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Diminutive decoys: Membrane-cloaked nanoparticles disrupt antibody-mediated autoimmune diseases

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Posted September 20, 2014
Schematic representation of RBC-ANS neutralizing anti-RBC antibodies

Schematic representation of RBC-ANS neutralizing anti-RBC antibodies (anti-RBCs). (A) Anti-RBCs opsonize RBCs for extravascular hemolysis, via phagocytosis, as observed in AIHA and DIA. (B) RBC-ANS absorbs and neutralizes anti-RBCs, thereby protecting RBCs from phagocytosis. Credit: Copp JA, et al. (2014) Clearance of pathological antibodies using biomimetic nanoparticles. Proc Natl Acad Sci USA 111(37): 13481-13486.

What do rheumatoid arthritis, type I diabetes, myasthenia gravis, multiple sclerosis, rheumatic heart disease, and narcolepsy have in common? All of these (and many other) apparently unrelated disorders are caused by autoimmunity, in which the immune system produces antibodies that attack normal, healthy cells and tissues. Currently considered incurable, these autoimmune diseases can be managed – albeit with varying efficacy and sometimes serious side effects – by immunosuppressive (reducing the activation or efficacy of the immune system), anti-inflammatory (steroids), or palliative (for example, insulin injections if type 1 diabetes) treatment. Moreover, autoimmune diseases include a wide range of dysfunctional immune responses known as type II, type III, and type IV immune hypersensitivity reactions.

Recently, scientists at University of California, San Diego demonstrated a novel pathophysiologically-inspired nanoengineering approach to the management of type II hypersensitivity reactions in which antibodies produced by the immune response bind to intrinsic or extrinsic antigens on the surfaces of healthy cells, such as a potentially fatal reaction to penicillin. (Antigens, typically microorganisms and chemicals, provoke an immune response and, if foreign or toxic, bind to a specific antibody.) The researchers demonstrated in a murine model of antibody-induced anemia that by successfully acting as alternative targets for anti-RBC antibodies, polymeric nanoparticles coated with intact red blood cell (RBC) membranes – which the scientists term RBC antibody nanosponges (ANS) – counteracted the effect of pathological antibodies without requiring pharmaceutical immune suppression and thereby protected circulating healthy RBCs. The nanosponges reduced antibody binding to healthy RBCs by up to 95% in a test tube study, and mice injected with anemia-inducing antibodies followed by injection with the nanosponges showed improvements in anemia-related parameters compared with mice injected with antibodies and nanoparticles not coated with an RBC membrane.

Source: Medical Xpress

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