Noninvasive Monitoring of Human Cardiac Allograft Rejection

Reader, Jayne A.; Burke, Margaret; Counihan, Peter J.; Kirby, JA; Adams, Sue; Davies, M. J.; Pepper, John

doi:10.1097/00007890-199007000-00006

Cited by 20 publications

(8 citation statements)

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“…1). These results are in agreement with those of Herzog et al [2] but not with those of Reader et al [8], and with previous studies reporting that monitoring of peripheral bloodidoes not give information about intragraft events during rejection…”

Section: Resultssupporting

confidence: 93%

“…[S] suggested the clinical value of limiting dilution analysis of PBL which is a sensitive and quantitative method for measuring the frequency of donor-reactive CTL. Reader et al [8] found in a few cases a relationship between donor CTLpf and the immunological status of the graft. In samples taken on the day of transplantation and those obtained between 3 months and 3 years after transplantation.…”

Section: No Difference Was'observed Between Donor-specific Ctlpf Of Imentioning

confidence: 99%

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Long-term survival of heart grafts in the presence of donor-pecific cytotoxic T-cell precursors (CTLp) in the peripheral blood

et al. 1994

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To monitor their immunological status we determined donor and third-party-specific cytotoxic T-cell precursor frequencies (CTLpf) in the peripheral blood of 15 heart transplant recipients. PBL samples were obtained at different time points before and after transplantation. Donor-specific CTLpf and third-party-specific CTLpf were within the same range for all samples (1-1489/10(6) cells). The donor-specific CTLpf were not different between patients who had never had an acute rejection (AR) and patients who had an acute rejection as diagnosed by endomyocardial biopsy (EMB). No difference was observed between donor-specific CTLpf of samples taken on the day of transplantation and those obtained between 3 months and 3 years after transplantation. There was also no relationship between the donor-specific CTLpf in the PBL and the culturing success of lymphocytes from EMB taken at the same time. CTLpf were in the same range both when cultures could be propagated from the graft and when no cells grew out. We conclude that long-term graft survival is possible in the presence of CTLpf in peripheral blood.

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Section: Resultssupporting

confidence: 93%

Section: No Difference Was'observed Between Donor-specific Ctlpf Of Imentioning

confidence: 99%

Long-term survival of heart grafts in the presence of donor-pecific cytotoxic T-cell precursors (CTLp) in the peripheral blood

et al. 1994

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“…cCTL are not detectable using the present approach. Reader et al [25] suggested quantification of donor-reactive CTL in blood by means of LDA techniques as a useful tool for non-invasive rejection monitoring in cardiac transplants. An increase in the donor reactiveCTL frequency in the blood was associated with signs of rejection in the graft.…”

Section: Discussionmentioning

confidence: 99%

Acute rejection in heart transplant patients is associated with the presence of committed donor-specific cytotoxic lymphocytes in the graft but not in the blood

Vaessen

Baan

Ouwehand³

et al. 1992

Clinical and Experimental Immunology

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SUMMARYTn ri(v»-aclivated, committed donor-specific cytotoxic lymphocytes (cCTL) can be propagated and expanded from endomyocardial biopsies (EM B) in I L-2-enriched medium especially during an acute rejection episode. We report hereourefforts to detect these cCTL by the same technique in peripheral blood at the moment of rejection and when no rejection was diagnosed. During or just before rejection, significantly less frequent (/*< 0-01) donor reactive cCTL were found in PBL samples (two out of 20) than in the simultaneously taken EMB samples (13 out of 19). Donor B-LCL and/or thirdparty B-LCL were lysed by 15 PBL samples. Inhibition studies revealed that this lysis was due to LAK-like cylotoxicity. The results show that peripheral blood does not reflect intra-graft events, which is probably the reason for the irreproducible results of diagnosis of rejection by monitoring immunological parameters in the peripheral blood.

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“…Several groups studied the relation between the level of donor-speci®c CTLp in PBL and acute rejection [6±9]. Reader et al [9] claimed a signi®cant increase of CTLp frequencies during acute rejection (AR), although CTLp frequencies did not always correlate with histological rejection in the individual patient. The relation between stable engraftment and the frequency of alloreactive CTL and HTL is not very clear [10±16].…”

Section: Introductionmentioning

confidence: 99%

T helper frequencies in peripheral blood reflect donor-directed reactivity in the graft after clinical heart transplantation

Vaessen¹,

Daane²,

Maat

et al. 1999

Clinical and Experimental Immunology

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SUMMARYWe describe the usefulness of a fast (48-h) limiting dilution assay (LDA) for the enumeration of human alloreactive helper T lymphocytes (HTL) in the peripheral blood, in relation to histologically de®ned rejection grades after heart transplantation. HTL frequencies (HTLf) in pretransplant samples varied from patient to patient, ranging from 106 to 625 HTL/10 6 peripheral blood mononuclear cells (PBMC). In the ®rst week after heart transplantation (HTx), when immunosuppression was instituted, HTLf were signi®cant lower (range 30±190 HTL/10 6 ). The level of HTL in the ®rst week after HTx when rejection grade was 0 or 1A (ISHLT score) was considered to be the baseline frequency. This frequency did not correlate with the number of subsequent rejection episodes. During rejection (grade 3), donor-speci®c HTLf were increased above their baseline frequencies (P 0´01). Expressed as percentage of baseline frequencies, HTLf increased signi®cantly during acute rejection (AR) compared with 1±2 weeks before rejection (P 0´003). The increase was speci®c, since viral infections did not result in a rise of donorspeci®c HTL, while also HTLf speci®c for third party HLA antigens were not elevated during rejection. Monitoring HTLf in peripheral blood with a shortened (48-h) assay may serve as a non-invasive method for detecting intragraft immunological reactivity. Demonstrating absence of donor-speci®c reactivity may limit the number of invasive endomyocardial biopsy (EMB) procedures and allow tapering of immunosuppressive treatment.

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Noninvasive Monitoring of Human Cardiac Allograft Rejection

Cited by 20 publications

References 0 publications

Long-term survival of heart grafts in the presence of donor-pecific cytotoxic T-cell precursors (CTLp) in the peripheral blood

Long-term survival of heart grafts in the presence of donor-pecific cytotoxic T-cell precursors (CTLp) in the peripheral blood

Acute rejection in heart transplant patients is associated with the presence of committed donor-specific cytotoxic lymphocytes in the graft but not in the blood

T helper frequencies in peripheral blood reflect donor-directed reactivity in the graft after clinical heart transplantation

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