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CMV Immune Monitoring in SOT Recipients
Approaches to CMV Immune Monitoring in Solid Organ Transplant Recipients

Released: November 10, 2023

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Key Takeaways
  • Measuring CMV immunity in solid organ transplant recipients can help healthcare professionals understand their risk of CMV infection.
  • Potential uses for CMV cell-mediated immunity include determining duration of primary prophylaxis, risk for CMV infection progression, and potential need for secondary prophylaxis.

Cytomegalovirus (CMV) is one of the most common opportunistic infections in solid organ transplant (SOT) recipients and can cause considerable complications, including end-organ damage resulting in significant morbidity and mortality. To better understand the risk of CMV infection faced by SOT recipients, there is interest in measuring the immune response to the virus to assess whether the patient is susceptible and at risk for infection or can mount an immune response.

CMV Cell-Mediated Immunity
Measuring cell-mediated immunity (CMI) is a method to determine a patient’s risk for CMV infection. CMV-CMI assays do this by quantifying the total number of interferon-γ‒producing immune cells (eg, CD4+ and/or CD8+) or the amount of interferon-γ secreted by these cells in response to CMV antigens or other peptides.

Immune responses measured with these assays have been associated with various virologic outcomes. Based on the test being used, there are different thresholds for positive results. In general, a high CMV-CMI result is associated with lower incidence of CMV infection. By contrast, if a patient has no or low CMV-specific immune responses, they will have a higher risk of CMV infection. Furthermore, if patients remain negative for CMV-specific immunity despite CMV disease and treatment, they have a higher risk of relapse.

When to Consider Using CMV-CMI
What are possible indications for CMV-CMI use? Here are some scenarios where I would consider using CMV-CMI monitoring.

Primary Prophylaxis
CMV-CMI monitoring can be used to guide the duration of prophylaxis in SOT recipients who have preexisting immunity to the virus or positive CMV serology at the time of transplant. However, based on available data, it does not appear to be effective to guide prophylaxis in the highest-risk patient, such as CMV-seronegative recipients of an organ from a CMV-seropositive donor (D+/R- mismatch). In many cases, these patients receive antiviral prophylaxis so their immune system does not “see” the virus and will not develop an immune response. 

CMV Infection
Another scenario where CMV-CMI monitoring can be used is during CMV infection, alongside CMV viral load monitoring, to assess whether the patient is at high risk for progression to severe disease. For example, if a patient’s CMV-CMI assay is negative, then the risk of their CMV infection progressing to severe disease is high and would be an indication for treatment. On the other hand, if the patient has low CMV viral loads and a positive CMV-CMI assay, they are more likely to self-resolve their CMV infection without treatment.

Secondary Prophylaxis
The final indication for a CMV-CMI assay is after treatment for CMV infection when the patient’s quantitative nucleic acid amplification testing returns negative to determine risk of recurrent CMV or relapse. If CMV-CMI assay results are positive, then the risk of relapse is going to be negligible. However, if the results of the CMV-CMI assay are negative, the risk of relapse is going to be very high. In these cases, I would give these patients secondary antiviral prophylaxis.

Indeed, a negative CMV-CMI result in this situation also could suggest that these patients did not develop a CMV-specific immune response, most likely due to their intense immunosuppressive therapy, and that switching to another regimen (eg, mTOR inhibitor) or reducing the dosage of immunosuppressive therapy would be beneficial to allow the patient’s T-cells to mount an immune response against CMV. These are strategies I would consider while giving them secondary antiviral prophylaxis.

Absolute Lymphocyte Counts
The downside about CMV-CMI assays is that they are not widely available; only a few assays are commercially available in the United States.

Instead, using the absolute lymphocyte count (ALC), or the total number of lymphocytes, is another approach to assessing CMV immunity. Depending on the study you reference, an ALC <500-730 cells/μL is associated with a higher risk of CMV disease after transplantation. In another study, SOT recipients who experienced a relapse of CMV infection had lower mean ALCs compared with patients who did not experience CMV relapses. Altogether, these results imply that even in the absence of sophisticated CMV-CMI assays, a simple ALC can guide healthcare professionals in assessing a patient’s risk of developing CMV after transplant.

Your Thoughts?
How do you use immune monitoring to manage CMV in SOT recipients? Do you think CMV-CMI assays should be more widely used? Leave a comment to join the discussion.