immunodeficiency virus patients undergoing kidney transplantation, the presence of a CD4+ T-cell count <200 cells μl−1 was associated with the occurrence of opportunistic or severe infection.46 Various authors have consistently shown that the risk of Pneumocystis jiroveci pneumonia after kidney transplantation is increased in recipients with low CD4+ T-cell counts,47, 48, 49 and it has been suggested that the dynamics of peripheral blood lymphocyte sub-population may help to guide the duration of prophylaxis with trimethoprim-sulfamethoxazole, similarly to human immunodeficiency virus patients.48 In a recent prospective study with 82 liver transplant recipients, having a CD4+ T-cell count 300 cells μl−1 at month 1 increased significantly the risk of subsequent opportunist infection (Fernández-Ruiz M, 2013, unpublished data; Figure 2). Similarly, the depletion of the CD4+ T-cell subset is also useful to predict de novo post-transplant malignancy—another complication clearly related to over-immunosuppression—in the long term.50, 51, 52 The enumeration of peripheral blood lymphocyte sub-populations is technically simple, has a short turnaround time and may be performed in a fully automated way. In addition, the interpretation of its results appears easily intuitive to the clinician. However, we still need more studies to validate the prognostic accuracy of this strategy in different types of transplant recipients who have or have not received lymphocyte-depleting antibodies.


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

Fernández-Ruiz M, Kumar D, Humar A - Clin Transl Immunology (2014)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4232060&req=5

fig2: 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).
Mentions: The administration of lymphocyte-depleting agents (that is, rabbit polyclonal antithymocyte globulin or anti-CD52 (alemtuzumab) monoclonal antibody) for induction therapy or treatment of rejection is a well-established risk factor for the occurrence of post-transplant infection.44 Similar to monitoring of patients with human immunodeficiency virus infection, the kinetics of certain peripheral blood lymphocyte sub-populations have been explored as the basis for post-transplant immune monitoring. Calarota et al.45 regularly assessed the CD4+ and CD8+ T-cell numbers during the first 8 months after kidney and heart transplantation and reported that those patients who developed opportunistic infections—because of CMV in most of cases—had lower counts as compared with those without. In the specific setting of human immunodeficiency virus patients undergoing kidney transplantation, the presence of a CD4+ T-cell count <200 cells μl−1 was associated with the occurrence of opportunistic or severe infection.46 Various authors have consistently shown that the risk of Pneumocystis jiroveci pneumonia after kidney transplantation is increased in recipients with low CD4+ T-cell counts,47, 48, 49 and it has been suggested that the dynamics of peripheral blood lymphocyte sub-population may help to guide the duration of prophylaxis with trimethoprim-sulfamethoxazole, similarly to human immunodeficiency virus patients.48 In a recent prospective study with 82 liver transplant recipients, having a CD4+ T-cell count 300 cells μl−1 at month 1 increased significantly the risk of subsequent opportunist infection (Fernández-Ruiz M, 2013, unpublished data; Figure 2). Similarly, the depletion of the CD4+ T-cell subset is also useful to predict de novo post-transplant malignancy—another complication clearly related to over-immunosuppression—in the long term.50, 51, 52 The enumeration of peripheral blood lymphocyte sub-populations is technically simple, has a short turnaround time and may be performed in a fully automated way. In addition, the interpretation of its results appears easily intuitive to the clinician. However, we still need more studies to validate the prognostic accuracy of this strategy in different types of transplant recipients who have or have not received lymphocyte-depleting antibodies.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Transplant Infectious Diseases, Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, University of Toronto , Toronto, Ontario, Canada.

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.

No MeSH data available.


Related in: MedlinePlus