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Heart transplantation

Tuesday September 24, 2024 - 10:40 to 12:10

Room: Maçka

326.5 Relationship between tissue IgG plasma cells and serum donor-specific antibodies in cardiac allograft recipients with repeated antibody-mediated rejection

Gonca Ozgun, Turkey

Department of Pathology
Baskent University

Abstract

Relationship between tissue IgG plasma cells and serum donor-specific antibodies in cardiac allograft recipients with repeated antibody-mediated rejection

Aysen Terzi1, Bilkay Basturk2, B. Handan Ozdemir1, Miray Kavuzlu1, Gonca Ozgun1, Imge Terzi1, Mohammad Amin Ghaffari1, Atilla Sezgin3.

1Department of Pathology, Baskent University, Ankara, Turkey; 2Department of Immunology, Baskent University, Ankara, Turkey; 3Department of Cardiovascular Surgery, Baskent University, Ankara, Turkey

Introduction: Due to unclear boundaries, diagnosing antibody-mediated rejection (ABMR) in cardiac allografts poses challenges for pathologists and clinicians. Timely and accurately diagnosing ABMR's immunological and histopathological features is crucial for effective treatment and preventing adverse outcomes. Our study aims to elucidate the role of plasma cells and IgG expression in ABMR pathogenesis and identify potential markers in histopathological and immunological assessments.
Methods: The study included 91 endomyocardial biopsies (EMBs) obtained from 19 recipients. These patients experienced recurrent episodes of ABMR. Immunohistochemically CD138, IgG, IgG1, IgG3, C4d, and CD68 were evaluated in 91 EMBs. Positive cells were quantified under high magnification, considering all inflammatory cells in the myocardium interstitium, subendocardium, and capillaries. The ratio of positive cells to all inflammatory cells in the field was calculated, with a threshold value set at 10%. Additionally, positivity rates of endothelial cells (EC) were recorded using the same approach.
Results: Among the 91 biopsies, 20 (22%) exhibited mild ABMR-1, 16 (17.6%) showed ABMR-2 or ABMR-3, 32 (35.2%) presented mixed rejection (ABMR and TCMR), 7 (7.7%) displayed TCMR, and 16 (17.6%) showed no rejection. The proportion of CD138-positive plasma cells and IgG, IgG1, or IgG3-positive inflammatory cells was associated significantly with C4d positivity (p<0.01), C4d expression grade (p<0.01), DSA positivity (p<0.01), and MFI values (p<0.05). Positivity rates in ECs also paralleled the rates of the positive inflammatory cells in the allograft, and their distribution among diagnostic groups showed significant differences (p<0.01). The cut-off point of plasma cells and IgG, IgG1, and IgG3-positive cells was one cell. Only one positive cell for CD138, IgG, IgG1, or IgG3  had a significant association with the positivity of both C4d and DSA, thus the diagnosis of ABMR (P<0.01). In patient-based analyses, considering rejection episodes and treatment, the presence and the density of IgG1 and IgG3 positive cells in the allograft showed a close correlation with the DSA MFI levels (p<0.01). Especially when treatment-related DSA results are considered, IgG1-positive cells stand out as a more sensitive (p<0.05) and IgG3-positive cells as a more specific (p<0.01) possible DSA marker.
Conclusion: Especially in AMR-1 cases where C4d and CD68 findings are diagnostically borderline and DSA status is unknown, monitoring IgG, IgG1, or IgG3-positive cells in the allograft and the presence of plasma cells may help to make an accurate diagnosis. IgG1 and IgG3-positive cells in the EMBs appear especially related to DSA positivity, and the number of positive cells increases and decreases with the amount of MFI levels. We suggested investigating these immune markers in larger patient-based groups as two potential diagnostic markers may provide new insights into evaluating and treating heart transplants.

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