Abstract
The objective of this study is to evaluate the efficacy and potential mechanism of action of type-II collagen bifunctional peptide inhibitor (CII-BPI) molecules in suppressing rheumatoid arthritis in the collagen-induced arthritis (CIA) mouse model. CII-BPI molecules (CII-BPI-1, CII-BPI-2, and CII-BPI-3) were formed through conjugation between an antigenic peptide derived from type-II collagen and a cell adhesion peptide LABL (CD11a237-246) from the I-domain of LFA-1 via a linker molecule. The hypothesis is that the CII-BPI molecules simultaneously bind to MHC-II and ICAM-1 on the surface of APC and block maturation of the immunological synapse. As a result, the differentiation of naïve T cells is altered from inflammatory to regulatory and/or suppressor T cells. The efficacies of CII-BPI molecules were evaluated upon intravenous injections in CIA mice. Results showed that CII-BPI-1 and CIIBPI-2 suppressed the joint inflammations in CIA mice in a dose-dependent manner and were more potent than the respective antigenic peptides alone. CII-BPI-3 was not as efficacious as CII-BPI-1 and CII-BPI-2. Significantly less joint damage was observed in CII-BPI-2 and CII-2 treated mice than in the control. The production of IL-6 was significantly lower at the peak of disease in mice treated with CII-BPI-2 compared to those treated with CII-2 and control. In conclusion, this is the first proof-of-concept study showing that BPI molecules can be used to suppress RA and may be a potential therapeutic strategy for the treatment of rheumatoid arthritis.
Highlights
Rheumatoid Arthritis (RA) is an autoimmune disease that causes pain, stiffness, chronic inflammation, and deformity due to cartilage, bone, and ligament destruction in the joints [1]
Changes in paw volume due to swelling were significantly lower in consists mainly of type II (CII)-Bifunctional Peptide Inhibitor (BPI)-1-treated mice than in those treated with PBS (Figure 1A; p
Auto-reactive T cells have been implicated in the onset and progression of autoimmune diseases, including multiple sclerosis (MS), type-1 diabetes (T1D), and rheumatoid arthritis (RA)
Summary
Rheumatoid Arthritis (RA) is an autoimmune disease that causes pain, stiffness, chronic inflammation, and deformity due to cartilage, bone, and ligament destruction in the joints [1]. Th17 cells, a subset of Th cells, have been implicated in autoimmune diseases, including rheumatoid arthritis [3,7]. Another possible cause is that the body fails to activate regulatory T cells (T-reg); enhancing the production of T-reg may be one therapeutic strategy to suppress RA and other autoimmune diseases [8,9,10,11,12]. Methotrexate is one of the most commonly used traditional DMARD It is effective, its use is sometimes discontinued due to toxicity. Safety of RA therapies is always a concern because most of these treatments are generally immunosuppressive causing a risk of opportunistic infection or increased serious adverse side effects
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
