Therapeutic study of rheumatoid arthritis by humanized anti-PAD4 antibody

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461470
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Nagoya City University
• Principal Investigator: KANAZAWA Satoshi 名古屋市立大学, 大学院医学研究科, 助教 (90347401)
• Co-Investigator(Renkei-kenkyūsha): SATO Mamoru 横浜市立大学, 大学院生命医科学研究科, 教授 (60170784)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 関節リウマチ / 間質性肺炎 / PAD4 / 抗CCP抗体 / 炎症 / トランスレーショナルリサーチ / モデル動物

Outline of Final Research Achievements

Peptidylarginine deiminase 4 (PAD4) that catalyzes the conversion of protein arginine residues to citrulline residues in the presence of Ca2+ is likely to be involved in rheumatoid arthritis (RA), because anti cyclic citrullinated protein antibodies against its catalytic modified peptides are associated with onset of RA disease. However, it is still not clear whether PAD4, in particular, its catalytic activity directly affects onset of RA symptoms.　To reveal this, we created that anti PAD4 monoclonal antibodies recognized catalytic cleft of PAD4. Antibodies were obtained by phage display technique to be combined with immunization in chick.　They were introduced by intraperitoneal administration in RA model mouse, called D1CC mouse, resulted in reduction of onset of inflammatory arthritis.　Anti PAD4 antibody reduces inflammatory arthritis in D1CC mouse. We therefore concluded that PAD4 played critical role in the pathogenesis of initial phase of RA.

Free Research Field

免疫学