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Sökning: onr:"swepub:oai:prod.swepub.kib.ki.se:144601001" > Bacterial citrullin...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003622naa a2200397 4500
001oai:prod.swepub.kib.ki.se:144601001
003SwePub
008240902s2020 | |||||||||||000 ||eng|
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1446010012 URI
0247 a https://doi.org/10.1136/annrheumdis-2019-2169192 DOI
040 a (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Jenning, M4 aut
2451 0a Bacterial citrullinated epitopes generated by Porphyromonas gingivalis infection-a missing link for ACPA production
264 c 2020-06-12
264 1b BMJ,c 2020
520 a Porphyromonas gingivalis (P.g.) is discussed to be involved in triggering self-reactive immune responses. The aim of this study was to investigate the autocitrullinated prokaryotic peptidylarginine deiminase (PPAD) from P.g. CH2007 (RACH2007-PPAD) from a rheumatoid arthritis (RA) patient and a synthetic citrullinated PPAD peptide (CPP) containing the main autocitrullination site as potential targets for antibody reactivity in RA and to analyse the possibility of citrullinating native human proteins by PPAD in the context of RA.MethodsRecombinant RACH2007-PPAD was cloned and expressed in Escherichia coli. Purified RACH2007-PPAD and its enzymatic activity was analysed using two-dimensional electrophoresis, mass spectrometry, immunoblot and ELISA. Autoantibody response to different modified proteins and peptides was recorded and bioinformatically evaluated.ResultsRACH2007-PPAD was capable to citrullinate major RA autoantigens, such as fibrinogen, vimentin, hnRNP-A2/B1, histone H1 and multiple peptides, which identify a common RG/RGG consensus motif. 33% of RA patients (n=30) revealed increased reactivity for α-cit-RACH2007-PPAD before RA onset. 77% of RA patients (n=99) presented α-cit-specific signals to CPP amino acids 57–71 which were positively correlated to α-CCP2 antibody levels. Interestingly, 48% of the α-CPP-positives were rheumatoidfactor IgM/anti-citrullinated peptide/protein antibodies (ACPA)-negative. Anti-CPP and α-RACH2007-PPAD antibody levels increase with age. Protein macroarrays that were citrullinated by RACH2007-PPAD and screened with RA patient sera (n=6) and controls (n=4) uncovered 16 RACH2007-PPAD citrullinated RA autoantigens and 9 autoantigens associated with lung diseases. We showed that the α-CPP response could be an important determinant in parenchymal changes in the lung at the time of RA diagnosis (n=106; p=0.018).ConclusionsRACH2007-PPAD induced internal citrullination of major RA autoantigens. Anti-RACH2007-PPAD correlates with ACPA levels and interstitial lung disease autoantigen reactivity, supporting an infection-based concept for induction of ACPAs via enzymatic mimicry.
7001 a Marklein, B4 aut
7001 a Ytterberg, J4 aut
7001 a Zubarev, RAu Karolinska Institutet4 aut
7001 a Joshua, Vu Karolinska Institutet4 aut
7001 a van Schaardenburg, D4 aut
7001 a van de Stadt, L4 aut
7001 a Catrina, AIu Karolinska Institutet4 aut
7001 a Nonhoff, U4 aut
7001 a Haupl, T4 aut
7001 a Konthur, Z4 aut
7001 a Burmester, GR4 aut
7001 a Skriner, K4 aut
7102 a Karolinska Institutet4 org
7730 t Annals of the rheumatic diseasesd : BMJg 79:9, s. 1194-1202q 79:9<1194-1202x 1468-2060x 0003-4967
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:144601001
8564 8u https://doi.org/10.1136/annrheumdis-2019-216919

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