Evidence map›Paper›PMID 30066197›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2018

Therapeutic potential of staphylococcal superantigen-like protein 7 for complement-mediated hemolysis.

Yan Li, Fiona Clow, John D Fraser, Feng Lin

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.4field-weighted citation impact, top 40% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

4 authors at 2 institutions in 2 countries.

Yan LiDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Fiona ClowDepartment of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
John D FraserDepartment of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand.
Feng LinDepartment of Inflammation and Immunity, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. Linf2@ccf.org.
Cleveland Clinic Lerner College of Medicine · USUniversity of Auckland · NZ

Funding

Nutrigenetic Intervention to Reduce Liver Fat in Hispanics - SupplementR01MD010358 · NIMHD · UNIVERSITY OF SOUTHERN CALIFORNIA · PI GORAN, MICHAEL ISAAC · 2016 to 2019
$3.3M
Complement and OsteoporosisR01AR061564 · NIAMS · CLEVELAND CLINIC LERNER COM-CWRU · PI DENNIS, JAMES E, LIN, FENG C · 2012 to 2015
$1.5M
Local inhibition of complement to improve MSC-based therapy for diabetesR01DK103581 · NIDDK · CLEVELAND CLINIC LERNER COM-CWRU · PI HAMILTON, THOMAS A., LIN, FENG C · 2015 to 2018
$1.4M
NIAMS NIH HHS R01 AR061564NIDDK NIH HHS DK10358NIDDK NIH HHS R01 DK103581NIMHD NIH HHS R01 MD010358
6 · The paper itself

Abstract

Previous studies have demonstrated that staphylococcal superantigen-like protein 7 (SSL7), a protein produced by Staphylococcus aureus, potently inhibits the formation of the complement membrane attack complex by binding to complement component 5 (C5). However, because of the predicted immunogenicity of SSL7 as a foreign protein in humans, its potential as a new complement inhibitor for treating complement-mediated diseases is uncertain. In this study, we found that administration of SSL7 significantly prevented complement-mediated hemolysis and reduced hemoglobinuria in a mouse model of complement-mediated intravascular hemolysis. Interestingly, although repetitive administrations of SSL7 elicited anti-SSL7 antibody production, administration of SSL7 at a dose of 2 μg/mouse was still able to significantly attenuate complement-mediated intravascular hemolysis in vivo in the presence of the antibodies. In addition, even though anti-SSL7 antibodies were detectable in normal human donors, these antibodies did not significantly reduce the complement inhibitory activity of SSL7 in in vitro assays. Finally, inoculation of SSL7 in the anterior chamber of the eye suppressed the production of SSL7-reactive antibodies after repetitive SSL7 administration. These results suggest that SSL7 could be developed as an economical alternative to the existing C5-targeted drug, eculizumab, especially for controlling acute complement activation in catastrophic conditions such as drug-induced immune hemolytic anemia and ABO-incompatible erythrocyte transfusions. These data also suggest that approaches such as anterior chamber-associated immune deviation could be employed to establish an antigen-specific immune tolerance for long-term SSL7 administration. KEY MESSAGES: • SSL7 functions in the presence of anti-SSL7 antibodies both in vitro and in vivo. • SSL7 has the potential to be developed as a new and economical complement inhibitor for treating complement-mediated hemolysis.

Indexed as

Anemia, HemolyticAnimalsAntibodies, BacterialBiomarkersComplement C5Disease Models, AnimalEnzyme-Linked Immunosorbent AssayExotoxinsHemolysisHumansMiceAntibodies, BacterialBiomarkersComplement C5Exotoxinsstaphylococcal exotoxin 1Complement inhibitionHemolysisSSL7

Identifiers

PMID30066197
PMCPMC6730541
OpenAlexW2887829470

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.