Granulocyte death mediated by specific antibodies in intravenous immunoglobulin (IVIG)

Graeter, Stefanie; Simon, Hans‐Uwe; Gunten, Stephan von

doi:10.1016/j.phrs.2019.02.007

Cited by 17 publications

(21 citation statements)

References 70 publications

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“…In vivo studies revealed that IVIg inhibits neutrophil recruitment and activation through the activation of SHP-1 via FcγRIII-mediated mechanisms ( 127 ). Furthermore, IVIg contains anti-Siglec autoantibodies that can regulate neutrophil apoptosis in a dose-dependent cytotoxic manner via F(ab)′ 2 -mediated mechanisms ( 33 , 128 , 129 ). Interestingly, high-dose sulfo-IVIg preparations significantly reduce NET formation in vitro as well as in rat models ( 130 ).…”

Section: The Immunopathological Hypothesis Of Viral Pneumoniamentioning

confidence: 99%

High-Dose Intravenous Immunoglobulins in the Treatment of Severe Acute Viral Pneumonia: The Known Mechanisms and Clinical Effects

Liu

Cao

2020

Front. Immunol.

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The current outbreak of viral pneumonia, caused by novel coronavirus SARS-CoV-2, is the focus of worldwide attention. The WHO declared the COVID-19 outbreak a pandemic event on Mar 12, 2020, and the number of confirmed cases is still on the rise worldwide. While most infected individuals only experience mild symptoms or may even be asymptomatic, some patients rapidly progress to severe acute respiratory failure with substantial mortality, making it imperative to develop an efficient treatment for severe SARS-CoV-2 pneumonia alongside supportive care. So far, the optimal treatment strategy for severe COVID-19 remains unknown. Intravenous immunoglobulin (IVIg) is a blood product pooled from healthy donors with high concentrations of immunoglobulin G (IgG) and has been used in patients with autoimmune and inflammatory diseases for more than 30 years. In this review, we aim to highlight the known mechanisms of immunomodulatory effects of high-dose IVIg therapy, the immunopathological hypothesis of viral pneumonia, and the clinical evidence of IVIg therapy in viral pneumonia. We then make cautious therapeutic inferences about high-dose IVIg therapy in treating severe COVID-19. These inferences may provide relevant and useful insights in order to aid treatment for COVID-19.

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Section: The Immunopathological Hypothesis Of Viral Pneumoniamentioning

confidence: 99%

High-Dose Intravenous Immunoglobulins in the Treatment of Severe Acute Viral Pneumonia: The Known Mechanisms and Clinical Effects

Liu

Cao

2020

Front. Immunol.

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“…However, non-canonical functions of Abs also contribute to the realization of the IVIg effector functions. For instance, many effects of IVIg preparations on granulocytes may be due to receptor agonist activity [ 194 ]. In particular, Abs to tumor necrosis factor receptors contained in IVIg preparations can lead to apoptotic death of granulocytes [ 194 ].…”

Section: Ivig-mediated Effector Functions Are Determined By Canonimentioning

confidence: 99%

“…For instance, many effects of IVIg preparations on granulocytes may be due to receptor agonist activity [ 194 ]. In particular, Abs to tumor necrosis factor receptors contained in IVIg preparations can lead to apoptotic death of granulocytes [ 194 ]. We hypothesize that catalytic Abs present in the serum of some healthy donors may also contribute to the realization of the effects of IVIg preparations.…”

Section: Ivig-mediated Effector Functions Are Determined By Canonimentioning

confidence: 99%

Immunoglobulins with Non-Canonical Functions in Inflammatory and Autoimmune Disease States

Ermakov

Nevinsky

Buneva

2020

IJMS

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Immunoglobulins are known to combine various effector mechanisms of the adaptive and the innate immune system. Classical immunoglobulin functions are associated with antigen recognition and the initiation of innate immune responses. However, in addition to classical functions, antibodies exhibit a variety of non-canonical functions related to the destruction of various pathogens due to catalytic activity and cofactor effects, the action of antibodies as agonists/antagonists of various receptors, the control of bacterial diversity of the intestine, etc. Canonical and non-canonical functions reflect the extreme human antibody repertoire and the variety of antibody types generated in the organism: antigen-specific, natural, polyreactive, broadly neutralizing, homophilic, bispecific and catalytic. The therapeutic effects of intravenous immunoglobulins (IVIg) are associated with both the canonical and non-canonical functions of antibodies. In this review, catalytic antibodies will be considered in more detail, since their formation is associated with inflammatory and autoimmune diseases. We will systematically summarize the diversity of catalytic antibodies in normal and pathological conditions. Translational perspectives of knowledge about natural antibodies for IVIg therapy will be also discussed.

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“…Neutrophil survival is regulated by cell surface receptors, such as FAS, TNF-R1 or Siglec-9 (33,34). Preincubation of IVIG with neutrophils has been shown to diminish the cytotoxicity of IVIG, suggesting a role of specific antibodies to surface receptors contained in IVIG (16).…”

Section: Enhanced Anti-fas Activity Of Fe(ii)-ivig On Neutrophilsmentioning

confidence: 99%

Enhanced Pro-apoptotic Effects of Fe(II)-Modified IVIG on Human Neutrophils

et al. 2020

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Mild modification of intravenous immunoglobulin (IVIG) has been reported to result in enhanced polyspecificity and leveraged therapeutic effects in animal models of inflammation. Here, we observed that IVIG modification by ferrous ions, heme or low pH exposure, shifted the repertoires of specificities in different directions. Ferrous ions exposed Fe(II)-IVIG, but not heme or low pH exposed IVIG, showed increased pro-apoptotic effects on neutrophil granulocytes that relied on a FAS-dependent mechanism. These effects were also observed in human neutrophils primed by inflammatory mediators or rheumatoid arthritis joint fluid in vitro, or patient neutrophils ex vivo from acute Crohn's disease. These observations indicate that IVIG-mediated effects on cells can be enhanced by IVIG modification, yet specific modification conditions may be required to target specific molecular pathways and eventually to enhance the therapeutic potential.

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Granulocyte death mediated by specific antibodies in intravenous immunoglobulin (IVIG)

Cited by 17 publications

References 70 publications

High-Dose Intravenous Immunoglobulins in the Treatment of Severe Acute Viral Pneumonia: The Known Mechanisms and Clinical Effects

High-Dose Intravenous Immunoglobulins in the Treatment of Severe Acute Viral Pneumonia: The Known Mechanisms and Clinical Effects

Immunoglobulins with Non-Canonical Functions in Inflammatory and Autoimmune Disease States

Enhanced Pro-apoptotic Effects of Fe(II)-Modified IVIG on Human Neutrophils

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