Review
Medicine, General & Internal
Salem Almaani, Lynn A. Fussner, Sergey Brodsky, Alexa S. Meara, David Jayne
Summary: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of small vessel vasculitides characterized by granulomatous and neutrophilic tissue inflammation, often associated with the production of antibodies that target neutrophil antigens. AAV involves multiple organ systems clinically, including the lungs, kidneys, skin, and nervous system. The prognosis of AAV has significantly improved due to advances in understanding its pathogenesis and treatment options.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Oncology
Maria Prendecki, Kavita Gulati, Tabitha Turner-Stokes, Gurjeet Bhangal, Derick Chiappo, Kevin Woollard, H. Terence Cook, Frederick W. K. Tam, Candice Roufosse, Charles D. Pusey, Stephen P. McAdoo
Summary: Experimental autoimmune vasculitis (EAV) induced by myeloperoxidase (MPO) immunization in susceptible rat strains can be augmented by sub-nephritogenic dose of nephrotoxic serum (NTS) containing heterologous antibodies, leading to increased severity of glomerulonephritis with important features of human disease. The pauci-immune glomerulonephritis is strictly dependent on autoimmunity to MPO, showcasing potential for studying glomerular leukocyte behavior and novel therapeutics in antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV).
JOURNAL OF PATHOLOGY
(2021)
Article
Immunology
Desiree Tampe, Peter Korsten, Philipp Stroebel, Samy Hakroush, Bjoern Tampe
Summary: This study systematically analyzed sex differences in patients with AAV and biopsy-proven ANCA GN, finding that female patients presented at an older age with more joint involvement and exhibited specific sex differences in laboratory parameters and histopathological findings. There were fewer associations between clinical, laboratory parameters, and histopathological findings in females compared to males, indicating the importance of considering sex differences in AAV, particularly ANCA GN.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Urology & Nephrology
Uwe Jerke, Claudia Eulenberg-Gustavus, Anthony Rousselle, Paul Nicklin, Stefan Kreideweiss, Marc A. Grundl, Peter Eickholz, Katrin Nickles, Adrian Schreiber, Brice Korkmaz, Ralph Kettritz
Summary: CatC inhibition may be an effective adjunctive treatment for PR3-AAV, reducing neutrophil-induced endothelial cell damage.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Immunology
Samy Hakroush, Desiree Tampe, Philipp Stroebel, Peter Korsten, Bjoern Tampe
Summary: This study analyzed kidney biopsies of patients with ANCA GN and found that different types of immune cell infiltrates were associated with clinicopathological findings, particularly neutrophilic infiltrates were linked to glomerular necrosis and severe kidney injury, while eosinophilic infiltrates were associated with kidney injury and inflammation independent of glomerular lesions, suggesting distinct roles in inflammation and damage in ANCA GN. Plasma cell infiltrates and mononuclear cell infiltrates were also correlated with specific histopathological lesions and disease outcomes. The study suggests that different pathogenic mechanisms may be involved in MPO-ANCA versus PR3-ANCA GN, and may lead to potential new therapeutic targets for specific ANCA subtypes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Desiree Tampe, Peter Korsten, Philipp Stroebel, Samy Hakroush, Bjoern Tampe
Summary: Proteinuria in ANCA GN is correlated with distinct clinicopathological characteristics, such as MPO subtype, MPA diagnosis, and severe kidney function deterioration. The presence of proteinuria is most prominent in ANCA GN with sclerotic class and high ANCA renal risk score, indicating specific renal involvement rather than systemic disease activity.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, General & Internal
Samy Hakroush, Ingmar Alexander Kluge, Philipp Stroebel, Peter Korsten, Desiree Tampe, Bjorn Tampe
Summary: This study describes active and chronic tubulointerstitial lesions in ANCA GN subtypes using systematic scoring analogous to the Banff scoring system, as well as clinical and laboratory findings. MPO-ANCA GN is associated with more severe kidney function deterioration, increased proteinuria, and a decreased fraction of normal glomeruli. The research provides new insights into pathophysiology and differences in clinical presentation, potentially leading to more precise treatment regimens for ANCA GN subtypes.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Transplantation
Laura S. van Dam, Ebru Dirikgil, Edwin W. Bredewold, Argho Ray, Jaap A. Bakker, Cees van Kooten, Ton J. Rabelink, Yoe K. Onno Teng
Summary: In AAV patients treated with RTX, ANCA and B-cell status were predictive of the majority of relapses, and specifically their absence strongly predicted a relapse-free status. Monitoring ANCA and B-cell levels could guide therapeutic decisions to prevent relapses in these patients.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2021)
Article
Biochemistry & Molecular Biology
Samy Hakroush, Ingmar Alexander Kluge, Eva Baier, Desiree Tampe, Bjoern Tampe
Summary: This study explores the localization of C4 deposits in patients with ANCA-associated renal vasculitis and its association with survival and distinct histopathological lesions. The findings provide valuable insights into the disease and offer potential markers for personalized treatment approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, General & Internal
Precil Diego Miranda de Menezes Neves, Lucas Braga Mota, Cristiane Bitencourt Dias, Luis Yu, Viktoria Woronik, Livia Barreira Cavalcante, Denise Maria Avancini Costa Malheiros, Lecticia Barbosa Jorge
Summary: The article reported a case of methimazole-induced ANCA-associated vasculitis leading to rapidly progressive glomerulonephritis. The patient presented with symptoms such as weight loss, fatigue, and alveolar hemorrhage, and was diagnosed with pauci-immune crescentic glomerulonephritis based on examination and renal biopsy.
Article
Immunology
Dario Roccatello, Savino Sciascia, Stefano Murgia, Giacomo Quattrocchio, Michela Ferro, Emanuele De Simone, Carla Naretto, Antonella Barreca, Andrea Sammartino, Daniela Rossi, Roberta Fenoglio
Summary: The study assessed the safety and efficacy of an intensified B-cell depletion therapy (IBCDT) in severely affected AAV patients. The results showed that IBCDT had the same efficacy as the conventional therapy with CYC plus AZA, while reducing the drug-related side effects.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Matic Bosnjak, Zeljka Veceric-Haler, Emanuela Bostjancic, Nika Kojc
Summary: This study aims to identify the intrarenal miRNA expression profile in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) patients and explore potential candidate-specific miRNAs. Analysis revealed 17 miRNAs that can differentiate AAV patients from healthy and inflammatory controls, some of which are related to cytokines involved in AAV pathogenesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Adam D. Morris, Daniel L. D. Freitas, Kassio M. G. Lima, Lauren Floyd, Mark E. Brady, Ajay P. Dhaygude, Anthony W. Rowbottom, Francis L. Martin
Summary: This study evaluated the application of machine learning and Raman spectroscopy for the automated computational detection of disease activity in ANCA-associated glomerulonephritis. The results showed that spectral data from tissue samples were able to accurately discriminate disease activity, while corresponding spectrochemical changes in paired urine samples were limited.
Review
Immunology
David Massicotte-Azarniouch, Carolina A. Herrera, J. Charles Jennette, Ronald J. Falk, Meghan E. Free
Summary: The pathogenic process in ANCA vasculitis is mainly driven by the inflammatory environment produced by ANCA-triggered neutrophil activation, leading to tissue necrosis. Genetic and epigenetic alterations exacerbate immune homeostasis disturbances, promoting ANCA formation. Current therapies targeting crucial steps in this process are being developed to address the autoimmune process in a tailored manner.
SEMINARS IN IMMUNOPATHOLOGY
(2022)
Article
Multidisciplinary Sciences
Juan Irure-Ventura, Lara Belmar-Vega, Gema Fernandez-Fresnedo, Elena Gonzalez-Lopez, Carolina Castro-Hernandez, Emilio Rodrigo-Calabia, Milagros Heras-Vicario, Juan Carlos Ruiz San Millan, Marcos Lopez-Hoyost
Summary: An increase in the development of ANCA-associated vasculitis (AAV) has been observed in 2021, with most cases occurring after SARS-CoV-2 vaccination, particularly the second dose. The kidneys and respiratory tracts are the main organs affected.
Editorial Material
Urology & Nephrology
Kate J. Robson, A. Richard Kitching
Summary: This paper discusses the risk factors for recurrent membranous nephropathy after transplantation, finding that genetics of both the autoantigen and donor HLA are important determinants of the risk of recurrent disease in the graft.
KIDNEY INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Elena N. Pokidysheva, Harald Seeger, Vadim Pedchenko, Sergei Chetyrkin, Carsten Bergmann, Dale Abrahamson, Zhao Wei Cui, Eric Delpire, Fernando C. Fervenza, Aaron L. Fidler, Agnes B. Fogo, Ariana Gaspert, Maik Grohmann, Oliver Gross, George Haddad, Raymond C. Harris, Clifford Kashtan, A. Richard Kitching, Johan M. Lorenzen, Stephen McAdoo, Charles D. Pusey, Marten Segelmark, Alicia Simmons, Paul A. Voziyan, Timo Wagner, Rudolf P. Wuethrich, Ming-Hui Zhao, Sergei P. Boudko, Andreas D. Kistler, Billy G. Hudson
Summary: A unique genetic variant of collagen IV alpha 345 was discovered in familial cases of Goodpasture's disease and Alport syndrome, leading to GBM abnormalities and proteinuria in a knock-in mouse model. Crystallography and assembly studies revealed underlying mechanisms of the hexamer, which could potentially be targeted for therapeutic interventions in GBM diseases.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Urology & Nephrology
Poh-Yi Gan, Jonathan Dick, Kim M. O'Sullivan, Virginie Oudin, Anne Cao Le, Daniel Koo Yuk Cheong, Raymond Shim, Maliha Alikhan, A. Richard Kitching, Joshua D. Ooi, Stephen R. Holdsworth
Summary: In a mouse model of MPO-AAV, treatment with anti-CD20 mAb increased the numbers and immunomodulatory capacity of MPO-specific T regulatory cells (Tregs) and attenuated T cell-mediated and humoral anti-MPO autoimmunity and GN. Anti-CD20 mAb more rapidly induced protective anti-MPO Treg-mediated immunomodulation by inducing apoptosis of B cells, suggesting a novel pathway for therapy in T cell-mediated autoimmunity.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2021)
Article
Urology & Nephrology
Simon A. Carter, Charlotte Logeman, Martin Howell, Dan Cattran, Liz Lightstone, Arvind Bagga, Sean J. Barbour, Jonathan Barratt, John Boletis, Dawn J. Caster, Rosanna Coppo, Fernando C. Fervenza, Jurgen Floege, Michelle A. Hladunewich, Jonathan J. Hogan, A. Richard Kitching, Richard A. Lafayette, Ana Malvar, Jai Radhakrishnan, Brad H. Rovin, Nicole Scholes-Robertson, Hernan Trimarchi, Hong Zhang, Yeoungjee Cho, Louese Dunn, Debbie S. Gipson, Adrian Liew, Benedicte Sautenet, Andrea K. Viecelli, David Harris, David W. Johnson, Angela Yee-Moon Wang, Armando Teixeira-Pinto, Stephen I. Alexander, Adam Martin, Allison Tong, Jonathan C. Craig
Summary: A consensus-derived set of critically important outcomes for treatment decision-making in glomerular disease trials was established through an international Delphi survey, involving patients, caregivers, and health professionals. Key outcomes identified included the need for dialysis or transplant, kidney function, death, cardiovascular disease, remission-relapse, and life participation, with variations in importance between patients/caregivers and health care professionals. Thematic analysis revealed four main reasons driving priorities in outcome importance.
KIDNEY INTERNATIONAL
(2021)
Article
Rheumatology
Maliha A. Alikhan, Juli Jaw, Lani R. Shochet, Kate J. Robson, Joshua D. Ooi, Elisabeth Brouwer, Peter Heeringa, Stephen R. Holdsworth, A. Richard Kitching
Summary: The study found that cellular immunity to MPO increases with age in mice, which may contribute to the increased incidence and severity of AAV in older individuals.
Article
Urology & Nephrology
Simon A. Carter, Liz Lightstone, Dan Cattran, Allison Tong, Arvind Bagga, Sean J. Barbour, Jonathan Barratt, John Boletis, Dawn J. Caster, Rosanna Coppo, Fernando C. Fervenza, Jurgen Floege, Michelle A. Hladunewich, Jonathan J. Hogan, A. Richard Kitching, Richard A. Lafayette, Ana Malvar, Jai Radhakrishnan, Brad H. Rovin, Nicole Scholes-Robertson, Hernan Trimarchi, Hong Zhang, Samaya Anumudu, Yeoungjee Cho, Talia Gutman, Emma O'Lone, Andrea K. Viecelli, Eric Au, Karolis Azukaitis, Amanda Baumgart, Amelie Bernier-Jean, Louese Dunn, Martin Howell, Angela Ju, Charlotte Logeman, Melissa Nataatmadja, Benedicte Sautenet, Ankit Sharma, Jonathan C. Craig
Summary: The study established core outcomes for trials in adults with glomerular disease through two workshops, including limiting disease progression, stability and control, and ensuring universal relevance. Future work is needed to establish core measures for each domain, with funders and regulators playing a central role in the uptake of the core outcome set in trials.
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Editorial Material
Pediatrics
Tania Hardja Sulaksana, Arthur Richard Kitching, Justin J. Brown, Peter Gowdie
JOURNAL OF PAEDIATRICS AND CHILD HEALTH
(2022)
Article
Urology & Nephrology
Simon A. Carter, Claris Teng, Talia Gutman, Charlotte Logeman, Dan Cattran, Liz Lightstone, Arvind Bagga, Sean J. Barbour, Jonathan Barratt, John Boletis, Dawn J. Caster, Rosanna Coppo, Fernando C. Fervenza, Jurgen Floege, Michelle A. Hladunewich, Jonathan J. Hogan, A. Richard Kitching, Richard A. Lafayette, Ana Malvar, Jai Radhakrishnan, Brad H. Rovin, Nicole Scholes-Robertson, Hernan Trimarchi, Hong Zhang, Karolis Azukaitis, Yeoungjee Cho, Andrea K. Viecelli, Louese Dunn, David Harris, David W. Johnson, Peter G. Kerr, Paul Laboi, Jessica Ryan, Jenny Shen, Lorena Ruiz, Angela Yee-Moon Wang, Achilles Hoi Kan Lee, Samuel Fung Ka Shun, Matthew Ka-Hang Tong, Armando Teixeira-Pinto, Martin Wilkie, Stephen Alexander, Jonathan C. Craig, Adam Martin, Allison Tong
Summary: Patients with glomerular disease and their care partners emphasize the importance of autonomy and disease ownership, as well as the stability of their health and supportive relationships for self-management. While facing overwhelming treatment burdens, patients still strive for stability and normalcy through social support and positive health approaches.
KIDNEY INTERNATIONAL REPORTS
(2022)
Editorial Material
Urology & Nephrology
Richard Kitching
KIDNEY INTERNATIONAL
(2022)
Editorial Material
Urology & Nephrology
Lani Shochet, A. Richard Kitching
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sharon L. Ford, Kim M. O'Sullivan, A. Richard Kitching, Stephen R. Holdsworth, Poh Yi Gan, Shaun A. Summers
Summary: This study investigates the role of Toll-like receptor 9 (TLR9) in murine experimental anti-MPO glomerulonephritis. TLR9 stimulation enhances dendritic cell activation, promotes systemic anti-MPO autoimmunity and T cell recall responses, and exacerbates kidney injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Transplantation
Paola Romagnani, A. Richard Kitching, Nelson Leung, Hans-Joachim Anders
Summary: Glomerulonephritis (GN) is a diverse group of immune-mediated disorders, which cannot be properly classified or treated based on histological patterns alone. To overcome this problem, a new classification system is proposed that considers disease category, immunological activity, and chronicity, which will guide the therapeutic approach.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Article
Transplantation
Balazs Odler, Johanna Tieu, Katharina Artinger, Michael Chen-Xu, Laurent Arnaud, Richard A. Kitching, Benjamin Terrier, Jens Thiel, Maria C. Cid, Alexander R. Rosenkranz, Andreas Kronbichler, David R. W. Jayne
Summary: In recent decades, advancements in understanding molecular pathways have greatly impacted the treatment of autoimmune diseases, although the development of new drugs for immune-mediated kidney diseases has lagged behind. Abnormalities in adaptive and innate immunity, as well as shared inflammatory pathways, play important roles in these diseases. Understanding these mechanisms provides new insights for developing treatments for immune-mediated kidney diseases.
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2023)
Review
Immunology
Hans-Joachim Anders, A. Richard Kitching, Nelson Leung, Paola Romagnani
Summary: 'Glomerulonephritis' (GN) refers to a group of immune-mediated disorders characterized by inflammation of the kidney's filtration units. Current classification is based on histopathological lesion patterns, but these patterns do not align well with the diverse pathological mechanisms and do not guide optimal therapy. Instead, a proposed immunopathogenesis-based classification groups GN disorders into five categories, allowing for more targeted and effective treatments.
NATURE REVIEWS IMMUNOLOGY
(2023)
Article
Cell Biology
Simon H. Jiang, Sevcan Mercan, Ilenia Papa, Max Moldovan, Giles D. Walters, Mark Koina, Mitali Fadia, Maurice Stanley, Tom Lea-Henry, Amelia Cook, Julia Ellyard, Brendan McMorran, Madhivanan Sundaram, Russell Thomson, Pablo F. Canete, Wendy Hoy, Holly Hutton, Monika Srivastava, Kathryn McKeon, Inigo de la Rua Figueroa, Ricard Cervera, Raquel Faria, Sandra D'Alfonso, Mariele Gatto, Vicki Athanasopoulos, Matthew Field, John Mathews, Eun Cho, Thomas D. Andrews, A. Richard Kitching, Matthew C. Cook, Marta Alarcon Riquelme, Melanie Bahlo, Carola G. Vinuesa
Summary: An intronic deletion in the VANGL1 gene was identified to be associated with nephritis in SLE patients and found at increased frequency in an indigenous population with higher rates of kidney disease. Hemizygosity of Vangl1 in mice resulted in IgA and IgG deposition in the kidney, suggesting a preventative role of Vangl1 in Ig deposits in the kidney.
CELL REPORTS MEDICINE
(2021)
