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Inverse Monocytic Subset Profile in Blood and Tissue During Heart Transplant Rejection

T. van den Bosch,1 M. Kraaij,1 K. Caliskan,2 A. Constantinescu,2 O. Manintveld,2 P. Leenen,3 C. Baan,1 M. van Groningen,4 A. Rowshani.1

1Department of Internal Medicine, Section Nephrology and Transplantation, Erasmus Medical Center, Rotterdam, Netherlands
2Department of Cardiology, Erasmus Medical Center, Rotterdam, Netherlands
3Department of Immunology, Erasmus Medical Center, Rotterdam, Netherlands
4Department of Pathology, Erasmus Medical Center, Rotterdam, Netherlands.

Meeting: 2015 American Transplant Congress

Abstract number: A6

Keywords: Endomyocardial biopsy, Heart transplant patients, Image analysis, Inflammation

Session Information

Session Name: Poster Session A: Acute Allograft Rejection

Session Type: Poster Session

Date: Saturday, May 2, 2015

Session Time: 5:30pm-7:30pm

 Presentation Time: 5:30pm-7:30pm

Location: Exhibit Hall E

Introduction: Increased monocytic infiltration of heart transplant tissue is documented during acute rejection. It is still unclear how changes in circulating monocyte pool relate to counterpart alterations of monocyte-macrophage infiltrates on tissue level. We aimed to establish blood and tissue monocyte/macrophage profiles using serial blood samples and endomyocardial biopsies in 10 heart transplant recipients experiencing rejection in comparison to time points prior to rejection intra-individually. Blood profiles of heart transplant recipients were compared with 33 healthy individuals using a cross-sectional approach.

Method: Flow cytometric expression of co-stimulatory and migration-related molecules; HLA-DR, CD40, CD80, and CD54 were studied on different monocyte subsets. TNF-α, IFN-γ, IL-1β, IL-6, IL-10, IL-12 production capacity of monocytes were measured after LPS stimulation. Using immunohistochemistry we studied expression of CD14, CD16, CD56, CD68, CD80, CD163 in endomyocardial biopsies.

Results: Increased classical CD14++CD16- monocytes and simultaneously decreased fractions of intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes signify the subset composition of circulating monocytes in heart transplant recipients compared to healthy individuals. However, rejection was reflected by significantly increased expression of CD54 and HLA-DR within the CD16+ monocyte pool indicative of a higher antigen presentation potential and migration capacity. Cytokine production potential was consistently high and independent of rejection. Significantly more CD16+ monocytes were found in rejecting endomyocardial biopsies compared to non-rejection. Significantly more CD68+CD163+ M2 macrophages were documented during rejection parallel to this increase in intra-graft CD16+ monocyte infiltration.

Conclusions: Our data show inverse monocytic subset profile in blood and tissue during human heart transplant rejection with a simultaneous predominance of M2 anti-inflammatory macrophages.

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To cite this abstract in AMA style:

Bosch Tvanden, Kraaij M, Caliskan K, Constantinescu A, Manintveld O, Leenen P, Baan C, Groningen Mvan, Rowshani A. Inverse Monocytic Subset Profile in Blood and Tissue During Heart Transplant Rejection [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/inverse-monocytic-subset-profile-in-blood-and-tissue-during-heart-transplant-rejection/. Accessed May 19, 2025.

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