The Correlation Between Symptomatic CMV Infection and CMV Antigenemia in Heart Allograft Recipients

Koskinen, Petri; Nieminen, Markku S.; Mattila, S; Häyry, P; Lautenschlager, Irmeli

doi:10.1097/00007890-199303000-00017

Cited by 61 publications

(32 citation statements)

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“…The viremic phase of infection was monitored by the antigenemia assay, which detects the presence of the viral protein pp65 in the nucleus of polymorphonuclear leukocytes and is an important indicator of CMV dissemination in the blood of immunocompromised patients [van den Berg et al, 1989;Ehrnst et al, 1993;Koskinen et al, 1993]. Virions and most viral material detected in polymorphonuclear leukocytes are not the result of a complete viral replication process occurring in these cells but are the result of a direct transmission of virus from CMV-infected endothelial cells to polymorphonuclear leukocytes through a cellto-cell contact Grundy et al, 1998;Gerna et al, 2000].…”

Section: Discussionmentioning

confidence: 99%

Autoantibody appearance in cytomegalovirus‐infected liver transplant recipients: Correlation with antigenemia

Varani

Muratori

Ruvo

et al. 2001

Journal of Medical Virology

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The presence of anti-endothelial cells (AECA), smooth muscle (SMA), antinuclear (ANA) and antimitochondrial (AMA) autoantibodies, and liver/kidney microsomal antibody type 1 (LKM1) was investigated retrospectively in sera of liver transplant patients and correlated with cytomegalovirus (CMV) infection as determined by the antigenemia test and with the appearance of acute or chronic allograft rejection. Indirect immunofluorescence analysis was carried out in sequential sera from 40 liver transplant patients. Ten out of 23 antigenemia-positive and none of the antigenemia-negative patients developed serum autoantibodies (P = 0.002, Fisher's exact test). Anti-endothelial cell autoantibodies were found in nine cases and SMA in four patients. Antinuclear antibodies were detected in one otherwise autoantibody-negative patient. All but one case of autoantibody positivity were observed in the high antigenemia group (P < 0.0001, Fisher's exact test). In all but one case, autoantibodies were detected in blood during the antigenemia phase and in most cases in coincidence with or after the antigenemia peak. Even though a statistically significant correlation was not found between autoantibody production and the development of acute or chronic allograft rejection, proportionally more acute rejection cases were observed in the autoantibody-positive than in the autoantibody-negative group. It has been speculated that CMV-induced endothelial damage may be a potent antigenic stimulus, which leads to the production of anti-endothelial cells autoantibodies. Anti-endothelial cell autoantibodies may represent not only a marker of cell injury but also contribute to the progression of the inflammatory response leading to the exposure of tissue-privileged self antigens and the induction of other autoantibodies such as SMA.

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Section: Discussionmentioning

confidence: 99%

Autoantibody appearance in cytomegalovirus‐infected liver transplant recipients: Correlation with antigenemia

Varani

Muratori

Ruvo

et al. 2001

Journal of Medical Virology

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“…The standard CMV pp65 antigenemia assay was performed in parallel (13,22,24). The leukocytes from peripheral blood specimens were isolated and cytocentrifuged onto microscope slides.…”

Section: Methodsmentioning

confidence: 99%

Monitoring of Viral Load by Quantitative Plasma PCR during Active Cytomegalovirus Infection of Individual Liver Transplant Patients

Piiparinen¹,

Höckerstedt

Lappalainen³

et al. 2002

J Clin Microbiol

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A quantitative PCR test, the Cobas Amplicor CMV Monitor, was used for the monitoring of viral load in the peripheral blood of 27 individual liver transplant patients and correlated with cytomegalovirus (CMV) pp65 antigenemia. Altogether, 243 specimens were analyzed. During the first 3 months, 20 patients showed PCR positivity which correlated with pp65 antigenemia. Of those, 13 patients developed symptomatic CMV infection 27 to 52 days after transplantation, with a significantly higher peak viral load in PCR and in pp65 assay compared with the seven asymptomatic infections (median 10,200 versus 2,240 copies/ml, P < 0.05, and median 100 versus 30 pp65-positive cells/50,000 leukocytes, P < 0.01). Five were primary infections of D؉/R؊ cases (donor CMV seropositive and recipient seronegative) and demonstrated, except in one case, a high peak viral load (>10,000 copies/ml; range, 10,200 to 21,600 copies, and >50 positive cells, range, 50 to 800 cells). The peak viral loads of the six D؉/R؉ patients with symptomatic infection varied widely (range, 2,290 to 126,000 copies and 50 to 300 positive cells). Two D؊/R؉ patients developed symptomatic infection with a lower viral load (range, 1,120 to 6,510 copies and 25 to 100 positive cells). All symptomatic infections were successfully treated with ganciclovir. The asymptomatic infections all in D؉/R؉ patients with low copy numbers (<5,500 copies) were monitored until CMV disappeared. One of the seven PCR-negative patients had one sample with low antigenemia, but the subsequent specimens were all negative. The time-related correlation of the two methods was also good. In summary, quantitative PCR could equally well be used as the CMV pp65 assay for the monitoring of viral load in individual transplant patients.Cytomegalovirus (CMV) infection is a common complication after liver transplantation. A variety of clinical manifestations of CMV, such as fever, leukopenia, thrombocytopenia, colitis, pneumonia, and hepatitis, have been described (16). Immunosuppressed organ transplant patients are usually frequently monitored for CMV and treated with antiviral agents. The antiviral treatment is based on the clinical symptoms and/or rapid laboratory diagnosis. Also, preemptive therapy, which is commonly used to prevent the development of CMV disease after transplantation, is based on monitoring the viral load of the patients (5,6,15,20).For more than 10 years, the CMV-pp65 antigenemia assay has been the most commonly used method for monitoring the appearance of CMV infection in transplant patients (2,8,22,25). The antigenemia test is quantitative and can also be used to assess viral load and to monitor the response to antiviral treatment. Although there have been attempts to standardize the assay (8, 23), the great variety of in-house and commercial modifications of the method make it difficult to compare the results and run clinical trials based on this technique. Quantitative PCR techniques, which are easy to standardize, are less laborious for laboratory personnel, and can be autom...

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“…Candidate laboratory tests include molecular assays that detect CMV DNA or RNA, antigenemia tests, and rapid viral cultures (2,33,91,163,239,297,335,336,351,464,474). It becomes imperative that the test chosen not only detect the presence of CMV sufficiently in advance of onset of symptoms, but also predict subsequent CMV disease and the need for antiviral therapy.…”

Section: Preemptive Prophylaxismentioning

confidence: 99%

“…Test positivity may precede CMV disease onset by up to 14 days (107,117,458,466,469), allowing for timely intervention. In cardiac transplant recipients, antigenemia is 83% sensitive as an early marker for the future development of symptomatic CMV infection but precedes the onset of overt disease by only 5 days (239). In one study, preemptive treatment with ganciclovir based on antigenemia reduced the incidence of disease in lung and heart transplant patients while omitting unnecessary antiviral prophylaxis in those who were CMV antigen negative (110).…”

Section: Preemptive Prophylaxismentioning

confidence: 99%

New Strategies for Prevention and Therapy of Cytomegalovirus Infection and Disease in Solid-Organ Transplant Recipients

Sia¹,

Patel²

2000

Clinical Microbiology Reviews

220

181

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The Correlation Between Symptomatic CMV Infection and CMV Antigenemia in Heart Allograft Recipients

Cited by 61 publications

References 0 publications

Autoantibody appearance in cytomegalovirus‐infected liver transplant recipients: Correlation with antigenemia

Autoantibody appearance in cytomegalovirus‐infected liver transplant recipients: Correlation with antigenemia

Monitoring of Viral Load by Quantitative Plasma PCR during Active Cytomegalovirus Infection of Individual Liver Transplant Patients

New Strategies for Prevention and Therapy of Cytomegalovirus Infection and Disease in Solid-Organ Transplant Recipients

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