Evidence map›Paper›PMID 22198950›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2012

Pathogenic natural antibodies propagate cerebral injury following ischemic stroke in mice.

Andrew Elvington, Carl Atkinson, Liudmila Kulik, Hong Zhu, Jin Yu, Mark S Kindy, V Michael Holers, Stephen Tomlinson

Abstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
51citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 20% 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

51 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.

  1. Pooled it
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  12. Increasing the efficacy and safety of a human complement inhibitor for treating post-transplant cardiac ischemia reperfusion injury by targeting to a graft-specific neoepitope.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2021
    Article
  13. Article
  14. Review
  15. Pathophysiologic mechanisms of cerebral endotheliopathy and stroke due to Sars-CoV-2.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021
    Review
  16. Article
  17. A novel injury site-natural antibody targeted complement inhibitor protects against lung transplant injury.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021
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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

8 authors at 2 institutions in 1 country.

Andrew ElvingtonDepartment of Microbiology and Immunology, Children's Research Institute, Medical University of South Carolina, Charleston, SC 29401, USA.
Carl Atkinson
Liudmila Kulik
Hong Zhu
Jin Yu
Mark S Kindy
V Michael Holers
Stephen Tomlinson
Medical University of South Carolina · USUniversity of Colorado Denver · US

Funding

MOUSE MEMBRANE RCA PROTEINS IN THE IMMUNE RESPONSER01AI031105 · NIAID · UNIVERSITY OF COLORADO DENVER · PI HOLERS, VERNON MICHAEL · 1993 to 2008
$2.6M
Controlling complement in cerebral ischemic injuryR01HL082485 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI TOMLINSON, STEPHEN · 2006 to 2010
$1.6M
Role of complement in brain death induced injury to donor heartsR01HL086576 · NHLBI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI TOMLINSON, STEPHEN · 2007 to 2010
$1.5M
Complement, anti-tumor immunity and apoptosis-based therapyR01CA158179 · NCI · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI TOMLINSON, STEPHEN · 2012 to 2016
$1.5M
NCI NIH HHS R01 CA158179NHLBI NIH HHS HL082485NHLBI NIH HHS HL86576NHLBI NIH HHS R01 HL082485NHLBI NIH HHS R01 HL086576NIAID NIH HHS AI31105NIAID NIH HHS R01 AI031105
6 · The paper itself

Abstract

Self-reactive natural Abs initiate injury following ischemia and reperfusion of certain tissues, but their role in ischemic stroke is unknown. We investigated neoepitope expression in the postischemic brain and the role of natural Abs in recognizing these epitopes and mediating complement-dependent injury. A novel IgM mAb recognizing a subset of phospholipids (C2) and a previously characterized anti-annexin IV mAb (B4) were used to reconstitute and characterize injury in Ab-deficient Rag1(-/-) mice after 60 min of middle cerebral artery occlusion and reperfusion. Reconstitution with C2 or B4 mAb in otherwise protected Rag1(-/-) mice restored injury to that seen in wild-type (wt) mice, as demonstrated by infarct volume, demyelination, and neurologic scoring. IgM deposition was demonstrated in both wt mice and reconstituted Rag1(-/-) mice, and IgM colocalized with the complement activation fragment C3d following B4 mAb reconstitution. Further, recombinant annexin IV significantly reduced infarct volumes in wt mice and in Rag1(-/-) mice administered normal mouse serum, demonstrating that a single Ab reactivity is sufficient to develop cerebral ischemia reperfusion injury in the context of an entire natural Ab repertoire. Finally, C2 and B4 mAbs bound to hypoxic, but not normoxic, human endothelial cells in vitro. Thus, the binding of pathogenic natural IgM to postischemic neoepitopes initiates complement-dependent injury following murine cerebral ischemia and reperfusion, and, based also on previous data investigating IgM reactivity in human serum, there appears to be a similar recognition system in both mouse and man.

Indexed as

AutoantibodiesAnimalsAntibodies, MonoclonalBrain IschemiaComplement ActivationComplement C3Immunoglobulin MMiceReperfusion InjuryStrokeAntibodies, MonoclonalAutoantibodiesComplement C3Immunoglobulin M

Identifiers

PMID22198950
PMCPMC3262954
OpenAlexW2152202709

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.