Fulminant Acute Cellular Rejection With Negative Findings on Endomyocardial Biopsy

Bhalodolia, Rajeshkumar; Cortese, Cherise; Graham, Michael; Hauptman, Paul J.

doi:10.1016/j.healun.2006.04.002

Cited by 18 publications

(14 citation statements)

References 15 publications

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“…Allograft biopsies are invasive, and because rejection is a diffuse process, multiple biopsies are often required . Allograft rejection is often assessed using clinical indices of organ function , but these usually reflect rather than predict organ damage. Detection of increased alloreactivity before organ dysfunction develops could provide an enhanced opportunity for therapeutic intervention.…”

Section: Resultsmentioning

confidence: 99%

Quantification of CD4+ T Cell Alloreactivity and Its Control by Regulatory T Cells Using Time-Lapse Microscopy and Immune Synapse Detection

Juvet

Sanderson

Hester

et al. 2016

American Journal of Transplantation

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Assays designed to select transplant recipients for immunosuppression withdrawal have met with limited success, perhaps because they measure events downstream of T cell–alloantigen interactions. Using in vitro time‐lapse microscopy in a mouse transplant model, we investigated whether transplant outcome would result in changes in the proportion of CD4+ T cells forming prolonged interactions with donor dendritic cells. By blocking CD4–MHC class II and CD28–B7 interactions, we defined immunologically relevant interactions as those ≥500 s. Using this threshold, T cell–dendritic cell (T‐DC) interactions were examined in rejection, tolerance and T cell control mediated by regulatory T cells. The frequency of T‐DC contacts ≥500 s increased with T cells from mice during acute rejection and decreased with T cells from mice rendered unresponsive to alloantigen. Regulatory T cells reduced prolonged T‐DC contacts. Importantly, this effect was replicated with human polyclonally expanded naturally occurring regulatory T cells, which we have previously shown can control rejection of human tissues in humanized mouse models. Finally, in a proof‐of‐concept translational context, we were able to visualize differential allogeneic immune synapse formation in polyclonal CD4+ T cells using high‐throughput imaging flow cytometry.

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Section: Resultsmentioning

confidence: 99%

Quantification of CD4+ T Cell Alloreactivity and Its Control by Regulatory T Cells Using Time-Lapse Microscopy and Immune Synapse Detection

Juvet

Sanderson

Hester

et al. 2016

American Journal of Transplantation

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“…Patients who experience AR grades 3A, 3B and 4 (revised grade 2R or 3R) within this time frame exhibit poor five-year survival as well as an increased risk of cardiac allograft vasculopathy 4, 5 despite intervention. Several studies have drawn attention to discordance between histological grade and graft function, particularly in settings where declining cardiac function and increasing mortality proceed independently of histological grade 6, 7 . These observations point to the need for greater understanding of underlying processes that may unveil alternative or complementary approaches for AR surveillance with the goal of accurate and early diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Identification and Classification of Acute Cardiac Rejection by Intragraft Transcriptional Profiling

Holweg

Potena²,

Luikart³

et al. 2011

Circulation

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Background Treatment of acute rejection (AR) in heart transplantation relies on histopathological grading of endomyocardial biopsies (EMB) according to International Society for Heart and Lung Transplantation (ISHLT) guidelines. Intragraft gene expression profiling may be a way to complement histological evaluation. Methods and results Transcriptional profiling was performed on 26 EMB and expression patterns were compared with the 1990 ISHLT AR grades. Importantly, transcriptional profiles from settings with an equivalent AR grade appeared the same. In addition, grade 0 profiles could not be distinguished from 1A and grade 3A profiles could not be distinguished from 3B. Comparing the AR groupings (0+1A, 1B, and 3A+3B), 0+1A showed more striking differences from 1B than from 3A+3B. When these findings were extrapolated to the 2005 revised guidelines, the combination of 1A and 1B into a single category (1R) appears to have brought together EMBs with different underlying processes that is not evident from histological evaluation. Grade 1B was associated with upregulated immune response genes, as one categorical distinction from grade 1A. Although, grade 1B was distinct from the clinically relevant AR grades 3A and 3B, all of these grades shared a small number of overlapping pathways consistent with common physiological underpinnings. Conclusion The gene expression similarities and differences identified here in different AR settings have the potential to revise the clinical perspective on acute graft rejection, pending the results of larger studies.

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“…This brings up the question of whether BNR should exist as a separate category of rejection or is merely a by-product of the problems inherent with endomyocardial biopsies. In one case study, sampling error or nonuniformity of histopathologic changes resulted in a falsenegative biopsy [5]. In this case study, a heart transplant recipient with repeatedly unremarkable endomyocardial biopsies and a negative evaluation for humoral rejection was found to have severe subepicardial myocyte necrosis with classic cellular rejection in the subsequent autopsy.…”

Section: Discussionmentioning

confidence: 79%

“…To minimize the risk of a false negative, multiple specimens (usually [3][4][5] are obtained from 3 different sites. Though rare, false negatives do exist either through sampling error, artifact, Quilty lesions, or pathology misread.…”

Section: Introductionmentioning

confidence: 99%

683 The Natural History of Biopsy Negative Rejection after Heart Transplantation

Patel¹,

Kittleson²,

Rafiei³

et al. 2012

The Journal of Heart and Lung Transplantation

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.Purpose. The most recent International Society for Heart and Lung Transplantation (ISHLT) biopsy scale classifies cellular and antibody-mediated rejections. However, there are cases with acute decline in left ventricular ejection fraction (LVEF ≤ 45%) but no evidence of rejection on biopsy. Characteristics and treatment response of this biopsy negative rejection (BNR) have yet to be elucidated. Methods. Between 2002 and 2012, we found 12 cases of BNR in 11 heart transplant patients as previously defined. One of the 11 patients was treated a second time for BNR. Characteristics and response to treatment were noted. Results. 12 cases (of 11 patients) were reviewed and 11 occurred during the first year after transplant. 8 cases without heart failure symptoms were treated with an oral corticosteroids bolus and taper or intravenous immunoglobulin. Four cases with heart failure symptoms were treated with thymoglobulin, intravenous immunoglobulin, and intravenous methylprednisolone followed by an oral corticosteroids bolus and taper. Overall, 7 cases resulted in return to normal left ventricular function within a mean of 14 ± 10 days from the initial biopsy. Conclusion. BNR includes cardiac dysfunction and can be a severe form of rejection. Characteristics of these cases of rejection are described with most cases responding to appropriate therapy.

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Fulminant Acute Cellular Rejection With Negative Findings on Endomyocardial Biopsy

Cited by 18 publications

References 15 publications

Quantification of CD4+ T Cell Alloreactivity and Its Control by Regulatory T Cells Using Time-Lapse Microscopy and Immune Synapse Detection

Quantification of CD4+ T Cell Alloreactivity and Its Control by Regulatory T Cells Using Time-Lapse Microscopy and Immune Synapse Detection

Identification and Classification of Acute Cardiac Rejection by Intragraft Transcriptional Profiling

683 The Natural History of Biopsy Negative Rejection after Heart Transplantation

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