Journal article Open Access

Immunity to Citrullinated Proteins in Rheumatoid Arthritis

Klareskog, Lars; Rönnelid, Johan; Lundberg, Karin; Padyukov, Leonid; Alfredsson, Lars

Antibodies to citrullinated proteins (ACPA), i.e., to peptides posttranslationally modified by the conversion of arginine to citrulline, are specific serological markers for rheumatoid arthritis (RA). Studies on anticitrulline immunity, summarized in this review, demonstrate that the criterion-based syndrome RA should be subdivided into at least two distinct subsets (ACPA-positive and ACPA-negative disease). A new etiological model is proposed for ACPA-positive RA, built on MHC class II–dependent activation of adaptive immunity. Fundamentals of this model include the following: (a) ACPA antedate onset of arthritis; (b) ACPA may aggravate arthritis in rodents; (c) ACPA are triggered in the context of genes that confer susceptibility to RA (HLA-DRB1 SE) and by environmental agents triggering RA (smoking or bacterial stimuli); (d) ACPA may complex with citrullinated proteins present in target tissue as part of a multistep process for arthritis development. The model provides a new basis for molecular studies on the pathogenesis of ACPA-positive arthritis.

Files (516.0 kB)
Name Size
article.pdf
md5:7e22708c275bab04aeadd018594e9f7f
516.0 kB Download
28
31
views
downloads
Views 28
Downloads 31
Data volume 16.0 MB
Unique views 28
Unique downloads 31

Share

Cite as