Evidence map›Paper›PMID 31884386›Full record

ArticleMolecular immunology2020

Complement fragments are biomarkers of antibody-mediated endothelial injury.

Erik Stites, Brandon Renner, Jennifer Laskowski, Moglie Le Quintrec, Zhiying You, Brian Freed, James Cooper, Diana Jalal, Joshua M Thurman

Open access · greenAbstract read
In one paragraph

Article in Molecular immunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
0.7field-weighted citation impact, top 30% of its field
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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Noninvasive Diagnosis of Kidney Allograft Rejection.Journal of the American Society of Nephrology : JASN · 2025
    Review
  7. Circular RNAs: Regulators of endothelial cell dysfunction in atherosclerosis.Journal of molecular medicine (Berlin, Germany) · 2024
    Review
  8. The complement system in pediatric acute kidney injury.Pediatric nephrology (Berlin, Germany) · 2023
    Review
  9. Extracellular vesicles derived from patients with antibody-mediated rejection induce tubular senescence and endothelial to mesenchymal transition in renal cells.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2022
    Article
  10. COVID‑19 and ischemic stroke: Mechanisms of hypercoagulability (Review).International journal of molecular medicine · 2021
    Review
  11. Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction.International journal of molecular sciences · 2020
    Review
  12. Review
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 at 5 institutions in 3 countries.

Erik StitesDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Brandon RennerDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Jennifer LaskowskiDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Moglie Le QuintrecDepartment of Nephrology, Centre Hospitalier Universitaire de Montpellier, Montpellier, France.
Zhiying YouDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Brian FreedClinimmune Labs, Aurora, CO, USA.
James CooperDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
Diana JalalCarver College of Medicine, University of Iowa, Iowa City, IA, USA.
Joshua M ThurmanDepartment of Medicine, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: Joshua.Thurman@ucdenver.edu.
University of Colorado Anschutz Medical Campus · USUniversity of Colorado Denver · USBPS Bioscience (United States)Centre Hospitalier Universitaire de Montpellier · FRUniversity of Iowa · US

Funding

Colorado Clinical and Translational Sciences InstituteUL1TR001082 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2013 to 2017
$48.0M
The Complement System and Ischemic Acute Renal FailureR01DK076690 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Joshua M Thurman · 2008 to 2026
$6.6M
TRAINING IN RENAL &ELECTROLYTE DISEASE &HYPERTENSIONT32DK007135 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI JOHNSON, RICHARD JOSEPH, KENDRICK, JESSICA B · 1986 to 2024
$5.3M
Novel Therapeutic Approaches for Lupus NephritisR01DK125823 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI HOLERS, VERNON MICHAEL, THURMAN, JOSHUA M · 2020 to 2023
$1.8M
Immunologic Mechanisms of Progressive GlomerulosclerosisR01DK113586 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI THURMAN, JOSHUA M · 2017 to 2020
$1.4M
NCATS NIH HHS UL1 TR001082NIDDK NIH HHS R01 DK076690NIDDK NIH HHS R01 DK113586NIDDK NIH HHS R01 DK125823NIDDK NIH HHS T32 DK007135
6 · The paper itself

Abstract

Antibody-mediated rejection (AbMR) adversely affects long-term graft survival in kidney transplantation. Currently, the diagnosis of AbMR requires a kidney biopsy, and detection of complement C4d deposition in the allograft is one of the diagnostic criteria. Complement activation also generates several soluble fragments which could potentially provide non-invasive biomarkers of the process. Furthermore, microvesicles released into the plasma from injured cells can serve as biomarkers of vascular injury. To explore whether soluble complement fragments or complement fragments bound to endothelial microvesicles can be used to non-invasively detect AbMR, we developed an in vitro model in which human endothelial cells were exposed to anti-HLA antibodies and complement sufficient serum. We found that complement fragments C4a and sC5b-9 were increased in the supernatants of cells exposed to complement-sufficient serum compared to cells treated complement-deficient serum. Furthermore, complement activation on the cell surface was associated with the release of microvesicles bearing C4 and C3 fragments. We next measured these analytes in plasma from kidney transplant recipients with biopsy-proven acute AbMR (n = 9) and compared the results with those from transplant recipients who also had impaired allograft function but who did not have AbMR (n = 30). Consistent with the in vitro results, complement fragments C4a and Ba were increased in plasma from patients with AbMR compared to control subjects (P < 0.001 and P < 0.01, respectively). Endothelial microvesicle counts were not increased in patients with AbMR, however, and the number of microvesicles with C4 and C3 bound to the surface was actually lower compared to control subjects (both P < 0.05). Our results suggest that plasma complement activation fragments may be useful as non-invasive biomarkers of antibody-mediated complement activation within the allograft. Complement-opsonized endothelial microvesicles are decreased in patients with AbMR, possibly due to enhanced clearance of microvesicles opsonized with C3 and C4 fragments.

Indexed as

AdultAllograftsAntibodiesBiomarkersBiopsyCells, CulturedComplement ActivationComplement System ProteinsEndothelial CellsFemaleGraft RejectionHumansKidneyKidney TransplantationMaleMiddle AgedAntibodiesBiomarkersComplement System ProteinsAntibody mediated rejectionBiomarkerComplementDonor specific antibody

Identifiers

PMID31884386
PMCPMC7192552
OpenAlexW2997450876

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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.