PT  - JOURNAL ARTICLE
AU  - Kampstra, Arieke Suzanna Berendina
AU  - Dekkers, Jacqueline Stephanie
AU  - Volkov, Mikhail
AU  - Dorjée, Annemarie L
AU  - Hafkenscheid, Lise
AU  - Kempers, Ayla C
AU  - van Delft, Myrthe
AU  - Kissel, Theresa
AU  - Reijm, Sanne
AU  - Janssen, George M C
AU  - van Veelen, Peter A
AU  - Bang, Holger
AU  - Huizinga, Tom W J
AU  - Trouw, Leendert A
AU  - van der Woude, Diane
AU  - Toes, René E M
TI  - Different classes of anti-modified protein antibodies are induced on exposure to antigens expressing only one type of modification
AID  - 10.1136/annrheumdis-2018-214950
DP  - 2019 Jul 01
TA  - Annals of the Rheumatic Diseases
PG  - 908--916
VI  - 78
IP  - 7
4099  - http://ard.bmj.com/content/78/7/908.short
4100  - http://ard.bmj.com/content/78/7/908.full
SO  - Ann Rheum Dis2019 Jul 01; 78
AB  - Objectives Autoantibodies against post-translationally modified proteins (anti-modified protein antibodies or AMPAs) are a hallmark of rheumatoid arthritis (RA). A variety of classes of AMPAs against different modifications on proteins, such as citrullination, carbamylation and acetylation, have now been described in RA. At present, there is no conceptual framework explaining the concurrent presence or mutual relationship of different AMPA responses in RA. Here, we aimed to gain understanding of the co-occurrence of AMPA by postulating that the AMPA response shares a common ‘background’ that can evolve into different classes of AMPAs.Methods Mice were immunised with modified antigens and analysed for AMPA responses. In addition, reactivity of AMPA purified from patients with RA towards differently modified antigens was determined.Results Immunisation with carbamylated proteins induced AMPAs recognising carbamylated proteins and also acetylated proteins. Similarly, acetylated proteins generated (autoreactive) AMPAs against other modifications as well. Analysis of anti-citrullinated protein antibodies from patients with RA revealed that these also display reactivity to acetylated and carbamylated antigens. Similarly, anti-carbamylated protein antibodies showed cross-reactivity against all three post-translational modifications.Conclusions Different AMPA responses can emerge from exposure to only a single type of modified protein. These findings indicate that different AMPA responses can originate from a common B-cell response that diversifies into multiple distinct AMPA responses and explain the presence of multiple AMPAs in RA, one of the hallmarks of the disease.