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Sci Rep. 2018 Feb 1;8(1):2135. doi: 10.1038/s41598-018-20566-z.

Therapeutic effects of anti-CD154 antibody in cynomolgus monkeys with advanced rheumatoid arthritis.

Author information

1
Department of Veterinary Clinical Pathology, College of Veterinary Medicine & Institute of Veterinary Science, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon-si, Gangwon-do, 24341, Republic of Korea. ewchoi@kangwon.ac.kr.
2
Department of Surgery, Division of Transplantation, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
3
Department of Surgery, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.
4
Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
5
Laboratory Animal Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
6
Department of Health Science and Technology, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea.
7
Graduate School of International Agricultural Technology and Institute of Green-Bio Science and Technology, Seoul National University, Pyeongchang, Gangwon-do, 25354, South Korea.
8
Department of Surgery, Division of Transplantation, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea. kmhyj111@gmail.com.
9
Transplantation Research Center, Samsung Biomedical Research Institute, Samsung Medical Center, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Republic of Korea. kmhyj111@gmail.com.

Abstract

Rheumatoid arthritis is one major chronic inflammatory systemic autoimmune disease. The CD154-CD40 interactions play a critical role in the regulation of immune responses and the maintenance of autoimmunity. Therefore, we aimed to determine whether anti-CD154 antibody treatment show positive effects on immunomodulation and clinical improvement of sustained severe rheumatoid arthritis in cynomolgus monkeys. Arthritis was induced using chicken type II collagen (CII) and arthritic monkey were divided into control and anti-CD154 treatment groups based on their concentrations of anti-CII antibodies on week 7 post-immunization. Blood and tissue samples were collected on week 16 post-immunization. Anti-CD154 antibody treatment improved arthritis and movement, and significantly decreased the numbers of proliferating B cells and the serum levels of anti-type II collagen antibody and sCD154 compared with non-treatment group. Further anti-CD154 antibody treatment significantly decreased the percentage of CD4+ cells and the ratio of CD4+ to CD8+ T cells and significantly increased the percentage of CD8+ cells and effector memory CD8+ cells in peripheral blood. We have shown for the first time in a nonhuman primate model of RA that CD154 blockade has beneficial effects. This study might be valuable as preclinical data of CD154 blockade in nonhuman primate models of severe rheumatoid arthritis.

PMID:
29391506
PMCID:
PMC5794761
DOI:
10.1038/s41598-018-20566-z
[Indexed for MEDLINE]
Free PMC Article

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