Antibodies to citrullinated proteins: molecular interactions and arthritogenicity
- 23 December 2009
- journal article
- review article
- Published by Wiley in Immunological Reviews
- Vol. 233 (1), 9-33
- https://doi.org/10.1111/j.0105-2896.2009.00853.x
Abstract
The discovery of antibodies specific for citrullinated protein epitopes [anti-citrullinated protein antibodies (ACPAs)] is a hallmark for the diagnosis and prognosis of rheumatoid arthritis (RA) and will also be a useful tool for understanding the fundamental pathologic processes. There are several essential questions pertaining to ACPA that remain to be explored, such as understanding the early specificity of the underlying T-cell recognition, whether the production of ACPA is a primary or secondary process, and in the event of such antibodies being arthritogenic, whether they could possibly regulate the disease development. To answer these questions, animal models are needed, but unfortunately ACPA is not a prominent feature of any of the classical animal models of RA. However, we showed recently that ACPA can be isolated from animals susceptible to collagen-induced arthritis that are specific for citrullinated type II collagen (CII). The citrulline specificity could be visualized, and the specificity is determined primarily by a direct interaction with citrulline. We also demonstrated that these antibodies are specific for the citrullinated epitopes and are pathogenic in vivo. A new hypothesis to explain how inflammation in RA can be directed to cartilaginous joints and be self-perpetuating is suggested, which involves recognition of post-translational modifications (glycosylation and citrullination) on CII by T and B cells that can have both arthritogenic and regulatory consequences.Keywords
This publication has 226 references indexed in Scilit:
- Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formationThe Journal of cell biology, 2009
- Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid arthritis and periodontitisInternational Immunopharmacology, 2008
- Initiation of the alternative pathway of murine complement by immune complexes is dependent on N‐glycans in IgG antibodiesArthritis & Rheumatism, 2008
- Positional cloning of the Igl genes controlling rheumatoid factor production and allergic bronchitis in ratsProceedings of the National Academy of Sciences of the United States of America, 2008
- Two independent alleles at 6q23 associated with risk of rheumatoid arthritisNature Genetics, 2007
- Profiling Protein Arginine Deiminase 4 (PAD4): A novel screen to identify PAD4 inhibitorsBioorganic & Medicinal Chemistry, 2007
- Blocking of experimental arthritis by cleavage of IgG antibodies in vivoArthritis & Rheumatism, 2007
- Multimerized T cell epitopes protect from experimental autoimmune diabetes by inducing dominant toleranceProceedings of the National Academy of Sciences of the United States of America, 2007
- T cell surface redox levels determine T cell reactivity and arthritis susceptibilityProceedings of the National Academy of Sciences, 2006
- Minocycline inhibits poly(ADP-ribose) polymerase-1 at nanomolar concentrationsProceedings of the National Academy of Sciences, 2006