Citrullination in extra-articular manifestations of rheumatoid arthritis

Tim Bongartz, T. Cantaert, S. R. Atkins, P. Harle, J. L. Myers, C. Turesson, Jay H Ryu, D. Baeten, Eric Lawrence Matteson

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Abstract

Background. Anti-citrullinated protein antibodies have been detected with high specificity in serum of patients with rheumatoid arthritis (RA), and citrullination of proteins may play a key role in the pathogenesis of RA. We therefore investigated the presence of citrullination in two extra-articular manifestations of RA, interstitial pneumonia (IP) and rheumatoid nodules. Methods. Open-lung biopsy specimens from patients with RA-associated IP (n = 18), idiopathic IP (n = 20) and controls (n = 10), as well as specimens of rheumatoid nodules from 26 patients, were examined. All sections were incubated with an anti-modified citrulline antibody. Masked scoring of stained sections and analysis of results by stratification according to demographic and clinical characteristics was performed. Results. Presence of citrulline could be detected in eight lung specimens of patients with RA-associated IP (44%) and nine patients with idiopathic IP (46%). Conversely, lung tissue from control patients showed weak extracellular citrullination in only two cases (20%). Citrullination did not show any significant associations with demographic or clinical characteristics such as age, gender, smoking habits, disease severity, histological subtype, degree of inflammation or steroid use. Rheumatoid nodules were citrulline positive in a majority of cases (70%). Conclusion. Citrullination is present in extra-articular manifestations of RA such as IP and nodules. In contrast to the high specificity of anti-citrulline antibodies in RA, citrullination is not only restricted to RA but can also be observed in idiopathic IP. Whether citrullination significantly contributes to the initiation or perpetuation of autoimmunity or merely reflects ongoing inflammation remains to be clarified.

Original languageEnglish (US)
Pages (from-to)70-75
Number of pages6
JournalRheumatology
Volume46
Issue number1
DOIs
StatePublished - Jan 2007

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Rheumatoid Arthritis
Joints
Citrulline
Idiopathic Interstitial Pneumonias
Rheumatoid Nodule
Interstitial Lung Diseases
Lung
Demography
Inflammation
Antibodies
Autoimmunity
Habits
Anti-Idiotypic Antibodies
Proteins
Smoking
Steroids
Biopsy
Serum

Keywords

  • Citrullination
  • Extra-articular disease
  • Interstitial pneumonia
  • Rheumatoid arthritis
  • Rheumatoid nodules

ASJC Scopus subject areas

  • Neuroscience(all)
  • Rheumatology

Cite this

Bongartz, T., Cantaert, T., Atkins, S. R., Harle, P., Myers, J. L., Turesson, C., ... Matteson, E. L. (2007). Citrullination in extra-articular manifestations of rheumatoid arthritis. Rheumatology, 46(1), 70-75. https://doi.org/10.1093/rheumatology/kel202

Citrullination in extra-articular manifestations of rheumatoid arthritis. / Bongartz, Tim; Cantaert, T.; Atkins, S. R.; Harle, P.; Myers, J. L.; Turesson, C.; Ryu, Jay H; Baeten, D.; Matteson, Eric Lawrence.

In: Rheumatology, Vol. 46, No. 1, 01.2007, p. 70-75.

Research output: Contribution to journalArticle

Bongartz, T, Cantaert, T, Atkins, SR, Harle, P, Myers, JL, Turesson, C, Ryu, JH, Baeten, D & Matteson, EL 2007, 'Citrullination in extra-articular manifestations of rheumatoid arthritis', Rheumatology, vol. 46, no. 1, pp. 70-75. https://doi.org/10.1093/rheumatology/kel202
Bongartz T, Cantaert T, Atkins SR, Harle P, Myers JL, Turesson C et al. Citrullination in extra-articular manifestations of rheumatoid arthritis. Rheumatology. 2007 Jan;46(1):70-75. https://doi.org/10.1093/rheumatology/kel202
Bongartz, Tim ; Cantaert, T. ; Atkins, S. R. ; Harle, P. ; Myers, J. L. ; Turesson, C. ; Ryu, Jay H ; Baeten, D. ; Matteson, Eric Lawrence. / Citrullination in extra-articular manifestations of rheumatoid arthritis. In: Rheumatology. 2007 ; Vol. 46, No. 1. pp. 70-75.
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title = "Citrullination in extra-articular manifestations of rheumatoid arthritis",
abstract = "Background. Anti-citrullinated protein antibodies have been detected with high specificity in serum of patients with rheumatoid arthritis (RA), and citrullination of proteins may play a key role in the pathogenesis of RA. We therefore investigated the presence of citrullination in two extra-articular manifestations of RA, interstitial pneumonia (IP) and rheumatoid nodules. Methods. Open-lung biopsy specimens from patients with RA-associated IP (n = 18), idiopathic IP (n = 20) and controls (n = 10), as well as specimens of rheumatoid nodules from 26 patients, were examined. All sections were incubated with an anti-modified citrulline antibody. Masked scoring of stained sections and analysis of results by stratification according to demographic and clinical characteristics was performed. Results. Presence of citrulline could be detected in eight lung specimens of patients with RA-associated IP (44{\%}) and nine patients with idiopathic IP (46{\%}). Conversely, lung tissue from control patients showed weak extracellular citrullination in only two cases (20{\%}). Citrullination did not show any significant associations with demographic or clinical characteristics such as age, gender, smoking habits, disease severity, histological subtype, degree of inflammation or steroid use. Rheumatoid nodules were citrulline positive in a majority of cases (70{\%}). Conclusion. Citrullination is present in extra-articular manifestations of RA such as IP and nodules. In contrast to the high specificity of anti-citrulline antibodies in RA, citrullination is not only restricted to RA but can also be observed in idiopathic IP. Whether citrullination significantly contributes to the initiation or perpetuation of autoimmunity or merely reflects ongoing inflammation remains to be clarified.",
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AU - Cantaert, T.

AU - Atkins, S. R.

AU - Harle, P.

AU - Myers, J. L.

AU - Turesson, C.

AU - Ryu, Jay H

AU - Baeten, D.

AU - Matteson, Eric Lawrence

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N2 - Background. Anti-citrullinated protein antibodies have been detected with high specificity in serum of patients with rheumatoid arthritis (RA), and citrullination of proteins may play a key role in the pathogenesis of RA. We therefore investigated the presence of citrullination in two extra-articular manifestations of RA, interstitial pneumonia (IP) and rheumatoid nodules. Methods. Open-lung biopsy specimens from patients with RA-associated IP (n = 18), idiopathic IP (n = 20) and controls (n = 10), as well as specimens of rheumatoid nodules from 26 patients, were examined. All sections were incubated with an anti-modified citrulline antibody. Masked scoring of stained sections and analysis of results by stratification according to demographic and clinical characteristics was performed. Results. Presence of citrulline could be detected in eight lung specimens of patients with RA-associated IP (44%) and nine patients with idiopathic IP (46%). Conversely, lung tissue from control patients showed weak extracellular citrullination in only two cases (20%). Citrullination did not show any significant associations with demographic or clinical characteristics such as age, gender, smoking habits, disease severity, histological subtype, degree of inflammation or steroid use. Rheumatoid nodules were citrulline positive in a majority of cases (70%). Conclusion. Citrullination is present in extra-articular manifestations of RA such as IP and nodules. In contrast to the high specificity of anti-citrulline antibodies in RA, citrullination is not only restricted to RA but can also be observed in idiopathic IP. Whether citrullination significantly contributes to the initiation or perpetuation of autoimmunity or merely reflects ongoing inflammation remains to be clarified.

AB - Background. Anti-citrullinated protein antibodies have been detected with high specificity in serum of patients with rheumatoid arthritis (RA), and citrullination of proteins may play a key role in the pathogenesis of RA. We therefore investigated the presence of citrullination in two extra-articular manifestations of RA, interstitial pneumonia (IP) and rheumatoid nodules. Methods. Open-lung biopsy specimens from patients with RA-associated IP (n = 18), idiopathic IP (n = 20) and controls (n = 10), as well as specimens of rheumatoid nodules from 26 patients, were examined. All sections were incubated with an anti-modified citrulline antibody. Masked scoring of stained sections and analysis of results by stratification according to demographic and clinical characteristics was performed. Results. Presence of citrulline could be detected in eight lung specimens of patients with RA-associated IP (44%) and nine patients with idiopathic IP (46%). Conversely, lung tissue from control patients showed weak extracellular citrullination in only two cases (20%). Citrullination did not show any significant associations with demographic or clinical characteristics such as age, gender, smoking habits, disease severity, histological subtype, degree of inflammation or steroid use. Rheumatoid nodules were citrulline positive in a majority of cases (70%). Conclusion. Citrullination is present in extra-articular manifestations of RA such as IP and nodules. In contrast to the high specificity of anti-citrulline antibodies in RA, citrullination is not only restricted to RA but can also be observed in idiopathic IP. Whether citrullination significantly contributes to the initiation or perpetuation of autoimmunity or merely reflects ongoing inflammation remains to be clarified.

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KW - Interstitial pneumonia

KW - Rheumatoid arthritis

KW - Rheumatoid nodules

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