Citrullination is an inflammation‐dependent process
Department of Medicine, Rheumatology Unit, CMM, L8‐04, Karolinska University Hospital, Solna, S‐17176 Stockholm, Sweden; Anca.Catrina@ki.se
Department of Medicine, Rheumatology Unit, CMM, L8‐04, Karolinska University Hospital, Solna, S‐17176 Stockholm, Sweden; Anca.Catrina@ki.se
Abstract
Objectives
To study the presence of citrullinated proteins in inflammatory conditions and in clinically non‐affected tissues of controls.
Methods
Synovial biopsy specimens from 19 patients with rheumatoid arthritis and 10 healthy controls were investigated by immunohistochemistry. Additionally, muscle tissue from 5 patients with polymyositis and from 7 healthy controls, intestinal tissue from macroscopically affected and non‐affected areas from 10 patients with inflammatory bowel disease (IBD) and tonsil tissues from 4 chronically inflamed tonsils were studied.
Results
Citrullinated proteins were present in all synovial biopsy specimens from patients with rheumatoid arthritis, whereas only three of 10 healthy synovial biopsy specimens showed scarce amounts of citrullination. Citrullination was also present in all myositis‐affected muscles, whereas it was absent in the muscle tissues of controls. All tonsil biopsy specimens studied were positive for citrulline. Even though more frequently detected in the macroscopically affected colonic areas, no marked difference was observed in the pattern or extent of citrullination between the macroscopically affected and non‐affected intestinal IBD tissues.
Conclusion
Citrullination is present in a wide range of inflammatory tissues, suggesting that this process is inflammation dependent rather than disease dependent.
Rheumatoid arthritis is an inflammatory disease that is characterised by the presence of antibodies against citrullinated peptides that may have an important role in the pathogenesis of rheumatoid arthritis.1 Citrullination represents the calcium‐dependent conversion of peptidylarginine to peptidylcitrulline, which is catalysed by peptidylarginine deiminase (PAD) enzymes. This enzymatic conversion normally occurs in processes such as epidermal differentiation,2 formation of the hair follicle3 and differentiation of the myelin sheath during development of the central nervous system.4 The presence of citrullinated proteins was initially considered specific to the synovium in patients with rheumatoid arthritis.5 However, recent reports showed that citrullinated proteins are also present in non‐rheumatoid arthritis inflammatory synovitis,67 suggesting that citrullination of specific antigenic targets rather than citrullination as such is a disease‐specific process. Moreover, citrullination occurs in autoimmune neurodegenerative diseases such as multiple sclerosis48 and Alzheimer's disease.9 In the light of these observations, we asked whether citrullination occurs in types of inflammation other than arthritis and to what extent citrullination is present in the normal joint. To investigate this, we evaluated the presence of citrullinated proteins in inflamed and non‐inflamed tissues.
Acknowledgements
We thank Marianne Engström for excellent technical assistance. This study was supported by grants from the Swedish Medical Research Council, the Swedish Rheumatism Association, the Insurance Company AFA, the The King Gustav V's 80 years Foundation, and the Söderberg Foundation.
Abbreviations
IBD - inflammatory bowel disease
PAD - peptidylarginine deiminase
Footnotes
Competing interests: None declared.
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