Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting

Pathological antibodies have been demonstrated to play a key role in type II immune hypersensitivity reactions, resulting in the destruction of healthy tissues and leading to considerable morbidity for the patient. Unfortunately, current treatments present significant iatrogenic risk while still falling short for many patients in achieving clinical remission. In the present work, we explored the capability of target cell membrane-coated nanoparticles to abrogate the effect of pathological antibodies in an effort to minimize disease burden, without the need for drug-based immune suppression. Inspired by antibody-driven pathology, we used intact RBC membranes stabilized by biodegradable polymeric nanoparticle cores to serve as an alternative target for pathological antibodies in an antibody-induced anemia disease model. Through both in vitro and in vivo studies, we demonstrated efficacy of RBC membrane-cloaked nanoparticles to bind and neutralize anti-RBC polyclonal IgG effectively, and thus preserve circulating RBCs.

https://www.pnas.org/content/pnas/111/37/13481.full.pdf

Clearance of pathological antibodies using biomimetic nanoparticles.

Autoimmune hemolytic anemia (AIHA) is caused by the increased destruction of red blood cells (RBCs) by anti-RBC autoantibodies with or without complement activation. RBC destruction may occur both by a direct lysis through the sequential activation of the final components of the complement cascade (membrane attack complex), or by antibody-dependent cell-mediated cytotoxicity (ADCC). The pathogenic role of autoantibodies depends on their class (the most frequent are IgG and IgM), subclass, thermal amplitude (warm and cold forms),as well as affinity and efficiency in activating complement. Several cytokines and cytotoxic mechanisms (CD8+ T and natural killer cells) are further involved in RBC destruction. Moreover, activated macrophages carrying Fc receptors may recognize and phagocyte erythrocytes opsonized by autoantibodies and complement. Direct complement-mediated lysis takes place mainly in the circulations and liver, whereas ADCC, cytotoxicity, and phagocytosis occur preferentially in the spleen and lymphoid organs. The degree of intravascular hemolysis is 10-fold greater than extravascular one. Finally, the efficacy of the erythroblastic compensatory response can greatly influence the clinical picture of AIHA. The interplay and relative burden of all these pathogenic mechanisms give reason for the great clinical heterogeneity of AIHAs, from fully compensated to rapidly evolving fatal cases.

/pdf/new-insights-in-the-pathogenesis-of-autoimmune-hemolytic-5e1r8jb41u.pdf

New Insights in the Pathogenesis of Autoimmune Hemolytic Anemia.

Efficacy and safety of rituximab in auto-immune hemolytic anemia: A meta-analysis of 21 studies

https://minerva-access.unimelb.edu.au/bitstream/handle/11343/250305/PMC6269125.pdf

Associations Between Non-neurological Autoimmune Disorders and Psychosis: A Meta-analysis

Diagnosis and classification of autoimmune hemolytic anemia.

Degradable, Photochemically Printable Poly(propylene fumarate)-Based ABA Triblock Elastomers.

Synthetic design and investigation of novel polymeric surfactants

Alternative polymer feedstocks are highly desirable to address environmental, social, and security concerns associated with petrochemical-based materials. Lignocellulosic biomass (LCB) has emerged as one critical feedstock in this regard because it is an abundant and ubiquitous renewable resource, which can be deconstructed to generate valuable fuels, chemicals, and small molecules/oligomers that are amenable to modification and polymerization. However, the diversity of LCB complicates the evaluation of biorefinery concepts in areas including process scale-up, production outputs, plant economics, and life-cycle management. We discuss aspects of current LCB biorefinery research with a focus on the major process stages, including feedstock selection, fractionation/deconstruction, and characterization, along with product purification, functionalization, and polymerization to manufacture valuable macromolecular materials. We highlight opportunities to valorize underutilized and complex feedstocks, leverage advanced characterization techniques to predict and manage biorefinery outputs, and increase the fraction of biomass converted into valuable products. Expected final online publication date for the Annual Review of Chemical and Biomolecular Engineering, Volume 14 is June 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Garrett F. Bass

Papers

Diagnosis and classification of autoimmune hemolytic anemia.

Degradable, Photochemically Printable Poly(propylene fumarate)-Based ABA Triblock Elastomers.

Synthetic design and investigation of novel polymeric surfactants

Engineering Innovations, Challenges, and Opportunities for Lignocellulosic Biorefineries: Leveraging Biobased Polymer Production.