CD81 inhibition with the cytoplasmic RNA vector producing anti-CD81 antibodies suppresses arthritis in a rat CIA model

• Published in: Biochemical and biophysical research communications Vol. 604; pp. 22 - 29
• Main Authors: Fujii, Yuta, Arai, Yuji, Nakagawa, Shuji, Yamasaki, Tsutomu, Iijima, Minoru, Yamada, Naofumi, Takahashi, Kenji, Nakanishi, Mahito, Nakanishi, Tohru
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.05.2022
• Subjects: Animals; Arthritis, Experimental - drug therapy; Arthritis, Rheumatoid - pathology; Cartilage, Articular - metabolism; CD81 inhibition; CIA model; Cytoplasmic RNA vector; Rats; Rheumatoid arthritis; RNA - metabolism; Synovial Membrane - pathology; PBS; Cytoplasmic RNA vector; SD; Rheumatoid arthritis; CIA model; CD81 inhibition; CIA; ELISA; RA
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2022.02.081

Cluster of differentiation 81 (CD81) is a tetraspanin membrane protein consisting of 4 transmembrane domains and 2 outer membrane loops. CD81 inhibition is a potential treatment for rheumatoid arthritis (RA). Here, we investigated the therapeutic effects of the cytoplasmic RNA vector expressing anti-CD81 antibodies (the anti-CD81 vector) on the ankle joint synovium in collagen-induced arthritis (CIA) rats. Body weight, paw volume, and clinical scores were measured on days 0, 7, and 10 and daily thereafter. On day 28, the ankle joints of the rats were removed and stained with haematoxylin, eosin, and Safranin O. Arthritic changes such as inflammatory cell infiltration, synovial proliferation, articular cartilage destruction, and bone erosion were evaluated by histological scoring. Symptom onset was delayed in the right lower limbs of the rats administered the cytoplasmic RNA vector (CIA + anti-CD81) compared with that in the control group (CIA + control). The CIA + anti-CD81 rats were heavier than the CIA + control rats. The paw volume and clinical scores were significantly lower in the CIA + anti-CD81 than in the CIA + control. The histological scores indicated significantly milder manifestations of RA in the CIA + anti-CD81 than in the CIA + control. Administration of the cytoplasmic RNA vector expressing anti-CD81 antibodies suppressed arthritis and joint destruction in CIA rats. Our findings suggest that the cytoplasmic RNA vector can be used to treat RA. •The cytoplasmic RNA vectors were localized to infect the joint synovium.•These results provide new insights into treatment for localized joints in rheumatoid arthritis.•These results perhaps hope for the many people around the world affected by RA.