Expanding the citrullinome of synovial fibrinogen from rheumatoid arthritis patients

Mandvi Sharma, Dres Damgaard, Ladislav Senolt, Birte Svensson, Anne Christine Bay-Jensen, Claus Henrik Nielsen, Per Hägglund

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Citrullination is a post-translational protein modification, which is associated with inflammation in general and is thought to play an important pathogenic role in rheumatoid arthritis (RA). Here a mass spectrometry-based proteomics approach was applied to identify citrullination sites in synovial fluid fibrinogen from four RA patients. In general, high disease activity correlated with increased number of identified citrullination sites and higher relative citrulline occupancy. Altogether, 23 sites were identified, of which 9 have not been previously reported to be citrullinated in vivo. Citrullination at site α84, α123, α129, α547, α573, α591, β334 and γ134 was identified in more than one patient, and these positions were therefore regarded as hotspots. Following citrullination of fibrinogen in vitro using human recombinant peptidylarginine deiminase 2 (PAD2), a total of 46 citrullination sites were identified, including 6 hitherto unreported in vitro citrullination sites. Twenty-two out of the 23 citrullination sites identified in vivo were also detected in vitro, supporting the validity of the identifications. Significance: This work provides information about previously uncharacterized citrullination sites in synovial fluid fibrinogen from rheumatoid arthritis patients. Detection of these novel citrullination sites may prove to have diagnostic or prognostic value in RA and enhance our understanding of the immune pathogenesis.
Original languageEnglish
Article number103484
JournalJournal of Proteomics
Volume208
Number of pages7
ISSN1874-3919
DOIs
Publication statusPublished - 2019

Cite this

Sharma, M., Damgaard, D., Senolt, L., Svensson, B., Bay-Jensen, A. C., Nielsen, C. H., & Hägglund, P. (2019). Expanding the citrullinome of synovial fibrinogen from rheumatoid arthritis patients. Journal of Proteomics, 208, [103484]. https://doi.org/10.1016/j.jprot.2019.103484
Sharma, Mandvi ; Damgaard, Dres ; Senolt, Ladislav ; Svensson, Birte ; Bay-Jensen, Anne Christine ; Nielsen, Claus Henrik ; Hägglund, Per. / Expanding the citrullinome of synovial fibrinogen from rheumatoid arthritis patients. In: Journal of Proteomics. 2019 ; Vol. 208.
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abstract = "Citrullination is a post-translational protein modification, which is associated with inflammation in general and is thought to play an important pathogenic role in rheumatoid arthritis (RA). Here a mass spectrometry-based proteomics approach was applied to identify citrullination sites in synovial fluid fibrinogen from four RA patients. In general, high disease activity correlated with increased number of identified citrullination sites and higher relative citrulline occupancy. Altogether, 23 sites were identified, of which 9 have not been previously reported to be citrullinated in vivo. Citrullination at site α84, α123, α129, α547, α573, α591, β334 and γ134 was identified in more than one patient, and these positions were therefore regarded as hotspots. Following citrullination of fibrinogen in vitro using human recombinant peptidylarginine deiminase 2 (PAD2), a total of 46 citrullination sites were identified, including 6 hitherto unreported in vitro citrullination sites. Twenty-two out of the 23 citrullination sites identified in vivo were also detected in vitro, supporting the validity of the identifications. Significance: This work provides information about previously uncharacterized citrullination sites in synovial fluid fibrinogen from rheumatoid arthritis patients. Detection of these novel citrullination sites may prove to have diagnostic or prognostic value in RA and enhance our understanding of the immune pathogenesis.",
author = "Mandvi Sharma and Dres Damgaard and Ladislav Senolt and Birte Svensson and Bay-Jensen, {Anne Christine} and Nielsen, {Claus Henrik} and Per H{\"a}gglund",
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Sharma, M, Damgaard, D, Senolt, L, Svensson, B, Bay-Jensen, AC, Nielsen, CH & Hägglund, P 2019, 'Expanding the citrullinome of synovial fibrinogen from rheumatoid arthritis patients', Journal of Proteomics, vol. 208, 103484. https://doi.org/10.1016/j.jprot.2019.103484

Expanding the citrullinome of synovial fibrinogen from rheumatoid arthritis patients. / Sharma, Mandvi; Damgaard, Dres; Senolt, Ladislav; Svensson, Birte; Bay-Jensen, Anne Christine; Nielsen, Claus Henrik; Hägglund, Per.

In: Journal of Proteomics, Vol. 208, 103484, 2019.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Expanding the citrullinome of synovial fibrinogen from rheumatoid arthritis patients

AU - Sharma, Mandvi

AU - Damgaard, Dres

AU - Senolt, Ladislav

AU - Svensson, Birte

AU - Bay-Jensen, Anne Christine

AU - Nielsen, Claus Henrik

AU - Hägglund, Per

PY - 2019

Y1 - 2019

N2 - Citrullination is a post-translational protein modification, which is associated with inflammation in general and is thought to play an important pathogenic role in rheumatoid arthritis (RA). Here a mass spectrometry-based proteomics approach was applied to identify citrullination sites in synovial fluid fibrinogen from four RA patients. In general, high disease activity correlated with increased number of identified citrullination sites and higher relative citrulline occupancy. Altogether, 23 sites were identified, of which 9 have not been previously reported to be citrullinated in vivo. Citrullination at site α84, α123, α129, α547, α573, α591, β334 and γ134 was identified in more than one patient, and these positions were therefore regarded as hotspots. Following citrullination of fibrinogen in vitro using human recombinant peptidylarginine deiminase 2 (PAD2), a total of 46 citrullination sites were identified, including 6 hitherto unreported in vitro citrullination sites. Twenty-two out of the 23 citrullination sites identified in vivo were also detected in vitro, supporting the validity of the identifications. Significance: This work provides information about previously uncharacterized citrullination sites in synovial fluid fibrinogen from rheumatoid arthritis patients. Detection of these novel citrullination sites may prove to have diagnostic or prognostic value in RA and enhance our understanding of the immune pathogenesis.

AB - Citrullination is a post-translational protein modification, which is associated with inflammation in general and is thought to play an important pathogenic role in rheumatoid arthritis (RA). Here a mass spectrometry-based proteomics approach was applied to identify citrullination sites in synovial fluid fibrinogen from four RA patients. In general, high disease activity correlated with increased number of identified citrullination sites and higher relative citrulline occupancy. Altogether, 23 sites were identified, of which 9 have not been previously reported to be citrullinated in vivo. Citrullination at site α84, α123, α129, α547, α573, α591, β334 and γ134 was identified in more than one patient, and these positions were therefore regarded as hotspots. Following citrullination of fibrinogen in vitro using human recombinant peptidylarginine deiminase 2 (PAD2), a total of 46 citrullination sites were identified, including 6 hitherto unreported in vitro citrullination sites. Twenty-two out of the 23 citrullination sites identified in vivo were also detected in vitro, supporting the validity of the identifications. Significance: This work provides information about previously uncharacterized citrullination sites in synovial fluid fibrinogen from rheumatoid arthritis patients. Detection of these novel citrullination sites may prove to have diagnostic or prognostic value in RA and enhance our understanding of the immune pathogenesis.

U2 - 10.1016/j.jprot.2019.103484

DO - 10.1016/j.jprot.2019.103484

M3 - Journal article

VL - 208

JO - Journal of Proteomics

JF - Journal of Proteomics

SN - 1874-3919

M1 - 103484

ER -