Human cytomegalovirus and Epstein–Barr virus infections occurring early after transplantation are risk factors for antibody-mediated rejection in heart transplant recipients (original) (raw)
Related papers
International Immunopharmacology, 2009
We sought to determine whether quantitative assessment of anti-cytomegalovirus (CMV) antibodies could be useful to identify patients at risk of cytomegalovirus (CMV) disease after heart transplantation (HT). 75 patients who underwent HT at a single health care center were prospectively studied. Induction therapy included 2 doses of daclizumab and maintenance tacrolimus (n = 42) or cyclosporine (n = 29), mycophenolate mofetil and prednisone. All patients received prophylaxis with gancyclovir or valganciclovir. Anti-CMV intravenous immunoglobulin (CMV-IG) was added in high risk patients (CMV D+/R− serostatus). Serial determinations of anti-CMV antibodies, immunoglobulins (IgG, IgA, IgM) and IgG-subclasses were analysed. CMV infection was based on detection of the virus by antigenemia. CMV disease consisted of detection of signs or symptoms attributable to this microorganism. Ten patients (13.3%) developed CMV disease. Mean time of development of CMV disease was 3.4 ± 1.6 months. In Cox regression analysis, patients with low baseline anti-CMV titers (b 4.26 natural logarithm of titer, RH: 8.1, 95%CI: 1.93-34.1, p = 0.004) and recipients with 1-month post-HT IgG hypogammaglobulinemia (IgGb 500 mg/dl, RH: 4.49, 95%CI: 1.26-15.94, p = 0.02) were at higher risk of having CMV disease. Despite use of prophylactic CMV-IG, D+/R− patients showed significantly lower titers of anti-CMV antibodies at 7 d, 30 d and 90 d post HT as compared with HT recipients without infections. Four out of 6 of these patients developed late CMV disease. Monitoring of specific anti-CMV antibodies on the bedside warrants further evaluation as a potential tool to identify heart transplant recipients at higher risk of CMV disease.
Journal of Medical Virology, 1994
The relationship between cytomegalovirus KEY WORDS: cytomegalovirus, heart trans-(CMV) infection and cardiac allograft rejection is plantation, rejection, tissue bicontroversial, some authors reporting a signifiopsy, virus diagnosis cant association, others not, on the basis of the results of conventional virological diagnosis by culture or serology. This problem was reinvestigated in 88 patients using a semi-quantitative nest polymerase chain reaction (PCR) procedure for detecting CMV DNA in endomyocardial biopsy specimens. Significantly more positive biopsies were obtained from patients with moderate (grade 2; P = 0.02) or severe (grade 3a-4; P = 0.03) rejection than with no or mild (grade 0-1 b) rejection, whereas there was no significant association between rejection and CMV as diagnosed by virus isolation from urine, throat or blood, or by the detection of CMV-ISM.
Transplant Infectious Disease, 2011
Background. The objectives of this epidemiological, prospective study were to describe the characteristics of cytomegalovirus (CMV) infection in heart transplant (HT) recipients and to identify the variables that may in£uence the development of CMV viremia and CMV disease in these patients. Methods. HT recipients ! 18 years of age (n 5 199) were included in the study.Variables studied included CMV serostatus, immunosuppressive treatment, and administration of anti-CMV prophylaxis. Results. The mean age of the population was 52 years, and 84% were males. Immunosuppressive regimens were administered as induction therapy to 92.5% of patients; 88.5% of patients received calcineurin inhibitors as maintenance therapy. Anti-CMV treatment was given to 59% of 199 patients as prophylaxis (70%), preemptive therapy (10%), or to treat CMV infection (20%). Overall, 43% of patients had at least 1 positive viremia test. No patient with a high-risk serostatus (donor 1 / recipient À) receiving prophylaxis developed CMV syndrome, and only 2.5% of 199 patients developed CMV invasive disease. Multivariate analysis showed that having a positive donor CMV serostatus was associated with an increased risk of developing CMV viremia (Po0.012), while use of mammalian target of rapamycin (mTOR) inhibitors was associated with a decreased risk (P 5 0.005). Conclusions. In a population of HT recipients, the CMV infection rate was similar to that seen in previous studies, but the progression to overt CMVdisease was very low. Having a CMV-positive donor was identi¢ed as an independent risk factor for developing CMV viremia, while the use of mTOR inhibitors was protective against viremia.
Cytomegalovirus Infection in Heart-Transplant Recipients in a Central Region of Italy
European Journal of Inflammation, 2004
Cytomegalovirus (CMV) infection occurs very often after solid organ transplantation and is often a lifethreatening complication oflong-term immunosoppressive therapy. Actually it is unknown which type of drug is indicated to control the infection in immunocompromised patients. We studied 10 consecutive patients who had undergone heart-transplantation and in which CMV infection was the commonest posttransplant infectious disease. Our results suggest a careful monitoring of IgG seropositivity in heart transplant patients, especially when it is not possible to know the serum status of the donor.
Journal of Clinical Microbiology, 2012
HTXs at risk of infection. In this study, 10 CMV-seropositive (R ؉ ) pretransplant patients and 48 preemptively treated R ؉ HTXs were examined before and after 100 days posttransplant. Preemptive treatment is supposed to favor the immune recovery. CMV DNAemia and gamma interferon enzyme-linked immunosorbent spot (ELISPOT) assay were employed to assess the viremia and immune reconstitution. HTXs could be categorized into three groups characterized by high (>100), medium (50 to 100), and low (<50) spot levels. Early-identified high responders efficiently controlled the infection and also maintained high immunity levels after 100 days after transplant. No episodes of grade >2R rejection occurred in the high responders. Midresponders were identified as a group with heterogeneous trends of immune reconstitution. Low responders were 41% and 21% of HTXs before and after 100 days posttransplant, respectively. Low responders were associated with a higher incidence of infection. The effect of viremia on immune recovery was investigated: a statistically significant inverse correlation between magnitude of viremia and immune recovery emerged; in particular, each 10-fold increase in viremia (>4 log 10 DNAemia/ml) was associated with a 36% decrease of the ELISPOT assay spot levels. All episodes of high viremia (>4 log 10 DNAemia/ml) occurred from 1 to 60 days after transplant. Thus, the concomitant evaluation of viremia and CMV immune reconstitution has clinical utility in identifying HTXs at risk of infection and may represent a helpful guide in making therapeutic choices.
Diagnosis of cytomegalovirus infection in heart transplant recipients
Journal of Clinical Pathology, 1992
In a prospective study eight (47%) heart transplant recipients had recurrent cytomegalovirus (CMV) infection. Of these, five had received hearts from seropositive donors. Neither serology nor virus isolation from urine was reliably associated with clinical CMV infection, but a high CMV IgM index correlated with CMV infection.
Impact of cytomegalovirus serologic status on heart transplantation
Journal of Cardiac Surgery, 2020
Background: Cytomegalovirus (CMV) infection has been associated with increased risk of mortality, cardiac allograft vasculopathy, and de novo malignancy following heart transplantation in prior institutional reports. This study examines the impact of the recipient and donor CMV status on heart recipients in the United States. Methods: Adult heart transplant recipients were identified in the OPTN registry between 2005-2016. Recipients were stratified based on the recipient (R) and donor (D) CMV serologic status (+/−). The primary endpoint was survival 5-years after transplantation. The secondary endpoint was cardiac allograft vasculopathy 5-years after transplantation. Separate Cox proportional hazards regression models were developed to evaluate independent associations between CMV status and each of the study endpoints. Results: A total of 21 878 recipients met the inclusion criteria. The breakdown of study arms by CMV serologic status was R−/D− = 3412, R+/D− = 4939; R−/D+ = 5230, and R+/D+ = 8,297. Five-year survival estimates were similar across groups (77-79%). CMV status was associated with increased mortality at 5-years (23%-41% increased risk) which was most evident in the first 3 months. The use of valganciclovir was associated with decreased risk of mortality (HR 0.56; 95% CI, 0.52-0.60). The cumulative incidence of cardiac allograft vasculopathy (R−/D− = 31%, R+/D− = 30%, R−/D+ = 31%, and R+/D+ = 30%) was similar across groups. CONCLUSIONS: CMV seropositivity at the time of transplantation is associated with increased long-term risk of mortality. Chemoprophylaxis with antivirals seems to mitigate this risk. There was no association with an increased risk of allograft vasculopathy.
BMC infectious diseases, 2015
Cytomegalovirus (CMV) is associated with an increased risk of cardiac allograft vasculopathy (CAV), the major limiting factor for long-term survival after heart transplantation (HTx). The purpose of this study was to evaluate the impact of CMV infection during long-term follow-up after HTx. A retrospective, single-centre study analyzed 226 HTx recipients (mean age 45 ± 13 years, 78 % men) who underwent transplantation between January 1988 and December 2000. The incidence and risk factors for CMV infection during the first year after transplantation were studied. Risk factors for CAV were included in an analyses of CAV-free survival within 10 years post-transplant. The effect of CMV infection on the grade of CAV was analyzed. Survival to 10 years post-transplant was higher in patients with no CMV infection (69 %) compared with patients with CMV disease (55 %; p = 0.018) or asymptomatic CMV infection (54 %; p = 0.053). CAV-free survival time was higher in patients with no CMV infectio...
Transplantation Proceedings, 2005
Objective. This retrospective single-center report sought to evaluate the relation of immunosuppressive regimen with the incidence and characteristics of cytomegalovirus (CMV) infection from 1999 to 2003. Patients and methods. Immunosuppression consisted of cyclosporine microemulsion (Neoral), azathioprine (AZA), and prednisolone associated with either thymoglobulin or ATG high-dosage induction from 1999 to 2000 (AZA, 64 patients [AZA-Thymo ϭ 38 patients and AZA-ATG 26 patients]), or cyclosporine microemulsion (Neoral), mycophenolate mofetil (MMF), and prednisolone with low-dose thymoglobulin induction from 2001 onward (n ϭ 52 patients). Ganciclovir preemptive therapy was guided by pp65 antigenemia monitoring without CMV prophylaxis. Results. The study groups were homogeneous with respect to major perioperative risk factors. Comparing the two AZA subgroups no difference emerged as to percentage of pp65 antigenemia-positive, preemptively treated patients reflecting CMV disease incidence and relapses. AZA-Thymo patient showed significantly shorter time to first positive pp65-antigenemia and higher viral load (AZA-Thymo vs AZA-ATG, P ϭ .004 and P ϭ .009). The two subgroups did not differ with regard to incidence of rejection, superinfection, and graft coronary disease. By shifting from AZA to MMF no difference emerged as to incidence and characteristics of CMV infections, but there was a significant reduction in acute rejection and superinfection (AZA vs MMF P ϭ .001 and P ϭ .008). Conclusions. The distinct immunological properties of thymoglobulin versus ATG significantly altered the pattern of CMV expression. MMF with reduced-dose induction did not engender a higher CMV morbidity.
Transplant International, 1996
In this prospective study, cytomegalovirus (CMV) antigenemia was defined as the marker for initiation and episodes of antigenemia as the indicator for the duration of antiviral therapy (CMV hyperimmune globulin and ganciclovir). The CMV antigenemia assay and CMV-specific IgM and IgG antibody tests were used to monitor CMV infection in 22 heart transplant recipients who, between October 1992 and July 1994, were followed up for 6 months 9 A total of 178 out of 627 antigenemia assays tested positive 9 The highest number of positive cells was greater after primary infection than after either reactivation (43.3 vs 0.3; P < 0.01) or reinfection (43.3 vs 9.3; P = NS). Sixty episodes of antigenemia were observed. More episodes of antigenemia were seen after primary infection than after either reactivation (4.6 vs 0.2; P < 0.01) or reinfection (4.6 vs 2.2; P = NS). The detection of antigenemia indicated the initiation of antiviral therapy within 24 h after the blood sample was harvested 9 Therapy was stopped immediately after a subsequent negative result became available 9 Our experience indicates that antigenemia directed antiviral therapy prevents CMV disease after primary and secondary infection in heart transplant recipients.