Imperial College London

Emeritus ProfessorCharlesPusey

Faculty of MedicineDepartment of Immunology and Inflammation

Emeritus Professor of Medicine
 
 
 
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Contact

 

+44 (0)20 3313 2308c.pusey

 
 
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Assistant

 

Miss Anjli Jagpal +44 (0)20 3313 3152

 
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Location

 

5N2Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

578 results found

Prendecki M, McAdoo SP, Turner-Stokes T, Garcia-Diaz A, Orriss I, Woollard KJ, Behmoaras J, Cook HT, Unwin R, Pusey CD, Aitman TJ, Tam FWKet al., 2022, Glomerulonephritis and autoimmune vasculitis are independent of P2RX7 but may depend on alternative inflammasome pathways., Journal of Pathology, Vol: 257, ISSN: 0022-3417

P2RX7, an ionotropic receptor for extracellular ATP, is expressed on immune cells, including macrophages, monocytes and dendritic cells and is up-regulated on non-immune cells following injury. P2RX7 plays a role in many biological processes, including production of pro-inflammatory cytokines such as IL-1β via the canonical inflammasome pathway. P2RX7 has been shown to be important in inflammation and fibrosis and may also play a role in autoimmunity. We have developed and phenotyped a novel P2RX7 knock-out (KO) inbred rat strain and taking advantage of the human-resembling unique histopathological features of rat models of glomerulonephritis, we induced three models of disease: nephrotoxic nephritis, experimental autoimmune glomerulonephritis, and experimental autoimmune vasculitis. We found that deletion of P2RX7 does not protect rats from models of experimental glomerulonephritis or the development of autoimmunity. Notably, treatment with A-438079, a P2RX7 antagonist, was equally protective in WKY WT and P2RX7 KO rats, revealing its 'off-target' properties. We identify a novel ATP/P2RX7/K+ efflux-independent and caspase-1/8-dependent pathway for production of IL-1β in rat dendritic cells, which was absent in macrophages. Taken together, these results comprehensively establish that inflammation and autoimmunity in glomerulonephritis is independent of P2RX7 and reveals the off-target properties of drugs previously known as selective P2RX7 antagonists. Rat mononuclear phagocytes may be able to utilise an 'alternative inflammasome' pathway to produce IL-1β independently of P2RX7, which may account for the susceptibility of P2RX7 KO rats to inflammation and autoimmunity in glomerulonephritis. This article is protected by copyright. All rights reserved.

Journal article

Falcone S, Nicol T, Blease A, Randles MJ, Angus E, Page A, Tam FWK, Pusey CD, Lennon R, Potter PKet al., 2022, A novel model of nephrotic syndrome results from a point mutation in Lama5 and is modified by genetic background, Publisher: ELSEVIER SCIENCE INC, Pages: 527-540, ISSN: 0085-2538

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

Walsh M, Collister D, Zeng L, Merkel PA, Pusey CD, Guyatt G, Peh CA, Szpirt W, Ito-Hara T, Jayne DRWet al., 2022, The effects of plasma exchange in patients with-ANCA-associated vasculitis: an updated systematic review and -meta-analysis, BMJ-BRITISH MEDICAL JOURNAL, Vol: 376, ISSN: 0959-535X

Journal article

Woollard K, 2022, Chronic kidney disease mediates cardiac dysfunction associated with increased resident cardiac macrophages, BMC Nephrology, Vol: 23, Pages: 1-15, ISSN: 1471-2369

Background – The leading cause of death in end-stage kidney disease is related tocardiovascular disease. Macrophages are known to be involved in both chronic kidney disease(CKD) and heart failure, however their role in the development of cardiorenal syndrome is lessclear. We thus sought to investigate the role of macrophages in uremic cardiac disease.Methods – We assessed cardiac response in two experimental models of CKD and testedmacrophage and chemokine implication in monocytopenic CCR2-/- and anti-CXCL10 treatedmice. We quantified CXCL10 in human CKD plasma and tested the response of human iPSCderived cardiomyocytes and primary cardiac fibroblasts to serum from CKD donors. Results– We found that reduced kidney function resulted in the expansion of cardiac macrophages,in particular through local proliferation of resident populations. Influx of circulating monocytescontributed to this increase. We identified CXCL10 as a crucial factor for cardiac macrophageexpansion in uremic disease. In humans, we found increased plasma CXCL10 concentrationsin advanced CKD, and identified the production of CXCL10 in cardiomyocytes and cardiacfibroblasts. Conclusions – This study provides new insight into the role of the innate immunesystem in uremic cardiomyopathy.

Journal article

Gulati K, Edwards H, Prendecki M, Cairns TD, Condon M, Galliford J, Griffith M, Levy JB, Tam FWK, Tanna A, Pusey CD, McAdoo SPet al., 2021, Combination treatment with rituximab, low-dose cyclophosphamide and plasma exchange for severe antineutrophil cytoplasmic antibody-associated vasculitis, Kidney International, Vol: 100, Pages: 1316-1324, ISSN: 0085-2538

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis can present with life-threatening lung-kidney syndromes. However, many controlled treatment trials excluded patients with diffuse alveolar hemorrhage or severely impaired glomerular filtration rates, and so the optimum treatment in these cases is unclear. In this retrospective cohort study, we report the outcomes of 64 patients with life-threatening disease treated with a combination regimen of rituximab, low-dose intravenous cyclophosphamide, oral glucocorticoids, and plasma exchange. At entry, the median estimated glomerular filtration rate was 9 mL/min, 47% of patients required dialysis, and 52% had diffuse alveolar hemorrhage. All patients received a minimum of seven plasma exchanges, and the median cumulative doses of rituximab, cyclophosphamide, and glucocorticoid were 2, 3, and 2.6 g, respectively, at six months. A total of 94% of patients had achieved disease remission (version 3 Birmingham Vasculitis Activity Score of 0) at this time point, and 67% of patients who required dialysis recovered independent kidney function. During long-term follow-up (median duration 46 months), overall patient survival was 85%, and 69% of patients remained free from end-stage kidney disease, which compares favorably to a historic cohort with severe disease treated with a conventional induction regimen. Combination treatment was associated with prolonged B cell depletion and low rates of relapse; 87% of patients were in continuous remission at month 36. The serious infection rate during total follow-up was 0.28 infections/patient/year, suggesting that combination treatment is not associated with an enduring risk of infection. Thus, we suggest that combination immunosuppressive therapy may permit glucocorticoid avoidance and provide rapid and prolonged disease control in patients with severe ANCA-associated vasculitis.

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

Medjeral-Thomas NR, Pusey CD, 2021, New Insights into Epidemiology and Outcome of Bacterial Infection?Related Glomerulonephritis, CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, Vol: 16, Pages: 1149-1151, ISSN: 1555-9041

Journal article

Vallant N, Wolfhagen N, Sandhu B, Hamaoui K, Cook T, Pusey C, Papalois Vet al., 2021, A Comparison of Pulsatile Hypothermic and Normothermic Ex Vivo Machine Perfusion in a Porcine Kidney Model, TRANSPLANTATION, Vol: 105, Pages: 1760-1770, ISSN: 0041-1337

Journal article

Teng YKO, Pusey CD, Vaglio A, Mok CC, van Kooten Cet al., 2021, Editorial: Immune Monitoring Responses in Renal Autoimmune Diseases, FRONTIERS IN IMMUNOLOGY, Vol: 12, ISSN: 1664-3224

Journal article

Page TH, Chiappo D, Brunini F, Garnica J, Blackburn J, Dudhiya F, Prendecki M, McAdoo SP, Pusey CDet al., 2021, Danger-associated molecular pattern molecules and the receptor for advanced glycation end products enhance ANCA-induced responses, RHEUMATOLOGY, Vol: 61, Pages: 834-845, ISSN: 1462-0324

Journal article

Boharoon H, Tomlinson J, Limback-Stanic C, Gontsarova A, Martin N, Hatfield E, Meeran M, Nair R, Mendoza N, Levy J, McAdoo S, Pusey C, Wernig Fet al., 2021, A case series of patients with isolated IgG4-related hypophysitis treated with rituximab, Journal of the Endocrine Society, Vol: 4, Pages: 1-9, ISSN: 2472-1972

ContextThe acute presentation of Immunoglobulin G4 (IgG4)-related hypophysitis can be indistinguishable from other forms of acute hypophysitis and histology remains the diagnostic gold standard. The high recurrence rate necessitates long term immunosuppressive therapy. Rituximab (RTX) has been shown to be effective in systemic IgG4-related disease (IgG4-RD), but experience with isolated pituitary involvement remains limited.Case descriptionWe report three female patients with MRI findings suggestive of hypophysitis. All patients underwent transsphenoidal biopsy and fulfilled diagnostic criteria for IgG4-related hypophysitis. Treatment with GCs (GC) resulted in good therapeutic response in patients 1 and 2, but the disease recurred on tapering doses of GCs. GC treatment led to emotional lability in Patient 3 necessitating dose reduction. All three patients received RTX and Patients 2 and 3 received further courses when symptoms returned and B-cells repopulated. Patient 3 did not receive RTX until 12 months from onset of symptoms. Patient 1 was not able to have further RTX treatments due to an allergic reaction when receiving the second dose. RTX treatment resulted in sustained remission and full recovery of anterior pituitary function in Patients 1 and 2 with complete resolution of pituitary enlargement. By contrast, Patient 3 only showed symptomatic response following RTX treatment, but pituitary enlargement and hypofunction persisted.ConclusionRTX treatment for IgG4-related hypophysitis resulted in sustained remission in two patients treated early in the disease process, but only achieved partial response in a patient with chronic disease suggesting that early therapeutic intervention may be crucial to avoid irreversible changes.

Journal article

McAdoo S, Farrah TE, Prendecki M, Pusey C, Hunter R, Cairns T, Dhaun N, Lahiri Ret al., 2021, Glucocorticoid-free treatment of severe ANCA-associated vasculitis, Nephrology Dialysis Transplantation, Vol: 36, Pages: 739-742, ISSN: 0931-0509

Journal article

Farrah TE, Prendecki M, Hunter RW, Lahiri R, Cairns TD, Pusey CD, McAdoo SP, Dhaun Net al., 2021, Glucocorticoid-free treatment of severe ANCA-associated vasculitis., Nephrol Dial Transplant, Vol: 36, Pages: 739-742

Journal article

Pokidysheva EN, Seeger H, Pedchenko V, Chetyrkin S, Bergmann C, Abrahamson D, Cui ZW, Delpire E, Fervenza F, Fidler AL, Fogo AB, Gaspert A, Grohmann M, Gross O, Haddad G, Harris RC, Kashtan C, Kitching AR, Lorenzen JM, McAdoo S, Pusey CD, Segelmark M, Simmons A, Voziyan PA, Wagner T, Wüthrich RP, Zhao M-H, Boudko SP, Kistler AD, Hudson BGet al., 2021, Collagen IVα345 dysfunction in glomerular basement membrane diseases. I. Discovery of a COL4A3 variant in familial Goodpasture's and Alport diseases, Journal of Biological Chemistry, Vol: 296, ISSN: 0021-9258

Diseases of the glomerular basement membrane (GBM), such as Goodpasture's disease (GP) and Alport syndrome (AS), are a major cause of chronic kidney failure and an unmet medical need. Collagen IVα345 is an important architectural element of the GBM that was discovered in previous research on GP and AS. How this collagen enables GBM to function as a permselective filter and how structural defects cause renal failure remain an enigma. We found a distinctive genetic variant of collagen IVα345 in both a familial GP case and four AS kindreds that provided insights into these mechanisms. The variant is an 8-residue appendage at the C-terminus of the α3 subunit of the α345 hexamer. A knock-in mouse harboring the variant displayed GBM abnormalities and proteinuria. This pathology phenocopied AS, which pinpointed the α345 hexamer as a focal point in GBM function and dysfunction. Crystallography and assembly studies revealed underlying hexamer mechanisms, as described in Companion Papers II and III. Bioactive sites on the hexamer surface were identified where pathogenic pathways of GP and AS converge, and, potentially, that of diabetic nephropathy (DN). We conclude that the hexamer functions include signaling and organizing macromolecular complexes, which enable GBM assembly and function. Therapeutic modulation or replacement of α345 hexamer could therefore be a potential treatment for GBM diseases, and this knock-in mouse model is suitable for developing gene therapies.

Journal article

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

Moiseev S, Kronbichler A, Makarov E, Bulanov N, Crnogorac M, Direskeneli H, Galesic K, Gazel U, Geetha D, Guillevin L, Hruskova Z, Little MA, Ahmed A, McAdoo SP, Mohammad AJ, Moran S, Novikov P, Pusey CD, Rahmattulla C, Satrapova V, Silva J, Terrier B, Tesar V, Westman K, Jayne DRWet al., 2021, Association of venous thromboembolic events with skin, pulmonary and kidney involvement in ANCA-associated vasculitis: a multinational study, RHEUMATOLOGY, Vol: 60, Pages: 4654-4661, ISSN: 1462-0324

Journal article

Papalois V, Vallant N, Pusey C, Hamaoui K, Sandhu B, Prendecki Met al., 2021, Immunomodulatory properties of mesenchymal stromal cellscan vary in genetically modified rats, International Journal of Molecular Sciences, Vol: 22, Pages: 1-15, ISSN: 1422-0067

Mesenchymal Stromal Cells (MSC) have been shown to exhibit immuno-modulatory and regenerative properties at sites of inflammation. In solid organ transplantation (SOT), administration of MSCs might lead to an alleviation of ischemia-reperfusion injury and a reduction of rejection episodes. Previous reports have suggested ‘MSC-preconditioning’ of macrophages to be partly responsible for the beneficial effects. Whether this results from direct cell-cell interactions (e.g., MSC trans-differentiation at sites of damage), or from paracrine mechanisms, remains unclear. Immunosuppressive capacities of MSCs from donors of different age and from genetically modified donor animals, often used for in-vivo experiments, have so far not been investigated. We conducted an in vitro study to compare paracrine effects of supernatants from MSCs extracted from young and old wild-type Wystar-Kyoto rats (WKY-wt), as well as young and old WKY donor rats positive for the expression of green fluorescent protein (WKY-GFP), on bone marrow derived macrophages (BMDM). Expression levels of Mannose receptor 1 (Mrc-1), Tumor necrosis factor α (TNFα), inducible NO synthase (iNos) and Interleukin-10 (IL-10) in BMDMs after treatment with different MSC supernatants were compared by performance of quantitative PCR. We observed different expression patterns of inflammatory markers within BMDMs, depending on age and genotype of origin for MSC supernatants. This must be taken into consideration for preclinical and clinical studies, for which MSCs will be used to treat transplant patients, aiming to mitigate inflammatory and allo-responses.

Journal article

Tan PG, O'Brien J, Pusey CD, McAdoo SPet al., 2021, Validation of the ANCA renal risk score in a London cohort: potential impact of treatment on prediction outcome, KIDNEY INTERNATIONAL, Vol: 99, Pages: 488-489, ISSN: 0085-2538

Journal article

Mason J, Dattani R, Barwick T, Wardany G, Gibbons N, Morgan P, Pusey C, Tam F, Tomlinson Jet al., 2020, An international patient centred study of Retroperitoneal Fibrosis, QJM: an international journal of medicine, Vol: hcaa327, ISSN: 1460-2393

BackgroundThe impact that rare chronic disorders, such as retroperitoneal fibrosis (RPF), can have on the physical and psychological aspects of a patient’s health is poorly understood. Patient-related outcome measures and experiences provide a unique opportunity to understand the impact rare chronic disorders have on a patient’s life as well as allowing healthcare providers to compare and improve performance.AimTo understand the physical and psychosocial impact that RPF has upon peoples’ lives.DesignAn international online questionnaire was therefore created to gain insights into how patients with RPF, a rare fibro-inflammatory condition, viewed their health and experiences.MethodsAn international online questionnaire comprising 62 questions/free text options, was designed in collaboration with two patient advocates and the multi-disciplinary Renal Association Rare Disease Registry (RaDaR) RPF Group the questionnaire was anonymous and freely accessible on a GOOGLE Form online platform for 6 months.ResultsA total of 229 patients from 30 countries across 5 continents responded. Four key issues were identified; (i) pain; (ii) therapy-related side effects; (iii) lack of informed doctors/information about their condition and its management; and (iv) psychological burden. Variations in diagnosis and management are highlighted with 55% undergoing a biopsy to reach a diagnosis of RPF; 75% of patients underwent a further interventional procedure with 60% concurrently treated medically.ConclusionThis study will guide further development of clinical and academic multi-disciplinary activity and shows the importance of trying to understand the impact of rare chronic disorders on the physical and psychological aspects of a patient’s health.

Journal article

Prendecki M, McAdoo SP, Pusey CD, 2020, Is There a Role for Plasma Exchange in ANCA-Associated Vasculitis?, CURRENT TREATMENT OPTIONS IN RHEUMATOLOGY, Vol: 6, Pages: 313-324

Journal article

Moiseev S, Tervaert JWC, Arimura Y, Bogdanos DP, Csernok E, Damoiseaux J, Ferrante M, Flores-Suarez LF, Fritzler MJ, Invernizzi P, Jayne D, Jennette JC, Little MA, McAdoo SP, Novikov P, Pusey CD, Radice A, Salama AD, Savige JA, Segelmark M, Shoenfeld Y, Sinico RA, Sousa M-J, Specks U, Terrier B, Tzioufas AG, Vermeire S, Zhao M-H, Bossuyt Xet al., 2020, 2020 international consensus on ANCA testing beyond systemic vasculitis, AUTOIMMUNITY REVIEWS, Vol: 19, ISSN: 1568-9972

Journal article

Smith RM, Jones RB, Specks U, Bond S, Nodale M, Aljayyousi R, Andrews J, Bruchfeld A, Camilleri B, Carette S, Cheung CK, Derebail V, Doulton T, Forbess L, Fujimoto S, Furuta S, Gewurz-Singer O, Harper L, Ito-Ihara T, Khalidi N, Klocke R, Koening C, Komagata Y, Langford C, Lanyon P, Luqmani RA, Makino H, McAlear C, Monach P, Moreland LW, Mynard K, Nachman P, Pagnoux C, Pearce F, Peh CA, Pusey C, Ranganathan D, Rhee RL, Spiera R, Sreih AG, Tesar V, Walters G, Weisman MH, Wroe C, Merkel P, Jayne Det al., 2020, Rituximab as therapy to induce remission after relapse in ANCA-associated vasculitis, ANNALS OF THE RHEUMATIC DISEASES, Vol: 79, Pages: 1243-1249, ISSN: 0003-4967

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

Unadkat SN, Pendolino AL, Kwame I, Swift A, Pusey C, Gantous A, Andrews PJet al., 2020, Nasal reconstructive surgery for vasculitis affecting the nose: our two-centre international experience, EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY, Vol: 277, Pages: 3059-3066, ISSN: 0937-4477

Journal article

Medjeral-Thomas NR, Lawrence C, Condon M, Sood B, Warwicker P, Brown H, Pattison J, Bhandari S, Barratt J, Turner N, Cook HT, Levy JB, Lightstone L, Pusey C, Galliford J, Cairns TD, Griffith Met al., 2020, Randomized, controlled trial of tacrolimus and prednisolone monotherapy for adults with de novo minimal change disease: a multicenter, randomized, controlled trial (vol 15, pg 209, 2020), Clinical Journal of the American Society of Nephrology, Vol: 15, Pages: 1027-1027, ISSN: 1555-9041

Journal article

Prendecki M, Clarke C, Cairns T, Cook T, Roufosse C, Thomas D, Willicombe M, Pusey CD, McAdoo SPet al., 2020, Anti-glomerular basement membrane disease during the COVID-19 pandemic, Kidney International, ISSN: 0085-2538

Journal article

Moiseev S, Tervaert JWC, Arimura Y, Bogdanos D, Elena C, Damoiseaux J, Ferrante M, Flores-Suarez LF, Fritzler M, Invernizzi P, Jayne D, Jennette JC, Little M, Mcadoo SP, Novikov P, Pusey CD, Radice A, Salama AD, Savige J, Segelmark M, Shoenfeld Y, Sinico RA, De Sousa MJR, Specks U, Terrier B, Tzioufas A, Vermeire S, Zhao MH, Bossuyt Xet al., 2020, AB0501 Three cases of vertebral arteritis identified on FDG-PET in patients with suspected GCA at University of College London Hospital (UCLH), Annual European Congress of Rheumatology (EULAR), Publisher: BMJ PUBLISHING GROUP, Pages: 1549-1549, ISSN: 0003-4967

Background: Giant cell arteritis (GCA) may affect both cranial and extra-cranial vessels; where the latter occurs, it can be termed large-vessel GCA (LV-GCA). Large vessel involvement is common: histological evidence has been seen in 80% of autopsies of patients with known GCA, and imaging studies suggest large vessel involvement in over 80%1. LV-GCA is important to diagnose due to the risks of vascular complications such as occlusion and ischaemic stroke. The clinical diagnosis can be challenging, and the American College of Rheumatology (ACR) GCA classification criteria often underperform in cases of LV-GCA1. F-fluorodeoxyglucose positron emission tomography (FDG-PET) has been found to be useful in the detection of extra-cranial involvement to support the diagnosis of LV-GCA.2Objectives: To appreciate the variability in presentation of cases of LV-GCA, and to further characterise a subgroup of patients with vertebral arteritis.To explore the use of FDG-PET imaging in GCA patients in addition to or in place of traditional diagnostic tools (temporal artery ultrasound / biopsy).Methods: Through evaluation of the new GCA fast-track pathway implemented at UCLH, a subgroup of patients diagnosed with vertebral arteritis was identified. The history and presentation of these patients were analysed.Results: Three patients were diagnosed with vertebral arteritis. All three were male, Caucasian and aged over 70. All were investigated for GCA due to a history of severe headache (frontal in one, occipital in one, bi-temporal in one) with associated red flag symptoms. Two had a history of jaw claudication and visual disturbances (unilateral visual loss in one, transient diplopia in the other). Both of these patients had positive temporal artery biopsies. The third patient had no ischaemic symptoms but a strong history of prominent polymyalgic features and a positive temporal artery ultrasound. Inflammatory markers were raised in two, and normal in one, of the patients. Only one

Conference paper

Ye X, Bright R, Woollard K, Pusey CD, Duncan N, Kotanko Pet al., 2020, MONOCYTE/NEUTROPHIL: LYMPHOCYTE RATIO, C-REACTIVE PROTEIN IN THE LAST YEAR BEFORE DEATH IN DIFFERENT VINTAGE GROUPS - RESULTS FROM THE MONDO INITIATIVE, 57th ERA-EDTA Congress, Publisher: OXFORD UNIV PRESS, Pages: 1765-1765, ISSN: 0931-0509

Conference paper

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