New vaccinal strategy to prevent or treat rheumatoid arthritis

The present invention relates to field of treatment of rheumatoid arthritis. The inventors propose that PAD4, one of the enzymes which convert arginine into citrulline, is a target antigen for T cells that help the production of ACPA. They recently demonstrated that PAD immunization triggers anti-citrullinated fibrinogen antibody production in normal mice. Here, they demonstrate that the risk (OR) to develop RA associated with each of 12 HLA-DRB1 genotype correlates with the likelihood for the two HLA-DR molecules encoded by each genotype to bind at least one random peptide from PAD4, but not from citrullinated or native fibrinogen. PBLs from patients wih RA, PsA and controls proliferate to PAD4 and they identify, notably, a peptide from PAD4, p8 (SEQ ID NO: 6), that stimulates T cells from RA patients and a few patients with PsA. Proliferative responses to p8 are associated with RA, shared epitope positive HLA-DR alleles and antibodies to PAD4. Thus the present invention relates to a peptide derived from the PAD4 protein and its use in the treatment and prevention of rheumatoid arthritis.

Keywords: Rheumatoid arthritis, Vaccine, PAD4
Patent Application number: European Procedure (Patents) (EPA) - 07 Mars 2019 - 19 305 265.1
Inventors:
ROUDIER Jean,AUGER Isabelle,BALANDRAUD Nathalie
Publications:
Arthritis Rheumatol. 2020 Jun;72(6):903-911. doi: 10.1002/art.41189. Epub 2020 Apr 26

Proc Natl Acad Sci USA. 2017 Nov 21;114(47):E10169-E10177. doi: 10.1073/pnas.1713112114. Epub 2017 Nov 6.

Reference:

BIO19058-T1

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Patent filling date: 2020-03-06

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