Antibody-mediated catalysis: Induction and therapeutic relevance

Mahendra, Ankit; Sharma, Meenu; Rao, Desirazu N.; Peyron, Ivan; Planchais, Cyril; Dimitrov, Jordan D.; Kaveri, Srini V.; Lacroix‐Desmazes, Sébastien

doi:10.1016/j.autrev.2012.10.009

Cited by 23 publications

(29 citation statements)

References 58 publications

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“…For example, DNAhydrolyzing autoantibodies have been detected in the sera of patients with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, or HIV infection (30,31). Moreover, abzymes against coagulation factors, such as factor VIII, have been reported in patients with hemophilia A (32), which may interfere with hemostasis under pathological conditions (33). In this study, we found several Plg cross-reactive anti-NS1 mAbs generated from DENV NS1-immunized mice with enzymatic activity that were able to directly convert Plg to Plm.…”

Section: Discussionmentioning

confidence: 99%

Dengue Virus Nonstructural Protein 1–Induced Antibodies Cross-React with Human Plasminogen and Enhance Its Activation

Chuang

Lin

et al. 2016

The Journal of Immunology

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Dengue virus (DENV) infection is the most common mosquito-borne viral disease, and it can cause life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Abnormal activation of the coagulation and fibrinolysis system is one of the hallmarks of DHF/DSS. However, the mechanism underlying hemorrhage in DHF/DSS remains elusive. In previous studies, plasminogen (Plg) cross-reactive Abs, which can recognize DENV nonstructural protein (NS) 1, have been found in dengue patients. However, it is unclear whether these Abs are indeed induced by DENV NS1. Thus, we immunized mice with recombinant NS1 from both bacteria and drosophila to determine whether NS1 can induce Plg cross-reactive Abs. The results from the NS1-immunized mouse sera indicated that NS1 immunization induced Abs that could cross-react with Plg. To study the effects of these NS1-induced Plg cross-reactive Abs on fibrinolysis, we isolated several Plg cross-reactive anti-NS1 mAbs from these mice and found that some of them could enhance Plg activation. In addition, epitope mapping with a phage-displayed random peptide library revealed that one of these mAbs (2A5) could recognize NS1 C-terminal residues 305–311, which share sequence homology with Plg residues 590–597. A synthetic peptide of NS1 residues 305–311 could inhibit the binding of both 2A5 and its Fab to Plg and its enhanced activation. Thus, our results suggest that DENV NS1 can induce Plg cross-reactive Abs through molecular mimicry, which can enhance Plg activation and may contribute to the pathogenesis of DHF/DSS.

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Section: Discussionmentioning

confidence: 99%

Dengue Virus Nonstructural Protein 1–Induced Antibodies Cross-React with Human Plasminogen and Enhance Its Activation

Chuang

Lin

et al. 2016

The Journal of Immunology

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“…Although abzymes can be both protective (e.g. secretory sIgA abzymes hydrolysing HIV gp120) [21] or deleterious (hydrolysing myelin basic protein) [22], or even combining two distinct activities [23], growing evidence suggests important functional roles for catalytic antibodies in homeostasis, autoimmune disease and protection against infection [21,22,24]. One should also keep in mind the multifarious roles of sialic acids in immunity [25], probably causing abzymes with sialidase activity to influence a plethora of functions.…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Desialylation of dying cells with catalytically active antibodies possessing sialidase activity facilitate their clearance by human macrophages

Tomin

Dumych

Tolstyak

et al. 2014

Clinical and Experimental Immunology

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OTHER ARTICLES PUBLISHED IN THIS SERIES Dying autologous cells as instructors of the immune system. Clinical and Experimental Immunology 2015, 179: 1-4. Anti-dsDNA antibodies as a classification criterion and a diagnostic marker for systemic lupus erythematosus: critical remarks. Clinical and Experimental Immunology 2015, 179: 5-10. The effect of cell death in the initiation of lupus nephritis. Clinical and Experimental Immunology 2015, 179: 11-16 SummaryRecently we reported the first known incidence of antibodies possessing catalytic sialidase activity (sialidase abzymes) in the serum of patients with multiple myeloma and systemic lupus erythematosus (SLE). These antibodies desialylate biomolecules, such as glycoproteins, gangliosides and red blood cells. Desialylation of dying cells was demonstrated to facilitate apoptotic cell clearance. In this study we assessed the possibility to facilitate dying cell clearance with the use of F(ab)2 fragments of sialidase abzymes. Two sources of sialidase abzymes were used: (i) those isolated from sera of patients with SLE after preliminary screening of a cohort of patients for sialidase activity; and (ii) by creating an induced sialidase abzyme through immunization of a rabbit with synthetic hapten consisting of a non-hydrolysable analogue of sialidase reaction conjugated with bovine serum albumin (BSA) or keyhole limpet haemocyanin (KLH). Antibodies were purified by ammonium sulphate precipitation, protein-G affinity chromatography and size exclusion-high performance liquid chromatography (HPLC-SEC). Effect of desialylation on efferocytosis was studied using human polymorphonuclear leucocytes (PMN), both viable and aged, as prey, and human monocyte-derived macrophages (MoMa). Treatment of apoptotic and viable prey with both disease-associated (purified from blood serum of SLE patients) and immunization-induced (obtained by immunization of rabbits) sialidase abzymes, its F(ab)2 fragment and bacterial neuraminidase (as positive control) have significantly enhanced the clearance of prey by macrophages. We conclude that sialidase abzyme can serve as a protective agent in autoimmune patients and that artificial abzymes may be of potential therapeutic value.

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“…These catalytic Abs can occur naturally and ubiquitously in healthy individuals, but are preferentially found in the Ig repertoire of individuals with autoimmune disease. Their pathogenic or beneficial role still remains unclear [8,9].…”

Section: Reviewmentioning

confidence: 98%

Antibodies as a source of anti-infective peptides: an update

Magliani

Giovati

Ciociola

et al. 2015

Future Microbiology

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This review focuses on antibodies (Abs) and their function in immune protection, with particular emphasis on microbicidal Abs. Some aspects of Abs and Ab-drug conjugates as targeting therapeutic agents are also discussed. The main aim, however, is devoted to Ab-derived peptides modulating functions of the immune system and to the latest experimental evidence of Abs as a source of anti-infective and antitumor peptides derived from their complementarity determining regions and constant regions.

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Antibody-mediated catalysis: Induction and therapeutic relevance

Cited by 23 publications

References 58 publications

Dengue Virus Nonstructural Protein 1–Induced Antibodies Cross-React with Human Plasminogen and Enhance Its Activation

Dengue Virus Nonstructural Protein 1–Induced Antibodies Cross-React with Human Plasminogen and Enhance Its Activation

Desialylation of dying cells with catalytically active antibodies possessing sialidase activity facilitate their clearance by human macrophages

Antibodies as a source of anti-infective peptides: an update

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