From systemic lupus erythematosus to lupus nephritis: The evolving road to targeted therapies.

Autor: Xipell M; Department of Nephrology and Renal Transplantation, Clinic Barcelona, Spain; Reference Center for Complex Glomerular Diseases of the Spanish Health System (CSUR), Department of Medicine, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Lledó GM; Department of Autoimmune Diseases, Clínic Barcelona, Spain; Reference Center for Systemic Autoimmune Diseases of the Spanish Health System (CSUR), Department of Medicine, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain., Egan AC; Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Medicine, University of Cambridge, United Kingdom., Tamirou F; Rheumatology Department, Cliniques Universitaires Saint-Luc, Bruxelles, Belgium; Pôle de Pathologies Rhumatismales Inflammatoires et Systémiques, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Belgium., Del Castillo CS; Department of Immunology, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain., Rovira J; Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Gómez-Puerta JA; Department of Rheumatology, Clínic Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Catalonia, Spain., García-Herrera A; Department of Pathology, Clínic Barcelona, Spain; Reference Center for Complex Glomerular Diseases of the Spanish Health System (CSUR), Department of Medicine, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain., Cervera R; Department of Autoimmune Diseases, Clínic Barcelona, Spain., Kronbichler A; Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, United Kingdom., Jayne DRW; Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, United Kingdom., Anders HJ; Division of Nephrology, Department of Medicine IV, LMU University Hospital, LMU Munich, Munich, Germany., Houssiau F; Vasculitis and Lupus Service, Addenbrooke's Hospital, Cambridge, United Kingdom; Department of Medicine, University of Cambridge, United Kingdom., Espinosa G; Department of Autoimmune Diseases, Clínic Barcelona, Spain; Reference Center for Systemic Autoimmune Diseases of the Spanish Health System (CSUR), Department of Medicine, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain. Electronic address: gespino@clinic.cat., Quintana LF; Department of Nephrology and Renal Transplantation, Clinic Barcelona, Spain; Reference Center for Complex Glomerular Diseases of the Spanish Health System (CSUR), Department of Medicine, University of Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Electronic address: lfquinta@clinic.cat.
Jazyk: angličtina
Zdroj: Autoimmunity reviews [Autoimmun Rev] 2023 Oct; Vol. 22 (10), pp. 103404. Date of Electronic Publication: 2023 Aug 03.
DOI: 10.1016/j.autrev.2023.103404
Abstrakt: Systemic lupus erythematosus is a chronic autoimmune disease characterized by loss of tolerance against nuclear and cytoplasmic self-antigens, induction of immunity and tissue inflammation. Lupus nephritis (LN), the most important predictor of morbidity in SLE, develops in almost 30% of SLE patients at disease onset and in up to 50-60% within the first 10 years. Firstly, in this review, we put the pathogenic mechanisms of the disease into a conceptual frame, giving emphasis to the role of the innate immune system in this loss of self-tolerance and the induction of the adaptive immune response. In this aspect, many mechanisms have been described such as dysregulation and acceleration of cell-death pathways, an aberrant clearance and overload of immunogenic acid-nucleic-containing debris and IC, and the involvement of antigen-presenting cells and other innate immune cells in the induction of this adaptive immune response. This result in a clonal expansion of autoreactive lymphocytes with generation of effector T-cells, memory B-cells and plasma cells that produce autoantibodies that will cause kidney damage. Secondly, we review the immunological pathways of damage in the kidney parenchyma, initiated by autoantibody binding and immune complex deposition, and followed by complement-mediated microvascular injury, activation of kidney stromal cells and the recruitment of leukocytes. Finally, we summarize the rationale for the treatment of LN, from conventional to new targeted therapies, focusing on their systemic immunologic effects and the minimization of podocytary damage.
Competing Interests: Declaration of Competing Interest MX received lecture fees from GSK. JGP discloses honoraria from AstraZeneca, Abbvie, Galápagos, GSK, Janssen, ElyLilly, Pfizer, and Advisory for Galapagos and Sanofi. RC discloses honoraria and advisory from AstraZeneca, Celgene, GSK, Janssen, ElyLilly, Pfizer, UCB and Rubió. AK discloses consulting from CSL Vifor, Otsuka, Catalyst Biosciences, Walden Biosciences, GSK and Delta4. DJ received consultancy fees from Astra-Zeneca, BMS, Boehringer-Ingelheim, Chemocentryx, GSK, NICE, Novartis, Otsuka, Roche/Genentech, Takeda, UCB&Vifor; lecture fees from Amgen, Kessai, Vifor; and has stock options from Aurinia. Also, he received research grants from GSK, Roche/Genentech, EU, MRC, NIHR, Versus Arthritis. HJA received consultancy and lecture fees from Otsuka, GSK, Novartis, Janssen, AstraZeneca, Roche, and Vifor. FH received grants from GSK and Roche. GE received research funding from GSK and payments for presentations and advice from GSK and Otsuka. LFQ received honoraria from GSK, Otsuka, CSL Vifor and is on the advisory board of GSK, Otsuka, Alexion, Novartis and CSL Vifor. GMLL, FT, AE, CS, JR and AGH have nothing to disclose.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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