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A Sequential Two-Step Cell-Based Assay Predicts Immunosuppression-Related Adverse Events
François Bouchard-Boivin1, Olivier Désy1, Stéphanie Béland1
1Transplantation Unit, Renal Division, Department of Medicine, University Health Center of Quebec, Faculty of Medicine, Laval University, Quebec City, Quebec G1R 2J6, Canada; and.
Journal of Immunology (Baltimore, Md. : 1950)
|November 14, 2020
Summary
A new two-step cell-based assay effectively identifies over-immunosuppression (OIS) in transplant patients. This tool measures immune reserve by analyzing monocyte and B cell responses to EBV peptides, aiding immunotherapy optimization.
Area of Science:
- Immunology
- Transplantation Medicine
- Diagnostic Assay Development
Background:
- Immunosuppressive therapy is crucial but carries risks of serious adverse effects.
- Assessing immune reserve is vital for optimizing immunotherapy and preventing complications.
- Over-immunosuppression (OIS) increases the risk of infections and malignancies in transplant recipients.
Purpose of the Study:
- To develop and validate a sequential, two-step cell-based assay for detecting over-immunosuppression (OIS).
- To improve the specificity of OIS detection compared to existing methods.
- To identify patients at high risk of OIS for better management of immunosuppressive therapy.
Main Methods:
- Validated a sensitive assay measuring TNF-α from intermediate monocytes stimulated with EBV peptides.
- Developed a sequential, two-step assay using peripheral blood mononuclear cells (PBMCs) from kidney recipients (n=87).
- The second step utilized early mature B (eBm5) cell examination, with patients split into training and testing sets.
Main Results:
- The second step assay demonstrated 88% specificity for OIS detection in both discovery and testing phases.
- The assay showed good diagnostic accuracy across different age groups and post-transplant durations.
- Patients testing positive for OIS had over a 12-fold increased risk (aHR 12.2) of adverse outcomes.
Conclusions:
- A sequential cell-based assay examining monocyte and eBm5 cell responses to EBV peptides can identify OIS in immunosuppressed patients.
- This assay offers high specificity and may be a valuable tool for optimizing immunotherapy.
- Early detection of OIS can potentially mitigate life-threatening adverse effects in transplant recipients.
