Evidence map›Paper›PMID 27773721›Full record

ArticleExperimental neurology2017

Identification of KRT16 as a target of an autoantibody response in complex regional pain syndrome.

Maral Tajerian, Victor Hung, Hamda Khan, Lauren J Lahey, Yuan Sun, Frank Birklein, Heidrun H Krämer, William H Robinson, Wade S Kingery, J David Clark

Open access · greenAbstract read
In one paragraph

Article in Experimental neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 5% 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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 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

10 authors at 3 institutions in 2 countries.

Maral TajerianVeterans Affairs Palo Alto Health Care System Palo Alto, CA, USA; Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, USA; Palo Alto Veterans Institute for Research, Palo Alto, CA, USA. Electronic address: maral@stanford.edu.
Victor HungVeterans Affairs Palo Alto Health Care System Palo Alto, CA, USA; Palo Alto Veterans Institute for Research, Palo Alto, CA, USA.
Hamda KhanVeterans Affairs Palo Alto Health Care System Palo Alto, CA, USA; Palo Alto Veterans Institute for Research, Palo Alto, CA, USA.
Lauren J LaheyVeterans Affairs Palo Alto Health Care System Palo Alto, CA, USA; Palo Alto Veterans Institute for Research, Palo Alto, CA, USA; Division of Immunology and Rheumatology, Stanford University, Stanford, CA, USA.
Yuan SunVeterans Affairs Palo Alto Health Care System Palo Alto, CA, USA; Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, USA; Palo Alto Veterans Institute for Research, Palo Alto, CA, USA.
Frank BirkleinDepartment of Neurology, University Medical Center, Mainz, Germany.
Heidrun H KrämerDepartment of Neurology, Justus Liebig University, Giessen, Germany.
William H RobinsonVeterans Affairs Palo Alto Health Care System Palo Alto, CA, USA; Palo Alto Veterans Institute for Research, Palo Alto, CA, USA; Division of Immunology and Rheumatology, Stanford University, Stanford, CA, USA.
Wade S KingeryVeterans Affairs Palo Alto Health Care System Palo Alto, CA, USA; Palo Alto Veterans Institute for Research, Palo Alto, CA, USA; Physical Medicine and Rehabilitation Service, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
J David ClarkVeterans Affairs Palo Alto Health Care System Palo Alto, CA, USA; Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, USA; Palo Alto Veterans Institute for Research, Palo Alto, CA, USA.
VA Palo Alto Health Care System · USJohannes Gutenberg University Mainz · DEJustus-Liebig-Universität Gießen · DE

Funding

Interdisciplinary Research Training in Pain and Substance Use DisordersT32DA035165 · NIDA · STANFORD UNIVERSITY · PI SEAN C MACKEY · 2013 to 2026
$7.2M
Mechanisms of Neuroinflammation after FractureR01NS072168 · NINDS · PALO ALTO VETERANS INSTIT FOR RESEARCH · PI KINGERY, WADE S · 2011 to 2014
$962k
NIDA NIH HHS T32 DA035165NINDS NIH HHS R01 NS072168
6 · The paper itself

Abstract

objectiveUsing a mouse model of complex regional pain syndrome (CRPS), our goal was to identify autoantigens in the skin of the affected limb.

methodsA CRPS-like state was induced using the tibia fracture/cast immobilization model. Three weeks after fracture, hindpaw skin was homogenized, run on 2-d gels, and probed by sera from fracture and control mice. Spots of interest were analyzed by liquid chromatography-mass spectroscopy (LC-MS) and the list of targets validated by examining their abundance and subcellular localization. In order to measure the autoantigenicity of selected protein targets, we quantified the binding of IgM in control and fracture mice sera, as well as in control and CRPS human sera, to the recombinant protein.

resultsWe show unique binding between fracture skin extracts and fracture sera, suggesting the presence of auto-antigens. LC-MS analysis provided us a list of potential targets, some of which were upregulated after fracture (KRT16, eEF1a1, and PRPH), while others showed subcellular-redistribution and increased membrane localization (ANXA2 and ENO3). No changes in protein citrullination or carbamylation were observed. In addition to increased abundance, KRT16 demonstrated autoantigenicity, since sera from both fracture mice and CRPS patients showed increased autoantibody binding to recombinant kRT16 protein.

conclusionsPursuing autoimmune contributions to CRPS provides a novel approach to understanding the condition and may allow the development of mechanism-based therapies. The identification of autoantibodies against KRT16 as a biomarker in mice and in humans is a critical step towards these goals, and towards redefining CRPS as having an autoimmune etiology.

Indexed as

AdultAnimalsAnnexin A2AutoantigensComplex Regional Pain SyndromesDisease Models, AnimalHindlimbHumansKeratin-6MaleMiceMice, Inbred C57BLMiddle AgedPeptide Elongation Factor 1PeripherinsPhosphopyruvate HydrataseAnnexin A2ANXA2 protein, humanAutoantigensEEF1A1 protein, humanKeratin-6KRT6A protein, humanPeptide Elongation Factor 1PeripherinsPhosphopyruvate HydratasePRPH protein, humanAnimal models of painAntigen identificationAutoimmunityChronic painComplex regional pain syndromeKeratin 16Skin

Identifiers

PMID27773721
PMCPMC5289288
OpenAlexW2536659826

What OpenQuestion holds

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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.