ArticleImmunology2015
C5a alters blood-brain barrier integrity in a human in vitro model of systemic lupus erythematosus.
Article in Immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Therapeutic Targeting of the Complement System: From Rare Diseases to Pandemics.Pharmacological reviews · 2021Pooled it
- Article
- Intestinal and Blood-Brain Barrier Dysfunction in Lupus: Emerging Mechanisms and Modulation by Cinnamon.Molecules (Basel, Switzerland) · 2026Review
- Immunopathogenesis of neuropsychiatric systemic lupus erythematosus: current insights into inflammatory and thrombotic pathways.Journal of neuroinflammation · 2026Review
- Shifting From Systemic to Precision-Targeted Complement Therapies: Opportunities and Hurdles.European journal of immunology · 2026Review
- Complement in brain and eye disease: shared mechanisms, convergent pathologies, and common therapeutic opportunities.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- Brain neurovascular unit in response to intra- and extra-central nervous system cancers: implications, mechanisms, and challenges.Cancer cell international · 2025Review
- Emerging role of complement system in the induction of neuroinflammation in adenylosuccinate lyase deficiency disorder.Brain, behavior, & immunity - health · 2025Review
- Knowing the enemy: strategic targeting of complement to treat Alzheimer disease.Nature reviews. Neurology · 2025Review
- Complement System and Adhesion Molecule Skirmishes in Fabry Disease: Insights into Pathogenesis and Disease Mechanisms.International journal of molecular sciences · 2024Review
- NX210c drug candidate peptide strengthens mouse and human blood-brain barriers.Fluids and barriers of the CNS · 2024Article
- Diagnosis and Management of Pediatric Neuropsychiatric Systemic Lupus Erythematosus: An Update.Paediatric drugs · 2024Review
- Implications of Inflammatory Processes on a Developing Central Nervous System in Childhood-Onset Systemic Lupus Erythematosus.Arthritis & rheumatology (Hoboken, N.J.) · 2024Review
- Choroid plexus and perivascular space enlargement in neuropsychiatric systemic lupus erythematosus.Molecular psychiatry · 2024Article
- Exploring Pro-Inflammatory Immunological Mediators: Unraveling the Mechanisms of Neuroinflammation in Lysosomal Storage Diseases.Biomedicines · 2023Review
- Complement Activation Products in Patients with Chronic Schizophrenia.Journal of clinical medicine · 2023Article
- Complementing Testicular Immune Regulation: The Relationship between Sertoli Cells, Complement, and the Immune Response.International journal of molecular sciences · 2023Review
- Targeting the Complement-Sphingolipid System in COVID-19 and Gaucher Diseases: Evidence for a New Treatment Strategy.International journal of molecular sciences · 2022Review
- Progress in the Pathogenesis and Treatment of Neuropsychiatric Systemic Lupus Erythematosus.Journal of clinical medicine · 2022Review
- Psychopathology and Stem Cell Mobilization in Ultra-High Risk of Psychosis and First-Episode Psychosis Patients.International journal of environmental research and public health · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The blood-brain barrier (BBB) plays a crucial role in brain homeostasis, thereby maintaining the brain environment precise for optimal neuronal function. Its dysfunction is an intriguing complication of systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disorder where neurological complications occur in 5-50% of cases and is associated with impaired BBB integrity. Complement activation occurs in SLE and is an important part of the clinical profile. Our earlier studies demonstrated that C5a generated by complement activation caused the loss of brain endothelial layer integrity in rodents. The goal of the current study was to determine the translational potential of these studies to a human system. To assess this, we used a two dimensional in vitro BBB model constructed using primary human brain microvascular endothelial cells and astroglial cells, which closely emulates the in vivo BBB allowing the assessment of BBB integrity. Increased permeability monitored by changes in transendothelial electrical resistance and cytoskeletal remodelling caused by actin fiber rearrangement were observed when the cells were exposed to lupus serum and C5a, similar to the observations in mice. In addition, our data show that C5a/C5aR1 signalling alters nuclear factor-κB translocation into nucleus and regulates the expression of the tight junction proteins, claudin-5 and zonula occludens 1 in this setting. Our results demonstrate for the first time that C5a regulates BBB integrity in a neuroinflammatory setting where it affects both endothelial and astroglial cells. In addition, we also demonstrate that our previous findings in a mouse model, were emulated in human cells in vitro, bringing the studies one step closer to understanding the translational potential of C5a/C5aR1 blockade as a promising therapeutic strategy in SLE and other neurodegenerative diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.