TY - JOUR
T1 - Insights into the study and origin of the citrullinome in rheumatoid arthritis
AU - Fert-Bober, Justyna
AU - Darrah, Erika
AU - Andrade, Felipe
N1 - Funding Information:
ED and FA are authors on licensed patent no. 8,975,033, entitled "Human autoantibodies specific for PAD3 which are cross‐reactive with PAD4 and their use in the diagnosis and treatment of rheumatoid arthritis and related diseases” and on provisional patient no. 62/481,158 entitled “Anti‐PAD2 antibody for treating and evaluating rheumatoid arthritis.” FA serves as consultant for Bristol‐Myers Squibb, has received a grant from MedImmune, and has received personal fees from Celgene, outside of this submitted work. ED has received a grant from Pfizer, Celgene, and MedImmune and personal fees from Celgene, outside of this submitted work. The remaining authors declare no competing interests.
Funding Information:
Funding for this project was provided by the Jerome L. Greene Foundation, Rheumatology Research Foundation, and the National Institutes of Health (NIH) grants number R01 AR069569, R050026‐12A1, and R01HL111362. The content of this paper is solely the responsibility of the author and does not represent the official views of the NIH.
Funding Information:
Funding for this project was provided by the Jerome L. Greene Foundation, Rheumatology Research Foundation, and the National Institutes of Health (NIH) grants number R01 AR069569, R050026-12A1, and R01HL111362. The content of this paper is solely the responsibility of the author and does not represent the official views of the NIH.
Publisher Copyright:
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2020/3/1
Y1 - 2020/3/1
N2 - The presence of autoantibodies and autoreactive T cells to citrullinated proteins and citrullinating enzymes in patients with rheumatoid arthritis (RA), together with the accumulation of citrullinated proteins in rheumatoid joints, provides substantial evidence that dysregulated citrullination is a hallmark feature of RA. However, understanding mechanisms that dysregulate citrullination in RA has important challenges. Citrullination is a normal process in immune and non-immune cells, which is likely activated by different conditions (eg, inflammation) with no pathogenic consequences. In a complex inflammatory environment such as the RA joint, unique strategies are therefore required to dissect specific mechanisms involved in the abnormal production of citrullinated proteins. Here, we will review current models of citrullination in RA and discuss critical components that, in our view, are relevant to understanding the accumulation of citrullinated proteins in the RA joint, collectively referred to as the RA citrullinome. In particular, we will focus on potential caveats in the study of citrullination in RA and will highlight methods to precisely detect citrullinated proteins in complex biological samples, which is a confirmatory approach to mechanistically link the RA citrullinome with unique pathogenic pathways in RA.
AB - The presence of autoantibodies and autoreactive T cells to citrullinated proteins and citrullinating enzymes in patients with rheumatoid arthritis (RA), together with the accumulation of citrullinated proteins in rheumatoid joints, provides substantial evidence that dysregulated citrullination is a hallmark feature of RA. However, understanding mechanisms that dysregulate citrullination in RA has important challenges. Citrullination is a normal process in immune and non-immune cells, which is likely activated by different conditions (eg, inflammation) with no pathogenic consequences. In a complex inflammatory environment such as the RA joint, unique strategies are therefore required to dissect specific mechanisms involved in the abnormal production of citrullinated proteins. Here, we will review current models of citrullination in RA and discuss critical components that, in our view, are relevant to understanding the accumulation of citrullinated proteins in the RA joint, collectively referred to as the RA citrullinome. In particular, we will focus on potential caveats in the study of citrullination in RA and will highlight methods to precisely detect citrullinated proteins in complex biological samples, which is a confirmatory approach to mechanistically link the RA citrullinome with unique pathogenic pathways in RA.
KW - ACPA
KW - citrullination
KW - mass spectrometry
KW - neutrophil extracellular traps
KW - peptidylarginine deiminase
KW - rheumatoid arthritis
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U2 - 10.1111/imr.12834
DO - 10.1111/imr.12834
M3 - Review article
C2 - 31876028
AN - SCOPUS:85077155179
SN - 0105-2896
VL - 294
SP - 133
EP - 147
JO - Immunological reviews
JF - Immunological reviews
IS - 1
ER -