Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNFα-dependent and Fc-receptor–independent way

Jarius, Sven; Eichhorn, Peter; Albert, Michael H.; Wagenpfeil, Stefan; Wick, Manfred; Belohradsky, Bernd H.; Hohlfeld, Reinhard; Jenne, Dieter E.; Voltz, Raymond

doi:10.1182/blood-2005-12-019604

Cited by 50 publications

(31 citation statements)

References 61 publications

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“…Spontaneous NET formation from ex vivo-isolated PMNs physiologically depends on the inflammatory microenvironment in which granulocytes are generated. Indeed, granulocytes obtained from agar plugs subcutaneously implanted into TNF-KO and IFN␥-KO mice were unable of NETosis (supplemental Figure 4) in line with in vitro data showing that TNF can directly activate neutrophils 21 and that IFNs act as priming factors on mature neutrophils for NET formation. 22 Notably, both IFN␥-KO and TNF-KO mice did not show defective PMN recruitment.…”

supporting

confidence: 62%

Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity

Sangaletti

Tripodo

Chiodoni

et al. 2012

Blood

351

314

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Antineutrophil cytoplasmic antibodies (ANCAs) target proteins normally retained within neutrophils, indicating that cell death is involved in the autoimmunity process. Still, ANCA pathogenesis remains obscure. ANCAs activate neutrophils inducing their respiratory burst and a peculiar form of cell death, named NETosis, characterized by formation of neutrophil extracellular traps (NETs), decondensed chromatin threads decorated with cytoplasmic proteins endorsed with antimicrobial activity. NETs have been consistently detected in ANCA-associated small-vessel vasculitis, and this association prompted us to test whether the peculiar structure of NET favors neutrophil proteins uploading into myeloid dendritic cells and the induction of ANCAs and associated autoimmunity. Here we show that myeloid DCs uploaded with and activated by NET components induce ANCA and autoimmunity when injected into naive mice. DC uploading and autoimmunity induction are prevented by NET treatment with DNAse, indicating that NET structural integrity is needed to maintain the antigenicity of cytoplasmic proteins. We found NET intermingling with myeloid dendritic cells also positive for neutrophil myeloperoxidase in myeloperoxidase-ANCA-associated microscopic poliangiitis providing a potential correlative picture in human pathology. These data provide the first demonstration that NET structures are highly immunogenic such to trigger adaptive immune response relevant for autoimmunity.

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supporting

confidence: 62%

Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity

Sangaletti

Tripodo

Chiodoni

et al. 2012

Blood

351

314

View full text Add to dashboard Cite

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“…Except for thyroiditis, autopsy with histologic, biochemical, and toxicologic analyses did not reveal any underlying disease. 3 In October 2007, a 19-year-old female student from Austria died 3 weeks after vaccination with Gardasil. The Austrian Federal Agency for Safety in Public Health denied any causal link between the vaccination and the death of the teenager.…”

Section: Viral Vaccines For Dermatologic Disease: Some Additional Infmentioning

confidence: 99%

“…Studies on various batches of immunoglobulin had found atypical antineutrophil cytoplasmic antibodies, and these antibodies were shown to have the capacity of inducing oxidativeburst reaction. 3 Autoantibodies against liver antigens were demonstrated with seven IVIG preparations, and preparations that involved a fractionation step at low pH correlated with increased IgG autoreactivity. 2 It is also important to note that pathogen-specific antibodies are present in IVIG preparations in widely varying amounts.…”

mentioning

confidence: 98%

Both autoantibodies and pathogen-specific antibodies are present in immunoglobulin preparations and reflect characteristics of the donor population

Khan¹,

Sims²,

Raine³

et al. 2008

Journal of the American Academy of Dermatology

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“…Tam et al [11] reported a child with Guillain-Barre syndrome, in whom the authors revealed the presence of antineutrophil antibodies. Some authors suggested roles of atypical antineutrophil cytoplasmic antibodies (ANCA) [12,13]. IgG aggregates with immune-complex-like activity was suggested as the cause of transient neutropenia by some researchers [9,14].…”

Section: Discussionmentioning

confidence: 99%

Neutropenia Following Intravenous Immunoglobulin Administration in a Patient with Multifocal Motor Neuropathy with Conduction Block

Sohn¹,

Kim²

2017

J Neurol Neurophysiol

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Intravenous immunoglobulin (IVIG) is the treatment of choice in patients with multifocal motor neuropathy with conduction block (MMNCB). Although IVIG is considered generally safe, neutropenia following IVIG infusion has been recognized as a rare hematologic side effect. Herein we report a patient with MMNCB who developed severe neutropenia following IVIG administration.A 41 year old woman presented with progressive weakness of her left lower extremity with frequent muscle cramps. Nerve conduction study revealed marked conduction blocks on right ulnar and right tibial nerves. Serum IgM anti-GM1 antibody was detected. Neutrophil count decreased from day 2 and recovered after 2 weeks following IVIG infusion. To our knowledge, neutropenia following IVIG infusion in MMNCB has never been discussed apart, although it can be an important clinical issue especially for patients with MMNCB.

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Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNFα-dependent and Fc-receptor–independent way

Cited by 50 publications

References 61 publications

Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity

Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity

Both autoantibodies and pathogen-specific antibodies are present in immunoglobulin preparations and reflect characteristics of the donor population

Neutropenia Following Intravenous Immunoglobulin Administration in a Patient with Multifocal Motor Neuropathy with Conduction Block

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