B cells participate in the induction and maintenance of systemic autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, via production of pathogenic autoantibodies, ...contributing to the formation of immune complexes. Immune complex deposition in the kidney and joints causes inflammation and organ destruction, and chemokine production enhances T cell activation and tissue damage. The development of the disorder depends on several factors, for example, genetic susceptibility, environmental factors or immune dysregulation. Traditional therapies, which aimed at the alleviation of symptoms, are giving way to biological therapies with the potential of disrupting disease progression. This article focuses on antibody therapies, especially on the applications of single-chain antibodies, as new biological agents for the treatment of systemic autoimmune disorders.
Clarifies the mechanism of immune complex-mediated inflammation and modulation of collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA), and specifically the roles played by ...antibodies specific for bovine type II collagen (CII) and Fcγ receptors. Source: National Library of New Zealand Te Puna Matauranga o Aotearoa, licensed by the Department of Internal Affairs for re-use under the Creative Commons Attribution 3.0 New Zealand Licence.
Immune complexes (ICs) induce effective pathogen-specific innate and humoral immune response via immunecomplex-binding receptors, such as murine complement receptor type 1 and 2 (mCR1/2) and murine ...low-affinity Fc receptors for IgG (mFcgammaRII and III). The exact function of mCR1/2 in cooperation with mFcgammaRII/III in modulation of humoral immunity has not yet been adequately clarified. The aim of this study was to target these receptors by specific single-chain fragments of antibody (scFv), either individually or in combination, thus modelling the action of IC. For targeting, we used scFv derived from the well-characterized 7g6 and 2.4g2 monoclonal antibodies recognizing mCR1/2 and mFcgammaRII/III, respectively. These scFvs were monobiotinylated and conjugated to streptavidin or streptavidin-coated microspheres. Such complexes were investigated with respect to target receptor recognition and in vivo localization. Antibody response against the constructs was measured by ELISA and ELISPOT. Results show that targeting streptavidin complexes to mFcgammaRII/III induces stronger IgG1 response than targeting to mCR1/2 yet both strategies enhance the antibody response compared to the control group immunized with non-targeted peptide-streptavidin complexes. Moreover, the immunogenicity of coupled antigens increased using microspheres as carrier, instead of using soluble streptavidin. In summery, our in vivo experiments reveal that mFcgammaRII/III is more potent a target than CR1/2 and show that combined targeting of CR1/2 and FcgammaRII/III receptors does not result in cumulative enhancement of the antigen specific immune response. In addition, microparticle-mediated enhancement of immunization can be further improved by FcgammaRII/III targeting.
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