Inhibitory effect of CD147/HAb18 monoclonal antibody on cartilage erosion and synovitis in the SCID mouse model for rheumatoid arthritis.
OBJECTIVE
To explore the therapeutic potential of CD147/HAb18 mAb in the treatment of RA in severe combined immunodeficiency (SCID) mice engrafted with human cartilage and rheumatoid synovium tissue (SCID-HuRAg).


METHODS
SCID-HuRAg mice were treated separately with CD147/HAb18 mAb, anti-TNF-alpha mAb or a combination of both. The mice in control group were treated with anti-Japanese encephalitis virus mAb. The volume of engrafts was measured and the number of inflammatory cells and cartilage erosion score were examined. Expression of MMP-2, -3 and -9 was determined by immunohistochemistry. Human inflammatory cytokine levels in mouse sera were assessed using cytometric bead array kit.


RESULTS
The volume of engrafts decreased significantly in SCID-HuRAg mice treated separately with anti-CD147 mAb or anti-TNF-alpha mAb, and in the mice treated with anti-CD147 mAb plus anti-TNF-alpha mAb (P < 0.05). Significant reduction was observed in cartilage erosion score in anti-CD147 treatment group and combined treatment group (P < 0.05). Immunohistochemical analysis showed that expression of MMP-2, -3 and -9 was lower in the anti-CD147 treatment group and combined treatment group than in the control mAb group (P < 0.05). Moreover, the level of TNF-alpha, IL-6 and -8 in CD147 mAb group showed a significant decrease compared with that of the control mAb group (P < 0.05).


CONCLUSIONS
CD147/HAb18 mAb can reduce cartilage erosion and synovitis by inhibition of the MMPs and reduction of inflammatory cytokines in SCID-HuRAg mice, which suggests that CD147/HAb18 mAb is a promising treatment option for RA patients.
Department of Clinical Immunology, State Key Discipline of Cell Biology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, PR of China.
Junfeng
J
Jia
Conghua
C
Wang
Zhanguo
Z
Shi
Jingkang
J
Zhao
Yun
Y
Jia
Zheng
Z
Zhao-Hui
Xiaoyan
X
Li
Zhinan
Z
Chen
Ping
P
Zhu
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D051926:Basigin / Q000276:immunology*; D002358:Cartilage, Articular / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D023421:Models, Animal; D013583:Synovial Membrane / Q000276:immunology / Q000473:pathology / Q000637:transplantation; D013585:Synovitis / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D016207:Cytokines; D051926:Basigin; D020782:Matrix Metalloproteinases