title: Carbamylation and antibodies against carbamylated proteins in autoimmunity and other pathologies.
abstract: Carbamylation is a non-enzymatic post-translational modification in which cyanate binds to molecules containing primary amine or thiol groups and forms carbamyl groups. Cyanate is in equilibrium with urea in body fluid and increased carbamylation was first reported in patients with increased urea levels such as patients suffering renal diseases. Next, increased carbamylation related to inflammation has also been described in other conditions such as cardiovascular disease. Recently, a new consequence of carbamylation has been observed: induction of an autoantibody response. We identified anti-carbamylated protein (anti-CarP) antibodies in rheumatoid arthritis (RA) patients and in patients having 'pre-RA' symptoms, arthralgia. The presence of anti-CarP antibodies in arthralgia patients is associated with an increased risk of developing RA. The presence of anti-CarP antibodies in RA patients is associated with more severe joint damage in RA patients who do not have anti-citrullinated protein antibodies. It is currently unknown to what extent carbamylation and/or the formation of anti-CarP antibodies contributes to the disease processes of chronic diseases such as renal diseases, cardiovascular diseases and RA. This review summarizes the current knowledge on carbamylation and the formation of anti-CarP antibodies and discusses their possibly important implications.
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: j.shi@lumc.nl.
authors.forename: Jing
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: p.a.van_veelen@lumc.nl.
authors.forename: Peter A
authors.initials: PA
authors.lastname: van Veelen
authors.affiliation: INOVA Diagnostics, Inc., San Diego, CA, USA. Electronic address: mmahler@inovadx.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Mahler
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: G.M.C.Janssen@lumc.nl.
authors.forename: George M C
authors.initials: GM
authors.lastname: Janssen
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: J.W.Drijfhout@lumc.nl.
authors.forename: Jan W
authors.initials: JW
authors.lastname: Drijfhout
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: T.W.J.Huizinga@lumc.nl.
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: R.E.M.Toes@lumc.nl.
authors.forename: Rene E M
authors.initials: RE
authors.lastname: Toes
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: l.a.trouw@lumc.nl.
authors.forename: Leendert A
authors.initials: LA
authors.lastname: Trouw
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D002219:Carbamates / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000276:immunology*
chemical_list: D000906:Antibodies; D002219:Carbamates; D011506:Proteins; C070766:carbamic acid
keywords: Anti-carbamylated protein antibodies; Carbamylation; Cardiovascular diseases; Cataract; Chronic kidney diseases; Rheumatoid arthritis