Evidence map›Paper›PMID 26333287›Full record

ArticleAutoimmunity2015

Mapping epitopes of U1-70K autoantibodies at single-amino acid resolution.

David James Haddon, Justin Ansel Jarrell, Vivian K Diep, Hannah E Wand, Jordan V Price, Stephanie Tangsombatvisit, Grace M Credo, Sally Mackey, Cornelia L Dekker, Emily C Baechler and 3 more

Registry-linked trialOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Autoimmunity, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01827462 (Immune Senescence in the Elderly), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.4field-weighted citation impact, top 12% 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.

NCT01827462 phase4completednot on this map

Immune Senescence in the Elderly: Comparison of Immune Responses to Influenza Vaccine In Adults of Different Ages

TypeinterventionalSponsorStanford UniversityRan2007 to 2017Enrolled136ConditionsInfluenzaArmsTrivalent, inactivated influenza vaccine (TIV), Quadrivalent, inactivated influenza vaccine (IIV4), High-Dose Trivalent, inactivated influenza vaccine (TIV High-Dose)
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 13 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 1 country.

David James Haddona Department of Medicine , Division of Immunology & Rheumatology, Stanford University School of Medicine , Stanford , CA , USA .
Justin Ansel Jarrella Department of Medicine , Division of Immunology & Rheumatology, Stanford University School of Medicine , Stanford , CA , USA .
Vivian K Diepa Department of Medicine , Division of Immunology & Rheumatology, Stanford University School of Medicine , Stanford , CA , USA .
Hannah E Wanda Department of Medicine , Division of Immunology & Rheumatology, Stanford University School of Medicine , Stanford , CA , USA .
Jordan V Priceb Department of Molecular and Cell Biology, Division of Immunology and Pathogenesis , University of California at Berkeley , Berkeley , CA , USA .
Stephanie Tangsombatvisita Department of Medicine , Division of Immunology & Rheumatology, Stanford University School of Medicine , Stanford , CA , USA .
Grace M Credoc Intel Corporation , Santa Clara , CA , USA .
Sally Mackeyd Department of Pediatrics, Division of Infectious Diseases , Stanford University School of Medicine , Stanford , CA , USA , and.
Cornelia L Dekkerd Department of Pediatrics, Division of Infectious Diseases , Stanford University School of Medicine , Stanford , CA , USA , and.
Emily C Baechlere Department of Medicine , Division of Rheumatic and Autoimmune Diseases, University of Minnesota Medical School , Minneapolis , MN , USA.
Chih Long Liua Department of Medicine , Division of Immunology & Rheumatology, Stanford University School of Medicine , Stanford , CA , USA .
Madoo Varmac Intel Corporation , Santa Clara , CA , USA .
Paul J Utza Department of Medicine , Division of Immunology & Rheumatology, Stanford University School of Medicine , Stanford , CA , USA .
Stanford Medicine · USIntel (United States) · USUniversity of California, Berkeley · USUniversity of Minnesota Medical Center · US

Funding

Supplement - Inflammatory Triggers in B Cell AutoimmunityU19AI056363 · NIAID · DUKE UNIVERSITY · PI ST. CLAIR, EUGENE WILLIAM · 2003 to 2017
$35.3M
Virginia Mason/UCHSC Autoimmune Prevention CenterU19AI050864 · NIAID · UNIVERSITY OF COLORADO DENVER · PI EISENBARTH, GEORGE S · 2001 to 2011
$29.2M
Stanford Center for Clinical and Translational Education and Research (SCCTER)UL1UL1RR025744 · NCRR · STANFORD UNIVERSITY · PI GREENBERG, HARRY BERNARD · 2008 to 2011
$22.4M
Vaccination and infection: indicators of immunological health and responsivenessU19AI090019 · NIAID · STANFORD UNIVERSITY · PI GREENBERG, HARRY BERNARD · 2010 to 2015
$17.3M
Th17 lymphocytes in human autoimmune diseasesU19AI082719 · NIAID · STANFORD UNIVERSITY · PI FATHMAN, CHARLES GARRISON · 2009 to 2013
$3.4M
Profiling Epigenetic Biomarkers for the Study and Treatment of LupusF32AI080086 · NIAID · STANFORD UNIVERSITY · PI LIU, CHIH LONG · 2009 to 2010
$108k
Canadian Institutes of Health Research 2 OR-92141NCRR NIH HHS UL1 RR025744NIAID NIH HHS 1 U19 AI090019NIAID NIH HHS 5 F32AI-080086-02NIAID NIH HHS 5 U19-AI050864NIAID NIH HHS 5 U19-AI056363NIAID NIH HHS 5 U19-AI082719NIAID NIH HHS F32 AI080086NIAID NIH HHS U19 AI050864NIAID NIH HHS U19 AI056363NIAID NIH HHS U19 AI082719NIAID NIH HHS U19 AI090019NIAID NIH HHS U19AI090019PHS HHS HSN288201000034C
6 · The paper itself

Abstract

The mechanisms underlying development of ribonucleoprotein (RNP) autoantibodies are unclear. The U1-70K protein is the predominant target of RNP autoantibodies, and the RNA binding domain has been shown to be the immunodominant autoantigenic region of U1-70K, although the specific epitopes are not known. To precisely map U1-70K epitopes, we developed silicon-based peptide microarrays with >5700 features, corresponding to 843 unique peptides derived from the U1-70K protein. The microarrays feature overlapping peptides, with single-amino acid resolution in length and location, spanning amino acids 110-170 within the U1-70K RNA binding domain. We evaluated the serum IgG of a cohort of patients with systemic lupus erythematosus (SLE; n = 26) using the microarrays, and identified multiple reactive epitopes, including peptides 116-121 and 143-148. Indirect peptide ELISA analysis of the sera of patients with SLE (n = 88) revealed that ∼14% of patients had serum IgG reactivity to 116-121, while reactivity to 143-148 appeared to be limited to a single patient. SLE patients with serum reactivity to 116-121 had significantly lower SLE Disease Activity Index (SLEDAI) scores at the time of sampling, compared to non-reactive patients. Minimal reactivity to the peptides was observed in the sera of healthy controls (n = 92). Competitive ELISA showed antibodies to 116-121 bind a common epitope in U1-70K (68-72) and the matrix protein M1 of human influenza B viruses. Institutional Review Boards approved this study. Knowledge of the precise epitopes of U1-70K autoantibodies may provide insight into the mechanisms of development of anti-RNP, identify potential clinical biomarkers and inform ongoing clinical trails of peptide-based therapeutics.

Indexed as

Amino AcidsAmino Acid SequenceAutoantibodiesAutoantigensCase-Control StudiesEpitope MappingEpitopesGene ExpressionHumansImmunoglobulin GLupus Erythematosus, SystemicMolecular Sequence DataPeptide MappingProtein Array AnalysisProtein BindingProtein Structure, TertiaryAmino AcidsAutoantibodiesAutoantigensEpitopesImmunoglobulin GM1 matrix protein, influenza B virusRibonucleoprotein, U1 Small NuclearSNRNP70 protein, humanViral Matrix ProteinsribonucleoproteinRNPSilicon-based peptide microarraySLEsystemic lupus erythematosus

Identifiers

PMID26333287
PMCPMC4815922
OpenAlexW1923559986

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Registered trials

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.