Imperial College London

DrCandiceRoufosse

Faculty of MedicineDepartment of Immunology and Inflammation

Clinical Reader in Renal Pathology
 
 
 
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Contact

 

+44 (0)20 3313 3280c.roufosse

 
 
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Location

 

Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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192 results found

Roufosse C, Cook H, Dominy K, Willicombe M, Beadle J, Szydlo R, McLean A, Toulza Fet al., 2022, Diagnostic application of transcripts associated with antibody-mediated rejection in kidney transplant biopsies, Nephrology Dialysis Transplantation, Vol: 37, Pages: 1576-1584, ISSN: 0931-0509

BackgroundThe diagnosis of antibody-mediated rejection (AMR) is reached using the Banff Classification for Allograft Pathology, which now includes gene expression analysis. In this study, we investigate the application of “Increased Expression Of Thoroughly Validated Gene Transcripts/Classifiers Strongly Associated With AMR” as a diagnostic criteria.MethodWe used qRT-PCR for 10 genes associated with AMR in a retrospective cohort of 297 transplant biopsies, including biopsies that met the full diagnostic criteria for AMR, even without molecular data (AMR, n = 27); biopsies that showed features of AMR, but that would only meet criteria for AMR with increased transcripts (AMRsusp, n = 49) and biopsies that would never meet criteria for AMR (No-AMR, n = 221).ResultsA 10-gene AMR score trained by a receiver-operating characteristic to identify AMR found 16 cases with a high score amongst the AMRsusp cases (AMRsusp-high) that had significantly worse graft survival than those with a low score (AMRsusp-low) (n = 33). In both univariate and multivariate Cox regression analysis, the AMR 10-gene score was significantly associated with an increased hazard ratio for graft loss in the AMRsusp group (HR 1.109, p = 0.004 and HR 1.138, p = 0.012), but not in the whole cohort. Net reclassification index and integrated discrimination improvement analyses demonstrated improved risk classification and superior discrimination respectively for graft loss when considering the gene score in addition to histological and serological data, but only in the AMRsusp group, not the whole cohort.ConclusionsThis study provides evidence that a gene score strongly associated with AMR helps identify cases at higher risk of graft loss in biopsies that are suspicious for AMR but don’t meet full criteria.

Journal article

Becker JU, Seron D, Rabant M, Roufosse C, Naesens Met al., 2022, Evolution of the Definition of Rejection in Kidney Transplantation and Its Use as an Endpoint in Clinical Trials, TRANSPLANT INTERNATIONAL, Vol: 35, ISSN: 0934-0874

Journal article

Seron D, Rabant M, Becker JU, Roufosse C, Bellini MI, Boehmig GA, Budde K, Diekmann F, Glotz D, Hilbrands L, Loupy A, Oberbauer R, Pengel L, Schneeberger S, Naesens Met al., 2022, Proposed Definitions of T Cell-Mediated Rejection and Tubulointerstitial Inflammation as Clinical Trial Endpoints in Kidney Transplantation, TRANSPLANT INTERNATIONAL, Vol: 35, ISSN: 0934-0874

Journal article

Roufosse C, Becker JU, Rabant M, Seron D, Bellini MI, Boehmig GA, Budde K, Diekmann F, Glotz D, Hilbrands L, Loupy A, Oberbauer R, Pengel L, Schneeberger S, Naesens Met al., 2022, Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation, TRANSPLANT INTERNATIONAL, Vol: 35, ISSN: 0934-0874

Journal article

Gray-Rodriguez S, Jensen M, Otero-Jimenez M, Hanley B, Swann O, Ward P, Salguero F, Querido N, Farkas I, Velentza-Almpani E, Weir J, Barclay W, Carroll M, Jaunmuktane Z, Brandner S, Pohl U, Allinson K, Thom M, Troakes C, Al-Sarraj S, Sastre M, Gveric D, Gentleman S, Roufosse C, Osborn M, Alegre-Abarrategui Jet al., 2022, Detection of SARS-CoV-2 within enteric neurons and in brain, Publisher: WILEY, ISSN: 0305-1846

Conference paper

Tempest-Roe S, Prendecki M, McAdoo S, Tanna A, Turner-Stokes T, Masuda E, Willicombe M, Cook T, Roufosse C, Taube D, Pusey C, Tam Fet al., 2022, Inhibition of spleen tyrosine kinase decreases donor specific antibody levels in a rat model of sensitization, Scientific Reports, Vol: 12, ISSN: 2045-2322

Antibody mediated rejection is a major cause of renal allograft loss. Circulating preformed donor specific antibodies (DSA) can result as a consequence of blood transfusion, pregnancy or prior transplantation. Current treatment strategies are limited due to partial or transient efficacy, adverse side-effects or patient unsuitability. Previous in vivo studies exploring autoimmune diseases have shown that spleen tyrosine kinase (SYK) signalling is involved in the development of pathogenic autoantibody. The role of SYK in allogenic antibody production is unknown, and we investigated this in a rodent model of sensitization, established by the transfusion of F344 whole blood into LEW rats. Two-week treatment of sensitized rats with selective SYK inhibitor fostamatinib strongly blocked circulating DSA production without affecting overall total immunoglobulin levels, and inhibition was sustained up to 5 weeks post-completion of the treatment regimen. Fostamatinib treatment did not affect mature B cell subset or plasma cell levels, which remained similar between non-treated controls, vehicle treated and fostamatinib treated animals. Our data indicate fostamatinib may provide an alternative therapeutic option for patients who are at risk of sensitization following blood transfusion while awaiting renal transplant.

Journal article

Gray-Rodriguez S, Jensen MP, Otero-Jimenez M, Hanley B, Swann OC, Ward PA, Salguero FJ, Querido N, Farkas I, Velentza-Almpani E, Weir J, Barclay WS, Carroll MW, Jaunmuktane Z, Brandner S, Pohl U, Allinson K, Thom M, Troakes C, Al-Sarraj S, Sastre M, Gveric D, Gentleman S, Roufosse C, Osborn M, Alegre-Abarrategui Jet al., 2022, Multisystem screening reveals SARS-CoV-2 in neurons of the myenteric plexus and in megakaryocytes, Journal of Pathology, Vol: 257, ISSN: 0022-3417

SARS-CoV-2, the causative agent of COVID-19, typically manifests as a respiratory illness although extrapulmonary involvement, such as in the gastrointestinal tract and nervous system, as well as frequent thrombotic events, are increasingly recognised. How this maps onto SARS-CoV-2 organ tropism at the histological level, however, remains unclear. Here, we perform a comprehensive validation of a monoclonal antibody against the SARS-CoV-2 nucleocapsid protein (NP) followed by systematic multisystem organ immunohistochemistry analysis of the viral cellular tropism in tissue from 36 patients, 16 post-mortem cases and 16 biopsies with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 status from the peaks of the pandemic in 2020 and four pre-COVID post-mortem controls. SARS-CoV-2 anti-NP staining in the post-mortem cases revealed broad multiorgan involvement of the respiratory, digestive, haematopoietic, genitourinary and nervous systems, with a typical pattern of staining characterised by punctate paranuclear and apical cytoplasmic labelling. The average time from symptom onset to time of death was shorter in positively versus negatively stained post-mortem cases (mean = 10.3 days versus mean = 20.3 days, p = 0.0416, with no cases showing definitive staining if the interval exceeded 15 days). One striking finding was the widespread presence of SARS-CoV-2 NP in neurons of the myenteric plexus, a site of high ACE-2 expression, the entry receptor for SARS-CoV-2, and one of the earliest affected cells in Parkinson's disease. In the bone marrow, we observed viral SARS-CoV-2 NP within megakaryocytes, key cells in platelet production and thrombus formation. In 15 tracheal biopsies performed in patients requiring ventilation, there was a near complete concordance between immunohistochemistry and PCR swab results. Going forward, our findings have relevance to correlating clinical symptoms to the organ tropism of

Journal article

Arturs C, Roufosse C, 2021, Forging the tools for a computer-aided workflow in transplant pathology, LANCET DIGITAL HEALTH, Vol: 4, Pages: E2-E3

Journal article

Aguiar PV, Ramirez-Bajo MJ, Sanchez Salom L, Roufosse C, Cuatrecasas M, Rovira J, Bañón-Maneus E, Fondevila C, Campistol JM, Uva P, Drachenberg C, Diekmann Fet al., 2021, P.156: Transcriptomic Profile in Pancreas Biopsies for Monitoring Graft Rejection., Transplantation, Vol: 105

Journal article

Prendecki M, Gulati K, Turner-Stokes T, Bhangal G, Chiappo D, Woollard K, Cook HT, Tam FW, Roufosse C, Pusey CD, McAdoo SPet al., 2021, Characterisation of an enhanced preclinical model of experimental MPO-ANCA autoimmune vasculitis, Journal of Pathology, Vol: 255, Pages: 107-119, ISSN: 0022-3417

Experimental autoimmune vasculitis (EAV) is a model of antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) induced by immunisation of susceptible rat strains with myeloperoxidase (MPO). Animals develop circulating MPO-ANCA, pulmonary haemorrhage and glomerulonephritis, although renal injury is mild and recovers spontaneously without treatment. In this study we aimed to augment the severity of glomerulonephritis. Following induction of EAV on day 0, a sub-nephritogenic dose of nephrotoxic serum (NTS) containing heterologous antibodies to glomerular basement membrane was administered on day 14. This resulted in a significant increase in disease severity at day 28 compared to MPO immunisation alone - with more urinary abnormalities, infiltrating glomerular leucocytes, and crescent formation that progressed to glomerular and tubulointerstitial scarring by day 56, recapitulating important features of human disease. Importantly, the glomerulonephritis remained pauci-immune, and was strictly dependent on the presence of autoimmunity to MPO, as there was no evidence of renal disease following administration of sub-nephritogenic NTS alone or after immunisation with a control protein in place of MPO. Detailed phenotyping of glomerular leucocytes identified an early infiltrate of non-classical monocytes following NTS administration that, in the presence of autoimmunity to MPO, may initiate the subsequent influx of classical monocytes which augment glomerular injury. We also showed that this model can be used to test novel therapeutics by using a small molecule kinase inhibitor (fostamatinib) that rapidly attenuated both glomerular and pulmonary injury over a four-day treatment period. We believe that this enhanced model of MPO-AAV will prove useful for the study of glomerular leucocyte behaviour and novel therapeutics in AAV in the future. This article is protected by copyright. All rights reserved.

Journal article

Kapp ME, Fogo AB, Roufouse C, Najafian B, Radhakrishnan J, Mohan S, Miller SE, D'Agati VD, Silberzweig J, Barbar T, Gopalan T, Srivatana V, Mokrzycki MH, Benstein JA, Ng Y-H, Lentine KL, Aggarwal V, Perl J, Salenger P, Koyner JL, Josephson MA, Heung M, Velez JC, Ikizler A, Vijayan A, William P, Thajudeen B, Slepian MJet al., 2021, Renal Considerations in COVID-19: Biology, Pathology, and Pathophysiology., ASAIO J, Vol: 67, Pages: 1087-1096

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged into a worldwide pandemic of epic proportion. Beyond pulmonary involvement in coronavirus disease 2019 (COVID-19), a significant subset of patients experiences acute kidney injury. Patients who die from severe disease most notably show diffuse acute tubular injury on postmortem examination with a possible contribution of focal macro- and microvascular thrombi. Renal biopsies in patients with proteinuria and hematuria have demonstrated a glomerular dominant pattern of injury, most notably a collapsing glomerulopathy reminiscent of findings seen in human immunodeficiency virus (HIV) in individuals with apolipoprotein L-1 (APOL1) risk allele variants. Although various mechanisms have been proposed for the pathogenesis of acute kidney injury in SARS-CoV-2 infection, direct renal cell infection has not been definitively demonstrated and our understanding of the spectrum of renal involvement remains incomplete. Herein we discuss the biology, pathology, and pathogenesis of SARS-CoV-2 infection and associated renal involvement. We discuss the molecular biology, risk factors, and pathophysiology of renal injury associated with SARS-CoV-2 infection. We highlight the characteristics of specific renal pathologies based on native kidney biopsy and autopsy. Additionally, a brief discussion on ancillary studies and challenges in the diagnosis of SARS-CoV-2 is presented.

Journal article

Roufosse C, 2021, Super-Resolved Imaging for Translational Research and Diagnosis in Renal Pathology, 13th Joint Meeting of the British-Division-of-The-International-Academy-of-Pathology and The-Pathological-Society-of-Great-Britain-and-Ireland (Manchester Pathology), Publisher: WILEY, Pages: S11-S11, ISSN: 0022-3417

Conference paper

Adam BA, Murakami N, Reid G, Du K, Jasim R, Boils CL, Bu L, Hill PD, Murray AG, Renaudin K, Roufosse C, Weins A, Wen K, Riella LV, Mengel Met al., 2021, Gene Expression Profiling in Kidney Transplants with Immune Checkpoint Inhibitor?Associated Adverse Events, CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol: 16, Pages: 1376-1386, ISSN: 1555-9041

Journal article

Kousios A, Mcadoo S, Blakey S, Moran L, Atta M, Tam FW, Cook HT, Chaidos A, Roufosse Cet al., 2021, Masked crystalline light chain tubulopathy and podocytopathy with focal segmental glomerulosclerosis: a rare MGRS-associated renal lesion, Histopathology, Vol: 79, Pages: 265-268, ISSN: 1365-2559

Monoclonal Gammopathy of Renal Significance (MGRS) encompasses a wide spectrum of histopathology. Characterizing rare forms of MGRS-related renal pathology remains work in progress. Light chain crystalline podocytopathy in the context of MGRS, either in isolation or combined with proximal tubulopathy (LCPT) has rarely been described. Unravelling MGRS pathologies is critical for patient management and often requires ancillary techniques for antigen retrieval to demonstrate light chain (LC) restriction on immunofluorescence (IF).

Journal article

Barba T, Oberbarnscheidt MH, Rabeyrin M, Roufosse C, Moran L, Koenig A, Mathias V, Saison C, Dubois V, Morelon E, Xu-Dubois Y-C, Lakkis F, Thaunat Oet al., 2021, THE BIATHLETE'S DILEMMA: UNRAVELLING THE MOLECULAR MECHANISMS OF THE IMMUNE PRIVILEGE OF GRAFT ENDOTHELIUM DURING TCMR, Publisher: WILEY, Pages: 9-9, ISSN: 0934-0874

Conference paper

Gulati K, Roufosse C, McAdoo SP, 2021, Diffuse crescentic glomerulonephritis presenting with preserved renal function, RHEUMATOLOGY, Vol: 60, Pages: 18-20, ISSN: 1462-0324

Journal article

Garcia E, Lightley J, Kumar S, Kalita R, Gorlitz F, Alexandrov Y, Cook T, Dunsby C, Neil MAA, Roufosse CA, French PMWet al., 2021, Application of direct stochastic optical reconstruction microscopy (dSTORM) to the histological analysis of human glomerular disease, JOURNAL OF PATHOLOGY CLINICAL RESEARCH, Vol: 7, Pages: 438-445

Journal article

Cicalese PA, Rizvi SA, Roufosse C, Batal I, Hellmich M, Ernst A, Moos K, Clahsen-van Groningen M, Weidemann A, Mohan C, Nguyen HV, Becker JUet al., 2021, DEEP LEARNING DIAGNOSIS OF ANTIBODY-MEDIATED REJECTION (AMR) ON GLOMERULAR TRANSECTIONS, 58th Congress of the European-Renal-Association (ERA)-European-Dialysis-and-Transplant-Association (EDTA), Publisher: OXFORD UNIV PRESS, ISSN: 0931-0509

Conference paper

Nikolopoulou A, Teixeira C, Cook H, Roufosse C, Cairns THD, Levy JB, Pusey C, Griffith MEet al., 2021, Membranous nephropathy associated with viral infection, Clinical Kidney Journal, Vol: 14, Pages: 876-883, ISSN: 2048-8505

BackgroundMembranous nephropathy (MN) can be associated with hepatitis infection and less commonly with human immunodeficiency virus (HIV) infection. The significance of anti-phospholipase A2 receptor (PLA2R) and anti-thrombospondin type 1 domain-containing 7A (THSD7A) antibodies in this setting is unclear.MethodsWe describe the clinical, histopathological and outcome data of 19 patients with MN and hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV infection identified through our renal biopsy database and the association with anti-PLA2R antibodies and anti-THSD7A antibodies.ResultsThe cohort consisted of 19 patients, 8 male and 11 female, with a median age of 42 years (range 23–74). HBV infection was found in six cases, HCV in four and HIV in nine (two HIV patients had HBV co-infection and one HCV co-infection). PLA2R staining on biopsy was positive in 10/19 patients: 4 with HBV-MN, 3 with HCV-MN and 3 with HIV-MN and circulating anti-PLA2R antibodies were detected in 7/10 cases. THSD7A staining on biopsy was positive in three PLA2R-negative cases, one with HBV-MN and two with HIV-MN. Mean proteinuria was higher in the PLA2R-positive group and the median urinary protein:creatinine ratio (uPCR) was 963 mg/mmol (range 22–2406) compared with the PLA2R-negative group [median uPCR 548 mg/mmol (range 65–1898); P = 0.18 Mann–Whitney]. Spontaneous remission occurred in 6/19 patients and after-treatment remission occurred in 7/11 patients. Renal function was preserved in all but two patients who required haemodialysis 2 and 11 years from diagnosis.ConclusionsWe describe a cohort of patients with MN associated with viral infection, including rare cases of HIV-MN with PLA2R and THSD7A positivity. The mechanism of coincidental or viral-related MN needs to be investigated further.

Journal article

Cicalese PA, Rizvi SA, Wang V, Patibandla S, Yuan P, Zare S, Moos K, Batal I, Clahsen-van Groningen M, Roufosse C, Becker J, Mohan C, Hien VNet al., 2021, MorphSet: Improving Renal Histopathology Case Assessment Through Learned Prognostic Vectors, International Conference on Medical Image Computing and Computer Assisted Intervention (MICCAI), Publisher: SPRINGER INTERNATIONAL PUBLISHING AG, Pages: 319-328, ISSN: 0302-9743

Conference paper

Naesens M, Haas M, Loupy A, Roufosse C, Mengel Met al., 2020, Does the definition of chronic active T cell-mediated rejection need revisiting?, AMERICAN JOURNAL OF TRANSPLANTATION, Vol: 21, Pages: 1689-1690, ISSN: 1600-6135

Journal article

Dattani R, Corbett RW, Galliford J, Hill P, Cairns T, Cook HT, Roufosse C, Ashby DRet al., 2020, The Effect of Kidney Biopsy on Glomerular Filtration Rate: A Frequent Patient Concern, AMERICAN JOURNAL OF NEPHROLOGY, Vol: 51, Pages: 903-906, ISSN: 0250-8095

Journal article

Roufosse C, Drachenberg C, Renaudin K, Willicombe M, Toulza F, Dominy K, McLean A, Simmonds N, de Kort H, Cantarovitch D, Scalea J, Mengel M, Adam Bet al., 2020, Molecular assessment of antibody-mediated rejection in human pancreas allograft biopsies, Clinical Transplantation, Vol: 34, Pages: 1-13, ISSN: 0902-0063

Pancreas transplant longevity is limited by immune rejection, which is diagnosed by graft biopsy using the Banff Classification. The histological criteria for antibody-mediated rejection (AMR) are poorly reproducible and inconsistently associated with outcome. We hypothesized that a 34-gene set associated with antibody-mediated rejection in other solid organ transplants could improve diagnosis in pancreas grafts. The AMR 34-gene set, comprising endothelial, natural killer cell and inflammatory genes, was quantified using the NanoString platform in 52 formalin-fixed, paraffin-embedded pancreas transplant biopsies from 41 patients: 15 with pure AMR or mixed rejection, 22 with T cell-mediated rejection/borderline and 15 without rejection. The AMR 34-gene set was significantly increased in pure AMR and mixed rejection (P = .001) vs no rejection. The gene set predicted histological AMR with an area under the receiver operating characteristic curve (ROC AUC) of 0.714 (P = .004). The AMR 34-gene set was the only biopsy feature significantly predictive of allograft failure in univariate analysis (P = .048). Adding gene expression to DSA and histology increased ROC AUC for the prediction of failure from 0.736 to 0.770, but this difference did not meet statistical significance. In conclusion, assessment of transcripts has the potential to improve diagnosis and outcome prediction in pancreas graft biopsies.

Journal article

Tennekoon HD, Kousios A, Gardiner R, Moran L, Goodall D, Galliford J, Taube D, Roufosse Cet al., 2020, Anticoagulant-related nephropathy in a renal transplant recipient., Kidney International Reports, Vol: 5, Pages: 2089-2096, ISSN: 2468-0249

Journal article

Neil D, Moran L, Horsfield C, Curtis E, Swann O, Barclay W, Hanley B, Hollinshead M, Roufosse Cet al., 2020, Ultrastructure of cell trafficking pathways and coronavirus: how to recognise the wolf amongst the sheep, JOURNAL OF PATHOLOGY, Vol: 252, Pages: 346-357, ISSN: 0022-3417

Journal article

Toulza F, Dominy K, Cook H, Galliford J, Beadle J, McLean A, Roufosse Cet al., 2020, Technical considerations when designing a gene expression panel for renal transplant diagnosis, Scientific Reports, Vol: 10, ISSN: 2045-2322

Gene expression analysis is emerging as a new diagnostic tool in transplant pathology, in particular for the diagnosis of antibody-mediated rejection. Diagnostic gene expression panels are defined on the basis of their pathophysiological relevance, but also need to be tested for their robustness across different preservatives and analysis platforms. The aim of this study is the investigate the effect of tissue sampling and preservation on candidate genes included in a renal transplant diagnostic panel. Using the NanoString platform, we compared the expression of 219 genes in 51 samples, split for formalin-fixation and paraffin-embedding (FFPE) and RNAlater preservation (RNAlater). We found that overall, gene expression significantly correlated between FFPE and RNAlater samples. However, at the individual gene level, 46 of the 219 genes did not correlate across the 51 matched FFPE and RNAlater samples. Comparing gene expression results using NanoString and qRT-PCR for 18 genes in the same pool of RNA (RNAlater), we found a significant correlation in 17/18 genes. Our study indicates that, in samples from the same routine diagnostic renal transplant biopsy procedure split for FFPE and RNAlater, 21% of 219 genes of potential biological significance do not correlate in expression. Whether this is due to fixatives or tissue sampling, selection of gene panels for routine diagnosis should take this information into consideration.

Journal article

Hanley B, Naresh KN, Roufosse C, Nicholson AG, Weir J, Cooke GS, Thursz M, Manousou P, Corbett R, Goldin R, Al-Sarraj S, Abdolrasouli A, Swann OC, Baillon L, Penn R, Barclay WS, Viola P, Osborn Met al., 2020, Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study, The Lancet Microbe, Vol: 1, Pages: e245-e253, ISSN: 2666-5247

BackgroundSevere COVID-19 has a high mortality rate. Comprehensive pathological descriptions of COVID-19 are scarce and limited in scope. We aimed to describe the histopathological findings and viral tropism in patients who died of severe COVID-19.MethodsIn this case series, patients were considered eligible if they were older than 18 years, with premortem diagnosis of severe acute respiratory syndrome coronavirus 2 infection and COVID-19 listed clinically as the direct cause of death. Between March 1 and April 30, 2020, full post-mortem examinations were done on nine patients with confirmed COVID-19, including sampling of all major organs. A limited autopsy was done on one additional patient. Histochemical and immunohistochemical analyses were done, and histopathological findings were reported by subspecialist pathologists. Viral quantitative RT-PCR analysis was done on tissue samples from a subset of patients.FindingsThe median age at death of our cohort of ten patients was 73 years (IQR 52–79). Thrombotic features were observed in at least one major organ in all full autopsies, predominantly in the lung (eight [89%] of nine patients), heart (five [56%]), and kidney (four [44%]). Diffuse alveolar damage was the most consistent lung finding (all ten patients); however, organisation was noted in patients with a longer clinical course. We documented lymphocyte depletion (particularly CD8-positive T cells) in haematological organs and haemophagocytosis. Evidence of acute tubular injury was noted in all nine patients examined. Major unexpected findings were acute pancreatitis (two [22%] of nine patients), adrenal micro-infarction (three [33%]), pericarditis (two [22%]), disseminated mucormycosis (one [10%] of ten patients), aortic dissection (one [11%] of nine patients), and marantic endocarditis (one [11%]). Viral genomes were detected outside of the respiratory tract in four of five patients. The presence of subgenomic viral RNA transcripts provided evidence of

Journal article

Mengel M, Loupy A, Haas M, Roufosse C, Naesens M, Akalin E, Clahsen-van Groningen MC, J Dagobert, Demetris AJ, Duong van Huyen JP, Gueguen J, Issa F, Robin B, Rosales I, Von der Thüsen JH, Sanchez-Fueyo A, Smith RN, Wood K, Adam B, Colvin RBet al., 2020, Banff 2019 Meeting Report: Molecular diagnostics in solid organ transplantation - Consensus for the Banff Human Organ Transplant (B-HOT) gene panel and open source multicenter validation, American Journal of Transplantation, Vol: 20, ISSN: 1600-6135

This Meeting Report from the XVth Banff conference describes the creation of a multi-organ transplant gene panel by the Banff Molecular Diagnostics Working Group (MDWG). This Banff Human Organ Transplant (B-HOT) panel is the culmination of previous work by the MDWG to identify a broadly useful gene panel based on whole transcriptome technology. A data driven process distilled a gene list from peer reviewed comprehensive microarray studies that discovered and validated their use in kidney, liver, heart and lung transplant biopsies. These were supplemented by genes that define relevant cellular pathways and cell types plus 12 reference genes used for normalization. The 770 gene B-HOT panel includes the most pertinent genes related to rejection, tolerance, viral infections, and innate and adaptive immune responses. This commercially available panel uses the NanoString platform, which can quantitate transcripts from formalin fixed paraffin embedded samples. The B-HOT panel will facilitate multicenter collaborative clinical research using archival samples and permit the development of an open source large database of standardized analyzes, thereby expediting clinical validation studies. The MDWG believes that a pathogenesis and pathway based molecular approach will be valuable for investigators and promote therapeutic decision-making and clinical trials.

Journal article

Turner-Stokes T, Garcia Diaz A, Pinheiro D, Prendecki M, McAdoo SP, Roufosse C, Cook HT, Pusey CD, Woollard KJet al., 2020, Live imaging of monocyte subsets in immune complex-mediated glomerulonephritis reveals distinct phenotypes and effector functions., Journal of the American Society of Nephrology, Vol: 31, Pages: 1-1, ISSN: 1046-6673

BACKGROUND: Immune complexes within glomerular capillary walls cause crescentic GN (CrGN). Monocytes and macrophages are important in mediating CrGN, but little work has been done to phenotype the subpopulations involved and determine their respective contributions to glomerular inflammation. METHODS: Live glomerular imaging using confocal microscopy monitored intravascular monocyte subset behavior during nephrotoxic nephritis (NTN) in a novel WKY-hCD68-GFP monocyte/macrophage reporter rat strain. Flow cytometry and qPCR further analyzed ex vivo the glomerular leukocyte infiltrate during NTN. RESULTS: Non-classical monocytes surveyed the glomerular endothelium via lymphocyte function-associated antigen 1 (LFA-1) in the steady state. During NTN, non-classical monocytes were recruited first, but subsequent recruitment and retention of classical monocytes was associated with glomerular damage. Monocytes recruited to the glomerular vasculature did not undergo transendothelial migration. This finding suggests that inflammation in immune complex-mediated CrGN is predominantly intravascular, driven by dynamic interactions between intravascular blood monocytes and the endothelium. Glomerular endothelium and non-classical monocytes overexpressed a distinct chemokine axis, which may orchestrate inflammatory myeloid cell recruitment and expression of damage mediators. Reduced classical monocyte recruitment in Lewis rats during NTN confirmed a role for CD16 in mediating glomerular damage. CONCLUSIONS: Monocyte subsets with distinct phenotypes and effector functions may be important in driving inflammation in experimental CrGN resulting from immune complexes formed within the glomerular capillary wall. LFA-1-dependent endothelial surveillance by non-classical monocytes may detect immune complexes through CD16, orchestrating the inflammatory response through intravascular retention of classical monocytes, which results in glomerular damage and proteinuria.

Journal article

Loupy A, Haas M, Roufosse C, Naesens M, Adam B, Afrouzian M, Akalin E, Alachkar N, Bagnasco S, Becker JU, Cornell LD, Clahsen-van Groningen MC, Demetris AJ, Dragun D, Duong van Huyen J-P, Farris AB, Fogo AB, Gibson IW, Glotz D, Gueguen J, Kikic Z, Kozakowski N, Kraus E, Lefaucheur C, Liapis H, Mannon RB, Montgomery RA, Nankivell BJ, Nickeleit V, Nickerson P, Rabant M, Racusen L, Randhawa P, Robin B, Rosales IA, Sapir-Pichhadze R, Schinstock CA, Seron D, Singh HK, Smith RN, Stegall MD, Zeevi A, Solez K, Colvin RB, Mengel Met al., 2020, The banff 2019 kidney meeting report (I): updates on and clarification of criteria for T cell- and antibody-mediated rejection., American Journal of Transplantation, Vol: 20, Pages: 2318-2331, ISSN: 1600-6135

The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of the American Society for Histocompatibility and Immunogenetics in Pittsburgh, PA (USA) and focused on refining recent updates to the classification, advances from the Banff working groups, and standardization of molecular diagnostics. This report on kidney transplant pathology details clarifications and refinements to the criteria for chronic active (CA) T cell-mediated rejection (TCMR), borderline, and antibody-mediated rejection (ABMR). The main focus of kidney sessions was on how to address biopsies meeting criteria for CA TCMR plus borderline or acute TCMR. Recent studies on the clinical impact of borderline infiltrates were also presented to clarify whether the threshold for interstitial inflammation in diagnosis of borderline should be i0 or i1. Sessions on ABMR focused on biopsies showing microvascular inflammation in the absence of C4d staining or detectable donor-specific antibodies; the potential value of molecular diagnostics in such cases and recommendations for use of the latter in the setting of solid organ transplantation are presented in the accompanying meeting report. Finally, several speakers discussed the capabilities of artificial intelligence and the potential for use of machine learning algorithms in diagnosis and personalized therapeutics in solid organ transplantation.

Journal article

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