Cytomegalovirus DNA Load Patterns Developing After Lung Transplantation Are Significantly Correlated With Long-Term Patient Survival

Kerschner, Heidrun; Jaksch, Péter; Karigl, Günther; Popow‐Kraupp, Theresia; Klepetko, Walter; Puchhammer‐Stöckl, Elisabeth

doi:10.1097/tp.0b013e3181a60b4e

Cited by 27 publications

(27 citation statements)

References 47 publications

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“…High-level HCMV DNAemia is linked to the development of HCMV disease and can even trigger allograft rejection (7)(8)(9)(10)(11)(12)(13). Therefore, a deeper understanding is required of how the level of HCMV replication is affected by the immune system, in particular by cytotoxic CD8+ T cells, which are essential for containing HCMV (14)(15)(16)(17)(18)(19)(20)(21)(22)(23).…”

Section: Discussionmentioning

confidence: 99%

“…From these 67 patients, 1121 plasma samples with a mean of 17 samples per patient (range: 8-43) were collected during the follow-up at a mean interval of 25.6 days (range: 2-95), and HCMV DNA loads were measured. In parallel, a total of 758 heparinized whole-blood samples with a mean of 11.5 serial samples per patient (range: [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] were acquired prospectively at a mean interval of 31.7 days (range: 4-111) and were tested for HCMV-specific CD8+ T cell responses using the QuantiFERON R -CMV assay (Cellestis GmbH, a QIAGEN company). Of these, 598 samples (78.9%) gave a determinate result.…”

Section: Prospective Recruitment Of Patients and Acquisition Of Seriamentioning

confidence: 99%

“…HCMV DNAemia may also trigger chronic inflammatory processes that have been associated with bronchiolitis obliterans syndrome, and there is evidence that multiple and prolonged episodes of HCMV DNAemia significantly reduce long-term survival rates (10)(11)(12)(13). Although measurement of plasma HCMV DNA levels is a routine tool in the monitoring of LuTRs, the functional mechanisms that lead to hematogenous HCMV dissemination are not entirely understood.…”

Section: Introductionmentioning

confidence: 99%

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Prospective Analysis of Human Cytomegalovirus DNAemia and Specific CD8+ T Cell Responses in Lung Transplant Recipients

Weseslindtner

Kerschner

Steinacher

et al. 2012

American Journal of Transplantation

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In lung transplant recipients (LuTRs), human cytomegalovirus (HCMV) DNAemia may be associated with HCMV disease and reduced survival of the allograft. Because T cells are essential for controlling HCMV replication, we investigated in this prospective study whether the kinetics of plasma HCMV DNA loads in LuTRs are associated with HCMV-specific CD8+ T cell responses, which were longitudinally assessed using a standardized assay. Sixty-seven LuTRs were monitored during the first year posttransplantation, with a mean of 17 HCMV DNA PCR quantifications and 11.5 CD8+ T cell tests performed per patient. HCMV-specific CD8+ T cell responses displayed variable kinetics in different patients, differed significantly before the onset of HCMV DNAemia in LuTRs who subsequently experienced episodes of DNAemia with high (>1000 copies/mL) and low plasma DNA levels (p = 0.0046, Fisher's exact test), and were absent before HCMV disease. In HCMV-seropositive LuTRs, highlevel DNAemia requiring preemptive therapy occurred more frequently when HCMV-specific CD8+ T cell responses fluctuated, were detected only after HCMV DNA detection, or remained undetectable (p = 0.0392, Fisher's exact test). Thus, our data indicate that HCMVspecific CD8+ T cells influence the magnitude of HCMV DNAemia episodes, and we propose that a standardized measurement of CD8+ T cell immunity might contribute to monitoring the immune status of LuTRs posttransplantation.

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Section: Discussionmentioning

confidence: 99%

Section: Prospective Recruitment Of Patients and Acquisition Of Seriamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prospective Analysis of Human Cytomegalovirus DNAemia and Specific CD8+ T Cell Responses in Lung Transplant Recipients

Weseslindtner

Kerschner

Steinacher

et al. 2012

American Journal of Transplantation

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“…The detection of CMV in BAL fluid may or may not be indicative of CMV pneumonia (68,73,(141)(142)(143)(144)(145). Shedding of CMV in saliva and respiratory secretions is not uncommon, and the demonstration of CMV DNA in these respiratory samples in the absence of compatible clinical signs and symptoms (or in the absence of biopsy confirmation) is of unclear significance and does not necessarily indicate CMV pneumonia (141).…”

Section: Nucleic Acid-based Methodsmentioning

confidence: 99%

“…CMV-infected patients are also more likely to develop Epstein-Barr virus infection with subsequent posttransplant lymphoproliferative disease (67). Finally, CMV has been associated with poorer long-term allograft and patient survival outcomes (57,68,69).…”

Section: Clinical Diseasementioning

confidence: 99%

Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

2013

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SUMMARY The negative impact of cytomegalovirus (CMV) infection on transplant outcomes warrants efforts toward improving its prevention, diagnosis, and treatment. During the last 2 decades, significant breakthroughs in diagnostic virology have facilitated remarkable improvements in CMV disease management. During this period, CMV nucleic acid amplification testing (NAT) evolved to become one of the most commonly performed tests in clinical virology laboratories. NAT provides a means for rapid and sensitive diagnosis of CMV infection in transplant recipients. Viral quantification also introduced several principles of CMV disease management. Specifically, viral load has been utilized (i) for prognostication of CMV disease, (ii) to guide preemptive therapy, (iii) to assess the efficacy of antiviral treatment, (iv) to guide the duration of treatment, and (v) to indicate the risk of clinical relapse or antiviral drug resistance. However, there remain important limitations that require further optimization, including the interassay variability in viral load reporting, which has limited the generation of standardized viral load thresholds for various clinical indications. The recent introduction of an international reference standard should advance the major goal of uniform viral load reporting and interpretation. However, it has also become apparent that other aspects of NAT should be standardized, including sample selection, nucleic acid extraction, amplification, detection, and calibration, among others. This review article synthesizes the vast amount of information on CMV NAT and provides a timely review of the clinical utility of viral load testing in the management of CMV in solid organ transplant recipients. Current limitations are highlighted, and avenues for further research are suggested to optimize the clinical application of NAT in the management of CMV after transplantation.

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Clinical characteristics and outcomes of pediatric patients with CMV DNA detection in bronchoalveolar lavage fluid

et al. 2016

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Cytomegalovirus DNA Load Patterns Developing After Lung Transplantation Are Significantly Correlated With Long-Term Patient Survival

Abstract: Active CMV replication that is not limited after one episode of CMV DNAemia leads to significantly decreased long-term survival after LuTX.

Cited by 27 publications

References 47 publications

Prospective Analysis of Human Cytomegalovirus DNAemia and Specific CD8+ T Cell Responses in Lung Transplant Recipients

Prospective Analysis of Human Cytomegalovirus DNAemia and Specific CD8+ T Cell Responses in Lung Transplant Recipients

Clinical Utility of Viral Load in Management of Cytomegalovirus Infection after Solid Organ Transplantation

Clinical characteristics and outcomes of pediatric patients with CMV DNA detection in bronchoalveolar lavage fluid

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