RT Journal Article
SR Electronic
T1 Different classes of anti-modified protein antibodies are induced on exposure to antigens expressing only one type of modification
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 908
OP 916
DO 10.1136/annrheumdis-2018-214950
VO 78
IS 7
A1 Kampstra, Arieke Suzanna Berendina
A1 Dekkers, Jacqueline Stephanie
A1 Volkov, Mikhail
A1 Dorjée, Annemarie L
A1 Hafkenscheid, Lise
A1 Kempers, Ayla C
A1 van Delft, Myrthe
A1 Kissel, Theresa
A1 Reijm, Sanne
A1 Janssen, George M C
A1 van Veelen, Peter A
A1 Bang, Holger
A1 Huizinga, Tom W J
A1 Trouw, Leendert A
A1 van der Woude, Diane
A1 Toes, René E M
YR 2019
UL http://ard.bmj.com/content/78/7/908.abstract
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.