Abstract
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and T cell hyper-activation. Emerging evidence has shown that the stimulation of immunoglobulin D (IgD) induces T cell activation and may contribute to disease pathogenesis. In this study, the sIgD concentrations were positively associated with disease activity score in 28 joints (DAS28) and anti-cyclic citrullinated peptide (anti-CCP) in RA. We demonstrated that IgD-Fc-Ig (composed of human IgD Fc domain and IgG1 Fc domain, obtained through prokaryotic protein expression and chromatography purification) effectively inhibited the activation and proliferation of T cells in healthy controls and PBMCs in RA patients stimulated by IgD, recovered the Th17/Treg cell subset balance, and downregulated p-Lck and p-ZAP70 expression. Moreover, in vivo, IgD-Fc-Ig decreased the swollen joint counts and arthritis indices in mice with collagen-induced arthritis (CIA), and ameliorated histopathological changes in joint and spleen tissue. It also downregulated thymocyte proliferation and reduced the percentage of helper T cells (Th) and CD154+ T cells, reversed the imbalance of Th1/Th2 and Th17/Treg cell subsets, reduced cytokine and chemokine levels, and inhibited p-Lck and p-ZAP70 expression. Our data suggest that IgD-Fc-Ig fusion protein regulates T cell activity in RA. These findings have potential implications for IgD-targeted strategies to treat IgD-associated RA.
Highlights
Rheumatoid arthritis (RA) is the most common chronic autoimmune disease and induces mobility restriction, which is characterized by chronic inflammation, synovium hyperplasia, joint destruction, and T cell hyper-activation [1]
RA patients had higher levels of secreted IgD (sIgD) (98.55 ± 5.107 μg/mL) in their plasma compared to healthy controls (4.832 ± 0.3298 μg/mL) (P < 0.0001) (Figure 1A)
Our data indicated that sIgD levels were closely associated with severity of RA
Summary
Rheumatoid arthritis (RA) is the most common chronic autoimmune disease and induces mobility restriction, which is characterized by chronic inflammation, synovium hyperplasia, joint destruction, and T cell hyper-activation [1]. Newly emerging treatments targeting inflammatory cytokines, such as TNF-α production co-stimulated by B cells and T-cell co-stimulation, have been used to treat RA; many patients do not respond well to this therapy [8]. This treatment may cause serious adverse reactions including immunosuppression, leading to increased risk of infections
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