Abstract
Immunoglobulin D (IgD) is a surface immunoglobulin that is expressed as either membrane IgD (mIgD) or secreted IgD (sIgD). Researchers have shown that sIgD is often elevated in patients with autoimmune diseases. The possible roles of sIgD on the function of peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA) are still unclear. In this study, we compared the expression of sIgD, mIgD and IgD receptor (IgDR) in RA patients and healthy controls, and investigated the effect of sIgD on the function of PBMCs. We found that the levels of sIgD, mIgD and IgDR were significantly higher in RA patients compared with healthy controls. The concentrations of sIgD were positively correlated with soluble receptor activator of nuclear factor-κB ligand (sRANKL), rheumatoid factor (RF) and C-reactive protein (CRP) in RA patients. Strikingly, IgD could enhance the proliferation of PBMCs and induce IL-1α, IL-1β, TNF-α, IL-6 and IL-10 production from PBMCs. Moreover, the percentage of activated T cell subsets (CD4+CD69+, CD4+CD154+) and activated B cell subsets (CD19+CD23+, CD19+CD21+, CD19+IgD+ and CD19-CD138+) were increased by IgD. The percentage of unactivated T cell subset (CD4+CD62L+) and immature B cell subset (CD19+IgM+IgD-) were decreased by IgD in PBMCs. Furthermore, the expressions of IgDR on T and B cells were significantly increased by treatment with IgD. Our results demonstrate that IgD enhanced the activation of PBMCs, which may contribute to RA pathogenesis. Therefore, IgD could be a potential novel immunotherapeutic target for the management of RA.
Highlights
Immunoglobulin D (IgD) is an immunoglobulin (Ig) isotype that can be expressed as membrane IgD or secreted IgD
Little membrane IgD (mIgD) was detected on total T cells (CD3+) and total helper T cells (CD3+CD4+), which was consistent with the finding of Chen K et al [6]
The results showed the expression of Number of subjects Age Female/male ratio secreted IgD (sIgD) sRANKL rheumatoid factor (RF) (IU/mL) Erythrocytes sedimentation rate (ESR) Anti-CCP (RU/mL) C-reactive protein (CRP)
Summary
Immunoglobulin D (IgD) is an immunoglobulin (Ig) isotype that can be expressed as membrane IgD (mIgD) or secreted IgD (sIgD). As an important marker of B cell development and maturation, mIgD is co-expressed with IgM on more than 90% of mature B cells
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