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

被引：9

作者：

Choi, Eun Wha ^{[1
,2
]}

Lee, Kyo Won ^{[3
]}

Park, Hyojun ^{[3
]}

Kim, Hwajung ^{[4
]}

Lee, Jong Hyun ^{[5
]}

Song, Ji Woo ^{[5
,6
]}

Yang, Jehoon ^{[6
]}

Kwon, Yeongbeen ^{[7
]}

Kim, Tae Min ^{[8
,9
]}

Park, Jae Berm ^{[3
]}

Kim, Sungjoo ^{[3
,5
]}

机构：

[1] Kangwon Natl Univ, Coll Vet Med, Dept Vet Clin Pathol, 1 Kangwondaehak Gil, Chuncheon Si 24341, Gangwon Do, South Korea

[2] Kangwon Natl Univ, Inst Vet Sci, 1 Kangwondaehak Gil, Chuncheon Si 24341, Gangwon Do, South Korea

[3] Sungkyunkwan Univ, Div Transplantat, Dept Surg, Sch Med,Samsung Med Ctr, 81 Irwon Ro, Seoul 06351, South Korea

[4] Seoul Natl Univ, Coll Med, Dept Surg, 101 Daehak Ro, Seoul 03080, South Korea

[5] Samsung Med Ctr, Samsung Biomed Res Inst, Transplantat Res Ctr, 81 Irwon Ro, Seoul 06351, South Korea

[6] Samsung Med Ctr, Samsung Biomed Res Inst, Lab Anim Res Ctr, 81 Irwon Ro, Seoul 06351, South Korea

[7] Sungkyunkwan Univ, SAIHST, Dept Hlth Sci & Technol, 81 Irwon Ro, Seoul 06351, South Korea

[8] Seoul Natl Univ, Grad Sch Int Agr Technol, Pyeongchang 25354, Gangwon Do, South Korea

[9] Seoul Natl Univ, Inst Green Bio Sci & Technol, Pyeongchang 25354, Gangwon Do, South Korea

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

关键词：

SYSTEMIC-LUPUS-ERYTHEMATOSUS; COLLAGEN-INDUCED ARTHRITIS; NECROSIS-FACTOR-ALPHA; CD40; LIGAND; DISEASE-ACTIVITY; NUCLEAR-FACTOR; SOLUBLE CD154; ANIMAL-MODELS; PLASMA-LEVELS; T-CELLS;

D O I：

10.1038/s41598-018-20566-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13