Trial reportThe Journal of biological chemistry2012
Heavy chains of inter alpha inhibitor (IαI) inhibit the human complement system at early stages of the cascade.
Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 43 citations in OpenAlex.
- [Serum inter-alpha-trypsin inhibitor heavy chain H3 is identified as a potential biomarker for myopenia in patients with rheumatoid arthritis using proteomic profiling].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2025Article
- Inter-alpha-trypsin inhibitor heavy chain H3 is a potential biomarker for disease activity in myasthenia gravis.Acta neuropathologica · 2024Article
- Urine inter-alpha-trypsin inhibitor family-related proteins may serve as biomarkers for disease activity of lupus.Journal of clinical laboratory analysis · 2022Article
- Defining the versican interactome in lung health and disease.American journal of physiology. Cell physiology · 2022Review
- Modulation of hyaluronan signaling as a therapeutic target in human disease.Pharmacology & therapeutics · 2022Review
- Citrullinated inter-alpha-trypsin inhibitor heavy chain 4 in arthritic joints and its potential effect in the neutrophil migration.Clinical and experimental immunology · 2021Article
- ITIH4 acts as a protease inhibitor by a novel inhibitory mechanism.Science advances · 2021Article
- Novel Neuroprotective Agents to Treat Neonatal Hypoxic-Ischemic Encephalopathy: Inter-Alpha Inhibitor Proteins.International journal of molecular sciences · 2020Review
- The Inter-α-Trypsin Inhibitor Family: Versatile Molecules in Biology and Pathology.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2020Review
- Ontogeny of inter-alpha inhibitor protein (IAIP) expression in human brain.Journal of neuroscience research · 2020Article
- Inter-α-inhibitor heavy chain-1 has an integrin-like 3D structure mediating immune regulatory activities and matrix stabilization during ovulation.The Journal of biological chemistry · 2020Article
- Matrix-degrading protease ADAMTS-5 cleaves inter-α-inhibitor and releases active heavy chain 2 in synovial fluids from arthritic patients.The Journal of biological chemistry · 2019Article
- Hyaluronan interactions with innate immunity in lung biology.Matrix biology : journal of the International Society for Matrix Biology · 2019Review
- Intravascular heavy chain-modification of hyaluronan during endotoxic shock.Biochemistry and biophysics reports · 2019Article
- Inter-α-inhibitor deficiency in the mouse is associated with alterations in anxiety-like behavior, exploration and social approach.Genes, brain, and behavior · 2019Article
- Identification of novel biomarker as citrullinated inter-alpha-trypsin inhibitor heavy chain 4, specifically increased in sera with experimental and rheumatoid arthritis.Arthritis research & therapy · 2018Article
- Alterations in inter-alpha inhibitor protein expression after hypoxic-ischemic brain injury in neonatal rats.International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience · 2018Article
- Article
- Analysis of complement biomarkers in systemic sclerosis indicates a distinct pattern in scleroderma renal crisis.Arthritis research & therapy · 2016Article
- Human serum-derived protein removes the need for coating in defined human pluripotent stem cell culture.Nature communications · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inter alpha inhibitor (IαI) is an abundant serum protein consisting of three polypeptides: two heavy chains (HC1 and HC2) and bikunin, a broad-specificity Kunitz-type proteinase inhibitor. The complex is covalently held together by chondroitin sulfate but during inflammation IαI may interact with TNF-stimulated gene 6 protein (TSG-6), which supports transesterification of heavy chains to hyaluronan. Recently, IαI was shown to inhibit mouse complement in vivo and to protect from complement-mediated lung injury but the mechanism of such activity was not elucidated. Using human serum depleted from IαI, we found that IαI is not an essential human complement inhibitor as was reported for mice and that such serum has unaltered hemolytic activity. However, purified human IαI inhibited classical, lectin and alternative complement pathways in vitro when added in excess to human serum. The inhibitory activity was dependent on heavy chains but not bikunin and detected at the level of initiating molecules (MBL, properdin) in the lectin/alternative pathways or C4b in the classical pathway. Furthermore, IαI affected formation and assembly of the C1 complex and prevented assembly of the classical pathway C3-convertase. Presence and putative interactions with TSG-6 did not affect the ability of IαI to inhibit complement thus implicating IαI as a potentially important complement inhibitor once enriched onto hyaluronan moieties in the course of local inflammatory processes. In support of this, we found a correlation between IαI/HC-containing proteins and hemolytic activity of synovial fluid from patients suffering from rheumatoid arthritis.
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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.