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Immune Monitoring Assay for Extracorporeal Photopheresis Treatment Optimization After Heart Transplantation

Background: Extracorporeal photopheresis (ECP) induces immunological changes that
lead to a reduced risk of transplant rejection. The aim of the present study was to
determine optimum conditions for ECP treatment by analyzing a variety of toleranceinducing
immune cells to optimize the treatment.
Methods: Ten ECP treatments were applied to each of 17 heart-transplant patients from
month 3 to month 9 post-HTx. Blood samples were taken at baseline, three times during
treatment, and four months after the last ECP treatment. The abundance of subsets of
tolerance-inducing regulatory T cells (Tregs) and dendritic cells (DCs) in the samples was
determined by flow cytometry. A multivariate statistical model describing the
immunological status of rejection-free heart transplanted patients was used to visualize
the patient-specific immunological improvement induced by ECP.
Results: All BDCA+ DC subsets (BDCA1+ DCs: p < 0.01, BDCA2+ DCs: p < 0.01,
BDCA3+ DCs: p < 0.01, BDCA4+ DCs: p < 0.01) as well as total Tregs (p < 0.01) and
CD39+ Tregs (p < 0.01) increased during ECP treatment, while CD62L+ Tregs decreased
(p < 0.01). The cell surface expression level of BDCA1 (p < 0.01) and BDCA4 (p < 0.01) on
DCs as well as of CD120b (p < 0.01) on Tregs increased during the study period, while
CD62L expression on Tregs decreased significantly (p = 0.04). The cell surface expression
level of BDCA2 (p = 0.47) and BDCA3 (p = 0.22) on DCs as well as of CD39 (p = 0.14) and
CD147 (p = 0.08) on Tregs remained constant during the study period. A cluster analysis
showed that ECP treatment led to a sustained immunological improvement.
Conclusions: We developed an immune monitoring assay for ECP treatment after heart
transplantation by analyzing changes in tolerance-inducing immune cells. This assay
allowed differentiation of patients who did and did not show immunological improvement.
Based on these results, we propose classification criteria that may allow optimization of
the duration of ECP treatment.

Identiferoai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:84297
Date24 March 2023
CreatorsDieterlen, Maja-Theresa, Klaeske, Kristin, Bernhardt, Alexander A., Borger, Michael A., Klein, Sara, Garbade, Jens, Lehmann, Sven, Ayuk, Francis Ayuketang, Reichenspurner, Herrmann, Barten, Markus J.
PublisherFrontiers Research Foundation
Source SetsHochschulschriftenserver (HSSS) der SLUB Dresden
LanguageEnglish
Detected LanguageEnglish
Typeinfo:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text
Rightsinfo:eu-repo/semantics/openAccess
Relation1664-3224, 676175

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