Background: Cytomegalovirus (CMV) is a suggested risk factor for the development of chronic allograft nephropathy. Transforming growth factor-beta (TGF-beta) and platelet-derived growth factor (PDGF) are important molecules in this process. We analysed the impact of persistent CMV infection in kidney allografts on the expression of growth factors, adhesion molecules and inflammation markers.
Methods: In a population of 172 renal transplant recipients, CMV was diagnosed in 82 patients by pp65 antigenaemia test and viral cultures. Biopsies taken after CMV infection were available from 48 of the 82 patients for the demonstration of CMV antigens by immunohistochemistry and in situ DNA hybridization. Biopsy material for further analyses was available from 16 CMV patients. Five patients with no previous CMV infection were used as controls. Biopsy histology was scored according to Banff 97 classification.
Results: In 11 out of 16 patients, persistent CMV antigens and/or DNA were demonstrated in the biopsy >2 months after the last positive finding in blood or urine. Increased expression of TGF-beta1 was recorded in tubuli and in arterial endothelium in biopsies with a positive CMV finding compared with controls. Also, the expression of PDGF-AA was increased in tubuli and somewhat in arterial endothelium in CMV-positive biopsies. The expression of intercellular adhesion molecule-1 (ICAM-1) was increased significantly in peritubular capillary endothelium. Vascular intimal thickening was increased in the biopsies with persistent CMV infection.
Conclusions: Persistent CMV infection in kidney allografts was associated with increased vascular changes and increased expression of TGF-beta1, PDGF-AA and ICAM-1.
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http://dx.doi.org/10.1093/ndt/gfh714 | DOI Listing |
Vaccines (Basel)
January 2025
The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7DQ, UK.
After four decades of intensive research, traditional vaccination strategies for HIV-1 remain ineffective due to HIV-1's extraordinary genetic diversity and complex immune evasion mechanisms. Cytomegaloviruses (CMV) have emerged as a novel type of vaccine vector with unique advantages due to CMV persistence and immunogenicity. Rhesus macaques vaccinated with molecular clone 68-1 of RhCMV (RhCMV68-1) engineered to express simian immunodeficiency virus (SIV) immunogens elicited an unconventional major histocompatibility complex class Ib allele E (MHC-E)-restricted CD8 T-cell response, which consistently protected over half of the animals against a highly pathogenic SIV challenge.
View Article and Find Full Text PDFSurg Pract Sci
March 2024
Department of Surgery, Division of Multiorgan Transplant and Hepatobiliary Surgery, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX, 77555-0655, USA.
Introduction: In renal transplantation, donor hepatitis C virus (HCV) status is crucial to consider when selecting a recipient given the high likelihood of transmission. We analyzed the effect of donor HCV status on post-renal transplant rejection and virologic infectious outcomes using electronic health record data from multiple US health care organizations.
Methods: Using real world data from electronic health records of renal transplant recipients, a propensity score-matched case-control study of one-year renal transplant outcomes was conducted on cohorts of HCV-negative recipients who received an organ from an HCV-positive donor (HCV D+/R-) versus from an HCV-negative donor (HCV D-/R-).
BMJ Case Rep
January 2025
Pediatrics, Rutgers New Jersey Medical School, Newark, New Jersey, USA.
This case report presents a late preterm infant diagnosed with severe cerebellar hypoplasia and microcephaly secondary to congenital cytomegalovirus (cCMV) infection. Initially suspected to have Dandy-Walker malformation, postnatal MRI revealed significant cerebellar hypoplasia, without other typical cCMV findings. The diagnosis was confirmed by the presence of CMV in serum and urine.
View Article and Find Full Text PDFBiomedica
December 2024
Departamento de Microbiología, Facultad de Salud, Universidad del Valle, Cali, Colombia; Genetic Immunotherapy Section, Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
A 45-year-old male patient presented with a persistent cough lasting four months, accompanied by fever and significant weight loss. A chest computed tomography revealed cryptogenic pneumonia, and subsequent investigations identified a positive cytomegalovirus (CMV) viral load in bronchoalveolar lavage. A transbronchial biopsy confirmed intranuclear basophilic inclusions indicative of CMV infection.
View Article and Find Full Text PDFAm J Transplant
January 2025
Division of Endocrinology, Diabetes, Metabolism & Nutrition, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Treating acute rejection of a pancreas transplant in a severely immunocompromised patient with viral opportunistic infection is challenging due to the balance of rescuing from rejection without worsening the morbidity of infection and prolonging the infection episode. We present a case involving a pancreas-after-kidney transplant in a patient with CMV high-risk discordance (donor positive/recipient negative) and chronic lymphopenia who developed difficult-to-treat CMV disease approximately six months after pancreas transplant. Following the withdrawal of the antimetabolite due to the persistent CMV DNAemia and lymphopenia, the patient experienced acute pancreas rejection without adequate and sustained response to treatment with steroids and Thymoglobulin.
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