Cytomegalovirus Antigenemia as a Useful Marker of Symptomatic Cytomegalovirus Infection After Renal Transplantation—a Report of 130 Consecutive Patients

Berg, A. P. van den; Bij, W. van der; Son, Willem J. van; Anema, Jetske; Giessen, M. van der; Schirm, J; Tegzess, A. M.

doi:10.1097/00007890-198912000-00019

Cited by 175 publications

(90 citation statements)

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“…A sensitive, specific and rapid assay for early diagnosis and subsequent monitoring of an active HCMV infection has been based on these findings (HCMV antigenaemia assay;van der Bij et al, 1988a, b). The number of HCMV pp65-positive cells has been shown to correlate with disease activity (van den Berg et al, 1989(van den Berg et al, , 1991The et al, 1990) and the results obtained in several patient groups have since demonstrated the usefulness of this assay (Boland et al, 1990;Gerna et al, 1990;Boeckh et al, 1992;Erice et al, 1992;Ehrnst et al, 1993;Landini, 1993).…”

Section: Introductionmentioning

confidence: 99%

Presence of human cytomegalovirus (HCMV) immediate early mRNA but not ppUL83 (lower matrix protein pp65) mRNA in polymorphonuclear and mononuclear leukocytes during active HCMV infection

Grefte

Harmsen²,

Giessen³

et al. 1994

Journal of General Virology

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During an active human cytomegalovirus (HCMV) infection, leukocytes harbouring the HCMV lower matrix protein pp65 (ppUL83) are present in the peripheral blood and can be detected with the HCMV antigenaemia assay. In the present study, it was investigated whether the presence of pp65 in these cells was due to transcription of the virus genome or might be the result of uptake of this viral protein. Peripheral blood leukocytes of transplant recipients and AIDS patients with an active HCMV infection were investigated for the presence of HCMV immediate early (IE) antigen and pp65 using well characterized monoclonal antibodies, and for the presence of the corresponding mRNAs using non-radioactive in situ hybridization. Both mononuclear and polymorphonuclear cells were found to contain IE antigen and pp65. However, only mRNAs encoding IE antigen were found in these cells, whereas mRNAs encoding pp65 were not detected. In contrast, both IE antigen and pp65, as well as their corresponding mRNAs, were detected in the circulating late-stage HCMV-infected endothelial cells that were also present in the leukocyte fractions. These findings demonstrate that a restricted viral gene expression (transcription of IE genes) does occur in mononuclear and polymorphonuclear leukocytes. However, the abundant presence of the early antigen pp65 without detectable presence of the corresponding mRNA in these cells strongly indicates uptake of this protein by the phagocytic leukocytes, rather than de novo synthesis.

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Section: Introductionmentioning

confidence: 99%

Presence of human cytomegalovirus (HCMV) immediate early mRNA but not ppUL83 (lower matrix protein pp65) mRNA in polymorphonuclear and mononuclear leukocytes during active HCMV infection

Grefte

Harmsen²,

Giessen³

et al. 1994

Journal of General Virology

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“…The patients were observed for at least 3 months except in cases of graft loss or death. A total of 343 blood samples, with an average of 10 per recipient (range [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20], and 282 urine samples, with an average of 8 (range 1-13), were obtained from the 34 renal transplant recipients for analysis. A lung biopsy was also obtained from one patient.…”

Section: Study Populationmentioning

confidence: 99%

“…The patients were divided into two groups, those having symptomatic CMV infection and those having asymptomatic CMV infection, according to the method of Van der Berg et al (8), with some modifications. Briefly, the symptomatic CMV-infected patients were characterized by the presence of viral DNA detected in at least 2 consecutive samples of peripheral blood leukocytes (PBLs) or urine, and unexplained fever (>37.5 o C) for at least 3 days, in combination with at least one of the following features: arthralgia, leukopenia (<3 x 10 9 /l), thrombocytopenia (150 x 10 9 /l), liver enzyme elevation (ALT >50 U/l), pneumonitis or gastrointestinal ulceration without other causes.…”

Section: Study Populationmentioning

confidence: 99%

Cytomegalovirus infection in renal transplant recipients diagnosed by nested-PCR

Aquino

Figueiredo

2001

Braz J Med Biol Res

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A prospective study of cytomegalovirus (CMV) infection was carried out on 34 renal transplant recipients managed at a General Hospital in Ribeirão Preto, SP, Brazil. Serologic tests showed that all patients were infected with CMV before renal transplantation. Two nested-PCR techniques with primers that recognize sequences of the glycoprotein B (gB) and H (gH) genes were used for CMV detection in blood and urine samples during the post-transplantation period. CMV was detected more frequently in blood samples than in urine samples (P<0.001). Thirty-three patients had CMV detected at least once in blood and/or urine samples. Seven of these patients (21.2%) were diagnosed as having symptomatic CMV infection and showed a worse clinical outcome, with a higher death rate (P = 0.03). No association between CMV viremia and graft rejection was observed. Nested-PCR was not useful to identify patients at risk for symptomatic CMV infection since only 21.2% of the patients with CMV infection were symptomatic.

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“…The latter group of patients bears an added degree of risk in that CMV infection (either primary or reinfection) can be transmitted through the transplanted organ. For transplant recipients, the factors that influence the incidence and severity of CMV infection are the pretransplant level of CMV immunity, the source of infection, and the degree of immunosuppression ( 1). In addition to the direct complications attributable to CMV infection, the virus has been found to have modulating effects on the immune system ofthe infected individual (2).…”

mentioning

confidence: 99%

“…In addition to the direct complications attributable to CMV infection, the virus has been found to have modulating effects on the immune system ofthe infected individual (2). In some instances, CMV infection can result in generalized immunosuppression that predisposes the patient to secondary infection with other opportunistic pathogens ( 1,3). In contrast to these immunosuppressive effects of CMV infection, other evidence suggests that CMV infection can in fact induce or accelerate the rejection of an allograft (4).…”

mentioning

confidence: 99%

Accelerated rejection of murine cardiac allografts by murine cytomegalovirus-infected recipients. Lack of haplotype specificity.

et al. 1993

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Clinical studies have revealed a correlation between cytomegalovirus (CMV) infection and acute allograft rejection. Likewise, for a murine model we observed that C3H (H-2k) recipients infected with murine CMV (MCMV) rejected BALB/c (H-2") cardiac allografts earlier than uninfected recipients (6.9±0.1 d compared with 8.1±0.6 d; P < 0.001). It has been hypothesized that MCMV epitopes crossreact with alloantigens and in this manner induce rejection. However, we also demonstrated that MCMV caused accelerated rejection in the reverse combination (C3H heart engrafted to BALB/c recipient; 7.2±0.3 and 9.4±0.4 d for infected and control animals, respectively; P < 0.001 ) and accelerated rejection of grafts of a third, unrelated haplotype (C57BI/6; H-2b; 8.0±0.7 d compared with 10.1±0.6 for infected and control C3H recipients, respectively; P < 0.03). Ultraviolet (UV) inactivation of MCMV before administration to the graft recipient abrogated the ability to induce rapid rejection. Activated T lymphocytes were present in grafts from infected recipients 2 d before control recipients (P < 0.02) and, at the time of graft rejection, were almost exclusively CD8+ for both infected and control recipients. Thus, MCMV accelerated rejection appears not to result from crossreaction between MCMV epitopes and MHC products. The failure of UV-inactivated virus to accelerate rejection and the high proportion of CD8+ T cells recovered from all rejected grafts suggest that the class I pathway of antigen presentation may be important in the induction of early rejection. (J. Clin. Invest. 1993.91:2602-2608

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Cytomegalovirus Antigenemia as a Useful Marker of Symptomatic Cytomegalovirus Infection After Renal Transplantation—a Report of 130 Consecutive Patients

Cited by 175 publications

References 0 publications

Presence of human cytomegalovirus (HCMV) immediate early mRNA but not ppUL83 (lower matrix protein pp65) mRNA in polymorphonuclear and mononuclear leukocytes during active HCMV infection

Presence of human cytomegalovirus (HCMV) immediate early mRNA but not ppUL83 (lower matrix protein pp65) mRNA in polymorphonuclear and mononuclear leukocytes during active HCMV infection

Cytomegalovirus infection in renal transplant recipients diagnosed by nested-PCR

Accelerated rejection of murine cardiac allografts by murine cytomegalovirus-infected recipients. Lack of haplotype specificity.

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