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Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management.

Drug-induced thrombotic microangiopathy (DITMA) represents 10%-13% of all thrombotic microangiopathy (TMA) cases and about 20%-30% of secondary TMAs, just behind pregnancy-related and infection-related forms. Although the list of drugs potentially involved as causative for TMA are rapidly increasing, the scientific literature on DITMA is quite scarce (mostly as individual case reports or little case series), leading to poor knowledge of pathophysiological mechanisms and clinical management. In this review, we focused on these critical aspects regarding DITMA. We provided an updated list of TMA

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… Complement C5 inhibition reverses bleomycin-induced thrombotic microangiopathy. Clin. Kidney J. 14, 1275–1276. 10.1093/ckj/sfaa101 Schwartz J., Padmanabhan A., Aqui N., Balogun R. A., Connelly-Smith L., Delaney M., et al. (2016). …

An Update on Current Therapeutic Options in IgA Nephropathy.

Immunoglobulin A nephropathy (IgAN) remains the leading cause of primary glomerular disease worldwide. Outcomes are poor with high rates of progressive chronic kidney disease and kidney failure, which contributes to global healthcare costs. Although this disease entity has been described, there were no disease-specific treatments until recently, with the current standard of care focusing on optimal supportive measures including lifestyle modifications and optimization of the renin-angiotensin-aldosterone blockade. However, with significant advances in the understanding of the pathogenesis of I

Chemotherapy-Associated Thrombotic Microangiopathy.

Thrombotic microangiopathy (TMA) is a syndrome of microangiopathic hemolytic anemia and thrombocytopenia with end-organ dysfunction. Although the advent of plasma exchange, immunosuppression, and complement inhibition has improved morbidity and mortality for primary TMAs, the management of secondary TMAs, particularly drug-induced TMA, remains less clear. TMA related to cancer drugs disrupts the antineoplastic treatment course, increasing the risk of cancer progression. Chemotherapeutic agents such as mitomycin-C, gemcitabine, and platinum-based drugs as well as targeted therapies such as anti

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… C5 has improved mortality and renal recovery in aHUS. 89 Its success in aHUS has motivated its use in chemotherapy-associated TMA. … Complement C5 inhibition reverses bleomycin-induced thrombotic microangiopathy. Clin Kidney J. 2021;14(4):1275–1276. doi: 10.1093/ckj/sfaa101 26. Jackson AM. Thrombotic microangiopathy and renal failure associated with antineoplastic chemotherapy. …

Global perspectives on lupus nephritis: a review of clinical trials and therapeutic innovations.

BACKGROUND AND OBJECTIVES: Lupus nephritis (LN) remains a leading cause of morbidity and mortality in systemic lupus erythematosus (SLE). Although recent years have witnessed the approval of several targeted therapies, achieving long-term, drug-free remission remains challenging. This commentary evaluates the global landscape of interventional LN clinical trials from 2001 to 2026 to identify emerging trends and strategic gaps in drug development. METHODS: We analyzed 200 interventional pharmacological trials retrieved from three major global registries: ClinicalTrials.gov, Chinadrugtrials.org

Targeting autoimmune mechanisms by precision medicine in Myasthenia Gravis.

Myasthenia Gravis (MG) is a chronic disabling autoimmune disease caused by autoantibodies to the neuromuscular junction (NMJ), characterized clinically by fluctuating weakness and early fatigability of ocular, skeletal and bulbar muscles. Despite being commonly considered a prototypic autoimmune disorder, MG is a complex and heterogeneous condition, presenting with variable clinical phenotypes, likely due to distinct pathophysiological settings related with different immunoreactivities, symptoms' distribution, disease severity, age at onset, thymic histopathology and response to therapies. Cur

The Complosome: An Emerging Intracellular Complement Network in Cancer Development and Therapy.

The complement system is traditionally recognized as a major effector of innate immunity, essential for pathogen clearance, inflammation and the maintenance of tissue homeostasis. In recent years, however, its role in cancer has been substantially redefined. Beyond its canonical extracellular activity, complement has emerged as a multifaceted regulator of tumor biology, acting not only within the tumor microenvironment but also intracellularly through the recently described intracellular complement system (complosome). While extracellular complement primarily shapes immune responses and the tu

New and Emerging Biological Therapies for Myasthenia Gravis: A Focussed Review for Clinical Decision-Making.

Myasthenia gravis (MG) is a rare autoimmune disease characterised by exertion-induced muscle weakness that can lead to potentially life-threatening myasthenic crises. Detectable antibodies are directed against specific postsynaptic structures of the neuromuscular junction. MG is a chronic condition that can be improved through therapies, but to date, not cured. Standard treatment has been unchanged for decades and includes symptomatic treatment with acetylcholine-esterase inhibitors and disease-modifying treatment with steroids, steroid-sparing immunosuppressants and thymectomy. Overall, a rel

Editorial: The Role of Complement in Health and Disease.

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Схемы демиэлизации моторного нерва и их прогнозируемое значение в мультифокальной моторной нейропатии.

Мультифокальная моторная нейропатия (ММН) представляет собой редкую иммунопосредованную нейропатию, характеризующуюся участием моторного нерва и, как правило, хорошей реакцией на иммуноглобулин внутривенно. Однако подгруппа пациентов демонстрирует плохое или отсутствующее лечение и более быстрый курс лечения. Мы стремимся охарактеризовать клинические, лабораторные и электрофизиологические характеристики, связанные с реакцией IVIg в MMN в течение последующего периода до 20 Были ретроспективно проанализированы методы Thirten, отвечающие диагностическим критериям для определенного MMN. Была прове

Research Progress in Pharmacological Targeted Therapy for Myasthenia Gravis.

Myasthenia gravis (MG) is a disorder of neuromuscular junction transmission that is mediated by autoantibodies and depends on T cell help, causing fatigable muscle weakness. Limitations of conventional first-line treatments, including long-term adverse effects and inadequate control of refractory disease, have driven targeted therapy to the forefront of MG research. This narrative review summarizes second-line and later-line targeted biological and cellular therapies, covering agents directedat B and T cells, complement inhibitors, neonatal Fc receptor (FcRn) antagonists and cytokine inhibitor

Genetic and Functional Evidence of Complement Dysregulation in Multiple Myeloma Patients with Carfilzomib-Induced Thrombotic Microangiopathy Compared to Controls.

BACKGROUND: Carfilzomib, an irreversible proteasome inhibitor approved for the treatment of relapsed/refractory Multiple Myeloma (MM) has been associated with Thrombotic Microangiopathy (TMA). Several pathogenetic mechanisms of carfilzomib-induced TMA have been proposed; however, recently, there has been a shift of focus on the potential contribution of complement dysregulation. Our aim was to explore whether patients with carfilzomib-induced TMA harbor germline variants of complement-related genes, which have been characterized as risk factors for TMA. METHODS: We retrospectively recruited c

Novel Immunotherapies for Myasthenia Gravis.

Myasthenia gravis (MG), a prototype autoimmune neurological disease, had its therapy centred on corticosteroids, non-steroidal broad-spectrum immunotherapy and cholinesterase inhibitors for several decades. Treatment-refractory MG and long-term toxicities of the medications have been major concerns with the conventional therapies. Advances in the immunology and pathogenesis of MG have ushered in an era of newer therapies which are more specific and efficacious. Complement inhibitors and neonatal Fc receptor blockers target disease-specific pathogenic mechanisms linked to myasthenia and have pr

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… Zilucoplan: an investigational complement C5 inhibitor for the treatment of acetylcholine receptor autoantibody–positive generalized myasthenia gravis. Expert Opin Investig Drugs . 2021;30(5):483–493. doi: 10.1080/13543784.2021.1897567 49. Howard JF, Nowak RJ, Wolfe GI, et al. …

Beneath the surface in autoimmune hemolytic anemia: pathogenetic networks, therapeutic advancements and open questions.

In recent years, the pathophysiologic framework of autoimmune hemolytic anemias (AIHAs) has evolved considerably, extending beyond the simplistic paradigm of antibody-mediated red blood cell (RBC) destruction, which is now recognized as a downstream consequence of a broader immune dysregulation. AIHA is fundamentally orchestrated by a complex interplay between innate and adaptive immune components, including autoreactive B and T lymphocytes, macrophages, and the reticuloendothelial system. Central to disease pathogenesis are two interrelated mechanisms: clonal B-cell expansion with autoantibod

The burden of illness of patients with paroxysmal nocturnal haemoglobinuria receiving C5 inhibitors in France, Germany and the United Kingdom: Patient-reported insights on symptoms and quality of life.

OBJECTIVES: To assess the clinical, humanistic and economic burden of paroxysmal nocturnal haemoglobinuria (PNH) among C5 inhibitor (C5i)-treated patients with PNH. METHODS: This was a web-based, cross-sectional survey (01FEB2021-31MAR2021) of adults with PNH treated with eculizumab (France, Germany, United Kingdom) or ravulizumab (Germany). Self-reported outcomes included: patient characteristics; patient-reported symptoms; and standardised patient-reported outcomes (e.g. Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, European Organization for Research and Treatment of Can

Polypharmacology: new drugs in 2023-2024.

Polypharmacology is an emerging approach to drug design and development that involves the use of multi-target-directed ligands (MTDLs), agents capable of interacting with multiple biological targets simultaneously. The effective treatment of chronic and multifactorial conditions, driven by the dysregulation of multiple interconnected pathways, such as cancer, autoimmune and metabolic disorders, cardiovascular and neurodegenerative diseases, is one of the most substantial challenges in contemporary pharmacology. 'Traditional' single-target-based treatment frequently shows limited effectiveness,

ISN Nexus 2016 Symposia: Translational Immunology in Kidney Disease—The Berlin Roadmap

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Structure and function of therapeutic antibodies approved by the US FDA in 2025.

In 2025, the 50th anniversary of the invention of hybridoma technology, the United States Food and Drug Administration (US FDA) approved a total of 44 new molecular entities (NMEs), of which 10 were therapeutic antibody-based molecules. Additionally, the US FDA approved 31 small molecules (of which one was a peptide), and 3 new nonantibody therapeutic proteins, but no new chimeric antigen receptor (CAR)-T-cell therapeutics. Of the new antibody-based biologics, two were antibody-drug conjugates, one was a T-cell engager-bispecific antibody, two were Fc-modified, half-life extended antibodies, a

Contemporary Monoclonal Antibody Utilization in Glomerular Diseases.

Therapeutic monoclonal antibodies (MAbs) have been one of the fastest growing drug classes in the past 2 decades and are indicated in the treatment of cancer, autoimmune disorders, solid organ transplantation, and glomerular diseases. The Food and Drug Administration has approved 100 MAbs between 1986 and 2021, and MAbs account for 20% of Food and Drug Administration's new drug approval every year. MAbs are preferred over traditional immunosuppressive agents because of their high specificity, reduced number of drug-drug interactions, and low toxicity, which make them a prime example of persona

Biocompatibility in hemodialysis: artificial membrane and human blood interactions.

Hemodialysis, a cornerstone therapy for chronic kidney disease, represented a crucial advance in the evolution of artificial organs. While its success is largely due to its efficiency in removing uremic toxins, an equally important challenge is to uphold the primum non nocere principle by minimizing the harmful effects of membrane-blood interactions. This review examines the complex mechanisms and key interactions underlying membrane biocompatibility, including complement activation, inflammation, and coagulation disturbances, paving the way for their clinical implications. We also summarize r

Benefit and danger from immunotherapy in myasthenia gravis.

In the last years, significant advances have improved the knowledge of myasthenia gravis (MG) immunopathogenesis and have enabled to realize new molecules with a selective action targeting compounds of the immunological system. This review discusses emerging treatments for MG, including complement inhibitors, neonatal Fc receptor targeting agents, and B cell interfering drugs, focusing on benefit and danger. In the second section of the review, several related adverse events of immunotherapy, including MGonset, are debated.