Evidence map›Paper›PMID 28159936›Full record

ArticleOncotarget2017

Nitration of tyrosines in complement factor H domains alters its immunological activity and mediates a pathogenic role in age related macular degeneration.

Matthew Krilis, Miao Qi, Michele C Madigan, Jason W H Wong, Mahmoud Abdelatti, Robyn H Guymer, John Whitelock, Peter McCluskey, Peng Zhang, Jian Qi and 3 more

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.3field-weighted citation impact, top 13% 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

7 citing papers in PubMed, 16 citations in OpenAlex.

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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

13 authors at 4 institutions in 2 countries.

Matthew KrilisSave Sight Institute, University of Sydney and Sydney Eye Hospital, Sydney, NSW, Australia.
Miao QiDepartment of Infectious Diseases, Immunology and Sexual Health and Department of Medicine, St George Hospital, University of New South Wales, Sydney, NSW, Australia.
Michele C MadiganSave Sight Institute, University of Sydney and Sydney Eye Hospital, Sydney, NSW, Australia.
Jason W H WongPrince of Wales Clinical School, University of New South Wales, Lowy Cancer Research Centre, Sydney, NSW, Australia.
Mahmoud AbdelattiDepartment of Infectious Diseases, Immunology and Sexual Health and Department of Medicine, St George Hospital, University of New South Wales, Sydney, NSW, Australia.
Robyn H GuymerCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Victoria, Australia.
John WhitelockGraduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, Australia.
Peter McCluskeySave Sight Institute, University of Sydney and Sydney Eye Hospital, Sydney, NSW, Australia.
Peng ZhangDepartment of Infectious Diseases, Immunology and Sexual Health and Department of Medicine, St George Hospital, University of New South Wales, Sydney, NSW, Australia.
Jian QiDepartment of Infectious Diseases, Immunology and Sexual Health and Department of Medicine, St George Hospital, University of New South Wales, Sydney, NSW, Australia.
Alex P HunyorSave Sight Institute, University of Sydney and Sydney Eye Hospital, Sydney, NSW, Australia.
Steven A KrilisDepartment of Infectious Diseases, Immunology and Sexual Health and Department of Medicine, St George Hospital, University of New South Wales, Sydney, NSW, Australia.
Bill GiannakopoulosDepartment of Infectious Diseases, Immunology and Sexual Health and Department of Medicine, St George Hospital, University of New South Wales, Sydney, NSW, Australia.
UNSW Sydney · AUUniversity of Sydney · AUSt George Hospital · AUCentre for Eye Research Australia · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nitrosative stress has been implicated in the pathogenesis of age related macular degeneration (AMD). Tyrosine nitration is a unique type of post translational modification that occurs in the setting of inflammation and nitrosative stress. To date, the significance and functional implications of tyrosine nitration of complement factor H (CFH), a key complement regulator in the eye has not been explored, and is examined in this study in the context of AMD pathogenesis.Sections of eyes from deceased individuals with AMD (n = 5) demonstrated the presence of immunoreactive nitrotyrosine CFH. We purified nitrated CFH from retinae from 2 AMD patients. Mass spectrometry of CFH isolated from AMD eyes revealed nitrated residues in domains critical for binding to heparan sulphate glycosaminoglycans (GAGs), lipid peroxidation by-products and complement (C) 3b.Functional studies revealed that nitrated CFH did not bind to lipid peroxidation products, nor to the GAG of perlecan nor to C3b. There was loss of cofactor activity for Factor I mediated cleavage of C3b with nitrated CFH compared to non-nitrated CFH. CFH inhibits, but nitrated CFH significantly potentiates, the secretion of the pro-inflammatory and angiogenic cytokine IL-8 from monocytes that have been stimulated with lipid peroxidation by-products. AMD patients (n = 30) and controls (n = 30) were used to measure plasma nitrated CFH using a novel ELISA. AMD patients had significantly elevated nitrated CFH levels compared to controls (p = 0.0117). These findings strongly suggest that nitrated CFH contributes to AMD progression, and is a target for therapeutic intervention.

Indexed as

Disease SusceptibilityImmunomodulationAgedAged, 80 and overAmino Acid SequenceBiomarkersCase-Control StudiesChoroidComplement C3bComplement Factor HEnzyme-Linked Immunosorbent AssayFemaleHeparan Sulfate ProteoglycansHumansMacular DegenerationMaleBiomarkersComplement C3bComplement Factor HHeparan Sulfate ProteoglycansPeptide FragmentsReactive Nitrogen SpeciesTyrosinecomplement factor Hmacular degenerationnitrosative stressretina

Identifiers

PMID28159936
PMCPMC5564745
OpenAlexW2584839030

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.