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Functional Characterization of Regulatory Macrophages That Inhibit Graft-reactive Immunity
Published on: June 7, 2017
Polymorphonuclear leukocyte functions as predictive markers for infections after organ transplantation
1Institute of General and Experimental Pathology, Karl-Franzens University, Graz, Austria. egger@leukotec.com
Abstract:
Infectious complications are still a major cause of morbidity and mortality after organ transplantation, and early therapy would certainly reduce the risk associated with severe infections. We therefore investigated the significance of polymorphonuclear leukocyte (PMN) functional tests as predictive markers for infection in transplant patients under immunosuppressive therapy in a longitudinal study. In 41 patients, blood PMN migration and reactive oxygen species release, the blood levels of PMN elastase, malondialdehyde, neopterin, sICAM-1 and sVCAM-1, and urine neopterine were measured in 3- and 4-day intervals after liver-, kidney-, kidney-pancreas-, and heart and lung transplantation. PMN migration was determined in whole blood and estimated by the amount of PMNs to penetrate into a membrane filter upon FMLP stimulation. Three groups of patients were formed according to their postoperative course. Group I patients (n = 23) had no or only minor local infection, group II patients (n = 11) had infections with distinct systemic involvement, and group III patients (n = 7) developed sepsis. A first elastase-level of over 100 mg/L after surgery, followed by a drop in the amount of blood PMNs ready to migrate, on FMLP stimulation, to below 12 %, turned out to be a marker for impending infection, whereas all other parameters tested were not predictive. In six of seven group III patients, this marker became positive (sensitivity 85.7 %) up to 15 days before clinical manifestation of sepsis. In group I (largely uneventful recovery) only one of 23 patients was positive (specificity 95.6 % ), whereas group II patients were in between (4 of 11 positive). By this method it seems possible to diagnose severe infections in the pre-clinical phase, which may help prevent them if treatment is begun promptly.
Insights
A new predictive marker for post-transplant infections has been identified. Elevated elastase levels followed by decreased polymorphonuclear leukocyte (PMN) migration can predict sepsis up to 15 days before clinical symptoms appear.
Area of Science:
- Transplant Surgery
- Infectious Diseases
- Immunology
Background:
- Infectious complications are a primary cause of morbidity and mortality in organ transplant recipients.
- Early detection and treatment of infections are crucial to reduce transplant-related risks.
Purpose of the Study:
- To investigate the predictive value of polymorphonuclear leukocyte (PMN) functional tests for detecting infections in transplant patients.
- To identify early markers for impending infections in immunosuppressed patients.
Main Methods:
- A longitudinal study involving 41 organ transplant patients (liver, kidney, kidney-pancreas, heart, lung).
- Measurement of PMN migration, reactive oxygen species release, PMN elastase, malondialdehyde, neopterin, sICAM-1, sVCAM-1, and urine neopterin at regular intervals post-transplant.
- Classification of patients into three groups based on postoperative infectious complications: no/minor infection, systemic infection, and sepsis.
Main Results:
- An elevated elastase level (>100 mg/L) post-surgery, followed by a decrease in PMN migration (<12%) upon FMLP stimulation, emerged as a significant predictive marker for infection.
- This marker showed high sensitivity (85.7%) in predicting sepsis, detecting it up to 15 days before clinical manifestation in 6 out of 7 sepsis patients.
- The marker demonstrated high specificity (95.6%) with only one patient in the uneventful recovery group testing positive.
Conclusions:
- The combined measurement of post-operative elastase levels and PMN migration function can serve as a valuable pre-clinical diagnostic tool for severe infections in transplant patients.
- Early detection of impending infections through this method may enable prompt therapeutic intervention, potentially preventing severe outcomes.
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