The devil in the details: the emerging role of anticitrulline autoimmunity in rheumatoid arthritis.
Rheumatoid arthritis is a chronic inflammatory autoimmune disease of unknown cause. The immune response against citrullinated Ags has recently become the prime suspect for disease pathogenesis. Immunity against citrullinated Ags is thought to play a pivotal role in the disease for several reasons: 1) citrullinated Ags are expressed in the target organ, the inflamed joint; 2) anti-citrullinated protein Abs are present before the disease becomes manifest; and 3) these Abs are highly specific for rheumatoid arthritis. In this review, data from clinical, genetic, biochemical, and animal studies is combined to create a profile of this remarkable autoantibody response. Moreover, a model is proposed of how the anti-citrullinated proteins response is generated and how it could eventually lead to chronic inflammation.
van Gaalen
Floris
F
Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
Ioan-Facsinay
Andreea
A
Huizinga
Tom W J
TW
Toes
René E M
RE
D000936:Antigen-Antibody Complex / Q000502:physiology; D001172:Arthritis, Rheumatoid / Q000209:etiology* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity; D002956:Citrulline / Q000276:immunology*; D006801:Humans; D006867:Hydrolases / Q000502:physiology; D000076342:Protein-Arginine Deiminases
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D002956:Citrulline; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases