Antibody-mediated rejection (ABMR) is the leading cause of allograft failure in kidney transplantation. Its histological hallmark is represented by lesions of glomerulitis i.e., inflammatory cells within glomeruli. Current therapies for ABMR fail to prevent chronic allograft damage i.e., transplant glomerulopathy, leading to allograft loss. We used laser microdissection of glomeruli from formalin-fixed allograft biopsies combined with mass spectrometry-based proteomics to describe the proteome modification of 11 active and 10 chronic active ABMR cases compared to 8 stable graft controls. Of 1335 detected proteins, 77 were deregulated in glomerulitis compared to stable grafts, particularly involved in cellular stress mediated by interferons type I and II, leukocyte activation and microcirculation remodeling. Three proteins extracted from this protein profile, TYMP, WARS1 and GBP1, showed a consistent overexpression by immunohistochemistry in glomerular endothelial cells that may represent relevant markers of endothelial stress during active ABMR. In transplant glomerulopathy, 137 proteins were deregulated, which favor a complement-mediated mechanism, wound healing processes through coagulation activation and ultimately a remodeling of the glomerular extracellular matrix, as observed by light microscopy. This study brings novel information on glomerular proteomics of ABMR in kidney transplantation, and highlights potential targets of diagnostic and therapeutic interest.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945687 | PMC |
| http://dx.doi.org/10.3390/biomedicines10030569 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Monoclonal gammopathy is present in one fourth of patients undergoing renal biopsy but is pathogenic only in half of them.
J Nephrol
December 2024
Nephrology, Dialysis and Transplantation Unit, Careggi University Hospital, Largo Brambilla, 3, 50134, Florence, Italy.
Background: About 4-7% of renal biopsies show a monoclonal gammopathy-related nephropathy, such as AL amyloidosis, cast nephropathy, or light chain deposition disease. Both a high prevalence and a causal role of monoclonal gammopathy have been observed in patients with C3 glomerulopathy or thrombotic microangiopathy, although a definitive causative role cannot be established in most cases (potentially monoclonal gammopathy-related nephropathies). A coexisting monoclonal gammopathy has been identified in many cases of nephropathy without a defined causative role (monoclonal gammopathy-unrelated nephropathies).
View Article and Find Full Text PDFDiagnosis, management and treatment of the Alport syndrome - 2024 guideline on behalf of ERKNet, ERA and ESPN.
Nephrol Dial Transplant
December 2024
International Alport Syndrome Alliance and Alport UK, ERKNet ePAG.
Glomerular nephropathy resulting from the genetic defects in COL4A3/4/5 genes including the classical Alport syndrome (AS) is the second commonest hereditary kidney disease characterized by persistent haematuria progressing to the need of kidney replacement therapy, frequently associated with sensorineural deafness, and occasionally with ocular anomalies. Diagnosis and management of COL4A3/4/5 glomerulopathy is a great challenge due to its phenotypic heterogeneity, multiple modes of inheritance, variable expressivity, and disease penetrance of individual variants as well as imperfect prognostic and progression factors and scarce and limited clinical trials, especially in children. As a joint initiative of the European Rare Kidney disease reference Network (ERKNet), European Renal Association (ERA Genes&Kidney) and European Society for Paediatric Nephrology (ESPN) Working Group Hereditary Kidney Disorders, a team of experts including adult and paediatric nephrologists, kidney geneticists, audiologists, ophthalmologists and a kidney pathologist were selected to perform a systematic literature review on 21 clinically relevant PICO (Patient or Population covered, Intervention, Comparator, Outcome) questions.
View Article and Find Full Text PDFRe-Evaluating the Transplant Glomerulopathy Lesion-Beyond Donor-Specific Antibodies.
Transpl Int
December 2024
Nephrology, Medicine, Research in Kidney Transplantation, Faculty in Human Translational Immunology and Translational Biomedicine, Yale School of Medicine, New Haven, CT, United States.
There have been significant advances in short-term outcomes in renal transplantation. However, longer-term graft survival has improved only minimally. After the first post-transplant year, it has been estimated that chronic allograft damage is responsible for 5% of graft loss per year.
View Article and Find Full Text PDFObesity-Related Kidney Disease in Bariatric Surgery Candidates.
Obes Surg
December 2024
Department of Nephrology, Unidade Local de Saúde de Santo António, (ULS Santo António), Porto, Portugal.
Article Synopsis
- Obesity adversely affects kidney health, but the specific kidney dysfunction markers in bariatric surgery candidates are not well understood, prompting a study comparing these biomarkers to those of living kidney donors.
- The study involved matching 200 bariatric candidates with 200 living kidney donors based on sex and age, using a 24-hour urine collection to assess protein levels and kidney function.
- Findings indicated that patients with obesity had higher creatinine clearance and proteinuria than kidney donors, underscoring the need to reconsider how kidney function is evaluated in obese individuals considering bariatric surgery, particularly regarding body surface area adjustments.
Late Recurrence of C3 Glomerulopathy After SARS-CoV-2 Infection in a Long-Term Kidney Transplant Recipient: A Case Report.
Am J Case Rep
December 2024
Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Roma, Italy.
Article Synopsis
- Kidney transplantation is the best treatment for end-stage kidney disease, but long-term success can be affected by issues like recurrence of native kidney diseases such as C3 glomerulopathy (C3GN).
- A case study documented a female kidney transplant recipient whose kidney function declined after 28 years due to two SARS-CoV-2 infections, alongside evidence of chronic rejection and features of C3GN in her recent biopsy.
- The findings suggest that C3GN may have recurred late in this patient as a result of complement activation triggered by the SARS-CoV-2 infections, indicating a potential new risk factor for post-transplant complications.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!