Evidence map›Paper›PMID 39212707›Full record

ArticleCellular and molecular life sciences : CMLS2024

Submicron immunoglobulin particles exhibit FcγRII-dependent toxicity linked to autophagy in TNFα-stimulated endothelial cells.

Wanida C Hollis, Sehrish Farooq, M Reza Khoshi, Mehulkumar Patel, Elena Karnaukhova, Nancy Eller, Karel Holada, Dorothy E Scott, Jan Simak

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Wanida C HollisCenter for Biologics Evaluation and Research, FDA, Silver Spring, MD, USA.
Sehrish FarooqCenter for Biologics Evaluation and Research, FDA, Silver Spring, MD, USA.
M Reza KhoshiCenter for Biologics Evaluation and Research, FDA, Silver Spring, MD, USA.
Mehulkumar PatelCenter for Biologics Evaluation and Research, FDA, Silver Spring, MD, USA.
Elena KarnaukhovaCenter for Biologics Evaluation and Research, FDA, Silver Spring, MD, USA.
Nancy EllerCenter for Biologics Evaluation and Research, FDA, Silver Spring, MD, USA.
Karel HoladaInstitute of Immunology and Microbiology, First Faculty of Medicine, Charles University, Prague, Czech Republic.
Dorothy E ScottCenter for Biologics Evaluation and Research, FDA, Silver Spring, MD, USA.
Jan SimakCenter for Biologics Evaluation and Research, FDA, Silver Spring, MD, USA. jan.simak@fda.hhs.gov.ORCID http://orcid.org/0000-0001-8910-7362

Funding

U.S. Food and Drug Administration U.S. Food and Drug Administration
6 · The paper itself

Abstract

In intravenous immunoglobulins (IVIG), and some other immunoglobulin products, protein particles have been implicated in adverse events. Role and mechanisms of immunoglobulin particles in vascular adverse effects of blood components and manufactured biologics have not been elucidated. We have developed a model of spherical silica microparticles (SiMPs) of distinct sizes 200-2000 nm coated with different IVIG- or albumin (HSA)-coronas and investigated their effects on cultured human umbilical vein endothelial cells (HUVEC). IVIG products (1-20 mg/mL), bare SiMPs or SiMPs with IVIG-corona, did not display significant toxicity to unstimulated HUVEC. In contrast, in TNFα-stimulated HUVEC, IVIG-SiMPs induced decrease of HUVEC viability compared to HSA-SiMPs, while no toxicity of soluble IVIG was observed. 200 nm IVIG-SiMPs after 24 h treatment further increased ICAM1 (intercellular adhesion molecule 1) and tissue factor surface expression, apoptosis, mammalian target of rapamacin (mTOR)-dependent activation of autophagy, and release of extracellular vesicles, positive for mitophagy markers. Toxic effects of IVIG-SiMPs were most prominent for 200 nm SiMPs and decreased with larger SiMP size. Using blocking antibodies, toxicity of IVIG-SiMPs was found dependent on FcγRII receptor expression on HUVEC, which increased after TNFα-stimulation. Similar results were observed with different IVIG products and research grade IgG preparations. In conclusion, submicron particles with immunoglobulin corona induced size-dependent toxicity in TNFα-stimulated HUVEC via FcγRII receptors, associated with apoptosis and mTOR-dependent activation of autophagy. Testing of IVIG toxicity in endothelial cells prestimulated with proinflammatory cytokines is relevant to clinical conditions. Our results warrant further studies on endothelial toxicity of sub-visible immunoglobulin particles.

Indexed as

AutophagyHuman Umbilical Vein Endothelial CellsImmunoglobulins, IntravenousReceptors, IgGTumor Necrosis Factor-alphaApoptosisCell SurvivalHumansIntercellular Adhesion Molecule-1Particle SizeProtein CoronaSilicon DioxideTOR Serine-Threonine KinasesImmunoglobulins, IntravenousIntercellular Adhesion Molecule-1Protein CoronaReceptors, IgGSilicon DioxideTOR Serine-Threonine KinasesTumor Necrosis Factor-alphaBiologicsContaminantsFcγRImmunogenicityMembrane microparticlesProtein aggregatesProtein coronaVascular toxicityVessel wall

Identifiers

PMID39212707
PMCPMC11364738

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Registered trials

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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.