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  • Marklein, BiankaCharite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Charite Campus Mitte, Rheumatol Forschungslab AG Skriner, Charitepl 1,Intern Virchowweg 11,5-OG,R011, D-10117 Berlin, Germany (author)

The citrullinated/native index of autoantibodies against hnRNP-DL predicts an individual "window of treatment success" in RA patients

  • Article/chapterEnglish2021

Publisher, publication year, extent ...

  • 2021-09-14
  • BioMed Central (BMC),2021
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-456854
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-456854URI
  • https://doi.org/10.1186/s13075-021-02603-xDOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:147585996URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Correction in: Arthritis Research & Therapy, Volume 23, Issue 1, Article Number 255, DOI 10.1186/s13075-021-02639-z
  • BackgroundThere is a need for biomarker to identify patients “at risk” for rheumatoid arthritis (risk-RA) and to better predict the therapeutic response and in this study we tested the hypothesis that novel native and citrullinated heterogeneous nuclear ribonucleoprotein (hnRNP)-DL autoantibodies could be possible biomarkers.MethodsUsing protein macroarray and ELISA, epitope recognition against hnRNP-DL was analysed in sera from different developed RA disease and diagnosed SLE patients. Toll-like receptor (TLR) 7/9 and myeloid differentiation primary response gene 88 (MyD88)-dependency were studied in sera from murine disease models. HnRNP-DL expression in cultivated cells and synovial tissue was analysed by indirect immunofluorescence, immunoblot and immunohistochemistry.ResultsHnRNP-DL was highly expressed in stress granules, citrullinated in the rheumatoid joint and targeted by autoantibodies either as native or citrullinated proteins in patient subsets with different developed RA disease. Structural citrullination dependent epitopes (SCEs) of hnRNP-DL were detected in 58% of the SLE patients although 98% of these sera were α-CCP-2-negative. To obtain a specific citrullinated signal value, we subtracted the native antibody value from the citrullinated signal. The citrullinated/native index of autoantibodies against hnRNP-DL (CNDL-Index) was identified as a new value for an “individual window of treatment success” in early RA and for the detection of RF IgM/α-CCP-2 seronegative RA patients (24–46%). Negative CNDL-index was found in SLE patients, risk-RA and early RA cohorts such as EIRA where the majority of these patients are DAS28-responders to methotrexate (MTX) treatment (87%). High positive CNDL-values were associated with more severe RA, shared epitope and parenchymal changes in the lung. Specifically, native α-hnRNP-DL is TLR7/9-dependent, associated with pain and ROC analysis revealed an association to initial MTX or etanercept treatment response, especially in seronegative RA patients.ConclusionCNDL-index defines people at risk to develop RA and the “window of treatment success” thereby closing the sensitivity gap in RA.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Jenning, MadeleineCharite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Charite Campus Mitte, Rheumatol Forschungslab AG Skriner, Charitepl 1, Intern Virchowweg 11, 5-OG, R011, D-10117 Berlin, Germany; Leibniz Inst, German Rheumatism Res Ctr, D-10117 Berlin, Germany (author)
  • Konthur, ZoltánMax Planck Inst Mol Genet, Berlin, Germany; Max Planck Inst Colloids & Interfaces, Potsdam, Germany; Bundesanstalt Mat Forsch & Prufung BAM, Dept Analyt Chem, Dept 1, Berlin, Germany (author)
  • Häupl, ThomasCharite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Charite Campus Mitte, Rheumatol Forschungslab AG Skriner, Charitepl 1,Intern Virchowweg 11,5-OG,R011, D-10117 Berlin, Germany (author)
  • Welzel, FranziskaMax Planck Inst Mol Genet, Berlin, Germany (author)
  • Nonhoff, UteMax Planck Inst Mol Genet, Berlin, Germany (author)
  • Krobitsch, SylviaMax Planck Inst Mol Genet, Berlin, Germany (author)
  • Mulder, Debbie M.Radboud Univ Nijmegen, Dept Expt Rheumatol, Med Ctr, Nijmegen, Netherlands (author)
  • Koenders, Marije I.Radboud Univ Nijmegen, Dept Expt Rheumatol, Med Ctr, Nijmegen, Netherlands (author)
  • Joshua, VijayKarolinska Institutet (author)
  • Cope, Andrew P.Kings Coll London, Fac Life Sci & Med, Ctr Rheumat Dis, Sch Immunol & Microbial Sci, London, England (author)
  • Shlomchik, Mark J.Univ Pittsburgh, Dept Immunol, Sch Med, Pittsburgh, PA USA (author)
  • Anders, Hans-JoachimLudwig Maximilian Univ Hosp, Nephrol Ctr, Med Clin & Policlin 4, Munich, Germany (author)
  • Burmester, Gerd R.Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Charite Campus Mitte, Rheumatol Forschungslab AG Skriner, Charitepl 1,Intern Virchowweg 11,5-OG,R011, D-10117 Berlin, Germany (author)
  • Hensvold, AaseKarolinska Institutet (author)
  • Catrina, Anca I.Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Div Rheumatol, Stockholm, Sweden (author)
  • Rönnelid, JohanUppsala universitet,Klinisk immunologi(Swepub:uu)joharonn (author)
  • Steiner, GünterMed Univ Vienna, Div Rheumatol, Vienna, Austria; Ludwig Boltzmann Cluster Arthrit & Rehabil, Vienna, Austria (author)
  • Skriner, KarlCharite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Charite Campus Mitte, Rheumatol Forschungslab AG Skriner, Charitepl 1, Intern Virchowweg 11, 5-OG, R011, D-10117 Berlin, Germany; Leibniz Inst, German Rheumatism Res Ctr, D-10117 Berlin, Germany (author)
  • Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Charite Campus Mitte, Rheumatol Forschungslab AG Skriner, Charitepl 1,Intern Virchowweg 11,5-OG,R011, D-10117 Berlin, GermanyCharite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Charite Campus Mitte, Rheumatol Forschungslab AG Skriner, Charitepl 1, Intern Virchowweg 11, 5-OG, R011, D-10117 Berlin, Germany; Leibniz Inst, German Rheumatism Res Ctr, D-10117 Berlin, Germany (creator_code:org_t)

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  • In:Arthritis Research & Therapy: BioMed Central (BMC)23:11478-6362

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