Multimerized IgG1 Fc molecule as an anti-inflammatory agent

Stephen-Victor, Emmanuel; Bayry, Jagadeesh

doi:10.1038/s41584-018-0013-9

Cited by 7 publications

(11 citation statements)

References 10 publications

(16 reference statements)

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“…In summary, IVIG can interfere at all steps of immune response from the early initiation phase to the later effector phase that leads to clinical disease ( Figure. [97][98][99][100][101][102], a single mechanism might not account for its therapeutic benefit in autoimmune diseases [42,65,103].…”

Section: Natural Igg (Nigg): Role Of Nabs In Immune Tolerance/homeostmentioning

confidence: 99%

Natural Antibodies: from First-Line Defense Against Pathogens to Perpetual Immune Homeostasis

Maddur

Lacroix‐Desmazes

Dimitrov

et al. 2019

Clinic Rev Allerg Immunol

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Section: Natural Igg (Nigg): Role Of Nabs In Immune Tolerance/homeostmentioning

confidence: 99%

Natural Antibodies: from First-Line Defense Against Pathogens to Perpetual Immune Homeostasis

Maddur

Lacroix‐Desmazes

Dimitrov

et al. 2019

Clinic Rev Allerg Immunol

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“…Although monoclonal antibodies (MAbs) and recombinant proteins have revolutionized the management of autoimmune diseases, and several other novel immunotherapies are in pipeline, [9][10][11][12][13][14][15][16][17][18] immunotherapy with IVIG is still attractive and has several advantages because of broad-spectrum action and safety profiles. These mechanisms of IVIG represent functions of circulating normal IgG in the regulation of immune tolerance and immune homeostasis.…”

Section: Discussionmentioning

confidence: 99%

Intravenous immunoglobulin suppresses the polarization of both classically and alternatively activated macrophages

Saha

Kothapalli

Patil

et al. 2019

Human Vaccines & Immunotherapeutics

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Intravenous immunoglobulin (IVIG) is one of the widely used immunotherapeutic molecules in the therapy of autoimmune and inflammatory diseases. Previous reports demonstrate that one of the antiinflammatory actions of IVIG implicates suppression of macrophage activation and release of their inflammatory mediators. However, macrophages are highly plastic and depending on the microenvironmental signals, macrophages can be polarized into pro-inflammatory classic (M1) or anti-inflammatory alternative (M2) type. This plasticity of macrophages raised additional questions on the role of IVIG towards macrophage polarization. In the present report, we show that IVIG affects the polarization of both classically and alternatively activated macrophages and this process is F(ab') 2-independent. Our data thus indicate the lack of reciprocal regulation of inflammatory and non-inflammatory macrophages by IVIG.

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“…Nonetheless, the clinical successes of eculizumab portends both the scientific utility of such inhibitors in understanding the precise etiology of diseases in which complement is implicated and the potential value of exploring other suppression strategies. To this end, additional strategies to suppress complement activity include a small‐molecule C5 inhibitor, 39 a single‐chain antibody linked to a complement inhibitor, 40 small interfering RNA against C5, 41 inhibitory anti‐C1s mAb, 42 C3 inhibition, 43 a variety of (IVIG)‐mimetic IgG1–Fc multimers 44‐47 and disruption of IC by relatively complement‐inert subclasses such as human IgG4 48 . Beyond canonical complement regulatory factors, a role for a histological biomarker in Alzheimer’s disease and atherosclerosis, apolipoprotein E, in attenuation of unresolvable inflammatory diseases was recently identified.…”

Section: Classical Complement Pathologies and Interventionsmentioning

confidence: 99%

Antibody‐mediated complement activation in pathology and protection

Goldberg

Ackerman

2020

Immunol Cell Biol

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Antibody-dependent complement activity is associated not only with autoimmune morbidity, but also with antitumor efficacy. In infectious disease, both recombinant monoclonal antibodies and polyclonal antibodies generated in natural adaptive responses can mediate complement activity to protective, therapeutic or disease-enhancing effect. Recent advances have contributed to the structural resolution of molecular complexes involved in antibody-mediated complement activation, defining the avid nature of participating interactions and pointing to how antibody isotype, subclass, hinge flexibility, glycosylation state, amino acid sequence and the contextual nature of the cognate antigen/ epitope are all factors that can determine complement activity through impact on antibody multimerization and subsequent recruitment of complement component 1q. Beyond the efficiency of activation, complement activation products interact with various cell types that mediate immune adherence, trafficking, immune education and innate functions. Similarly, depending on the anatomical location and extent of activation, complement can support homeostatic restoration or be leveraged by pathogens or neoplasms to enhance infection or promote tumorigenic microenvironments, respectively. Advances in means to suppress complement activation by intravenous immunoglobulin (IVIG), IVIG mimetics and complement-intervening antibodies represent proven and promising exploratory therapeutic strategies, while antibody engineering has likewise offered frameworks to enhance, eliminate or isolate complement activation to interrogate in vivo mechanisms of action. Such strategies promise to support the optimization of antibody-based drugs that are able to tackle emerging and difficult-to-treat diseases by improving our understanding of the synergistic and antagonistic relationships between antibody mechanisms mediated by Fc receptors, direct binding and the products of complement activation.

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Multimerized IgG1 Fc molecule as an anti-inflammatory agent

Cited by 7 publications

References 10 publications

Natural Antibodies: from First-Line Defense Against Pathogens to Perpetual Immune Homeostasis

Natural Antibodies: from First-Line Defense Against Pathogens to Perpetual Immune Homeostasis

Intravenous immunoglobulin suppresses the polarization of both classically and alternatively activated macrophages

Antibody‐mediated complement activation in pathology and protection

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