Intravenous immunoglobulins neutralize blocking antibodies in Guillain‐Barré syndrome

Buchwald, B.; Ahangari, Raheleh; Weishaupt, Andreas; Toyka, Klaus V.

doi:10.1002/ana.10205

Cited by 132 publications

(85 citation statements)

References 45 publications

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“…Plasmapheresis and IVIG are the main therapies for AIDP. Plasmapheresis removes circulating autoantibodies in the blood, while IVIG may neutralize autoantibodies (13) and prevent complement-mediated nerve damage (14).…”

Section: Discussionmentioning

confidence: 99%

Recurrent Acute Inflammatory Demyelinating Polyradiculoneuropathy Following R-Chop Treatment for Non-Hodgkin Lymphoma

Liang

Singh²,

Witzig³

2013

Baylor University Medical Center Proceedings

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Proc (Bayl Univ Med Cent) 2013;26(2):156-158Acute flaccid paralysis following chemotherapy has a wide differential diagnosis, including drug toxicity, acute inflammatory demyelinating polyradiculoneuropathy (AIDP), and malignant nerve infiltration. We present a case of recurrent acute quadriparesis due to AIDP following chemotherapy for non-Hodgkin lymphoma, which resolved each time following administration of intravenous immunoglobulin. Although many chemotherapeutic agents can cause neurologic side effects, such as peripheral neuropathy, drug toxicity as a cause is a diagnosis of exclusion.A cute fl accid paralysis following chemotherapy has a wide diff erential diagnosis, including drug toxicity, acute infl ammatory demyelinating polyradiculoneuropathy (AIDP), and malignant nerve infi ltration. We present a case of recurrent acute quadriparesis due to AIDP following chemotherapy for non-Hodgkin lymphoma, which resolved each time following administration of intravenous immunoglobulin (IVIG). CASE PRESENTATIONA 62-year-old man with recently diagnosed stage IV diffuse large B-cell lymphoma presented for his fi rst cycle of chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Th e diagnosis had been confi rmed by pleural and testicular biopsies. Pretreatment positron emission tomography (PET) scan had revealed diff use nodal activity and extranodal involvement in the pleura, testicles, and bones (Figure 1a). Th e patient had been otherwise healthy.He tolerated his fi rst cycle of R-CHOP chemotherapy with no issues. Two days after completing the R-CHOP cycle, he began to notice bilateral lower-extremity weakness, which began at his feet and gradually moved upwards to his hip girdle muscles. Th e weakness gradually worsened to the point where he needed to use his hands to push off and stand from a seated position. Shortly thereafter, he noted bilateral arm weakness and became unable to stand due to the inability to push off with his arms. He also developed numbness in all four extremities from his mid forearms distally and the knees down. Th roughout this time, he retained bowel and bladder function. His severe weakness and

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Section: Discussionmentioning

confidence: 99%

Recurrent Acute Inflammatory Demyelinating Polyradiculoneuropathy Following R-Chop Treatment for Non-Hodgkin Lymphoma

Liang

Singh²,

Witzig³

2013

Baylor University Medical Center Proceedings

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“…Since functional autoantibodies in other autoimmune diseases including primary Sjögren's syndrome, type 1 diabetes and Guillian-Barre syndrome are neutralized by antiidiotypic antibodies present in IVIg (Buchwald et al, 2002;Cavill et al, 2003;Wan et al, 2008), we investigated whether IVIg exerted a protective effect on narcoleptic IgGmediated CMMC dysfunction. Preincubation of IVIg with narcoleptic IgG neutralized the CMMC disruption, and the functional activity of patient IgG was reduced by passage over Sepharose-bound F(abЈ) 2 derived from IVIg, findings consistent with the presence of a population of antiidiotypic antibodies in IVIg that neutralize the functional autoantibody.…”

Section: Discussionmentioning

confidence: 99%

“…IVIg has proven useful in ameliorating the activity of functional autoantibodies against a number of neuronal targets (Buchwald et al, 2002;Cavill et al, 2003). To evaluate the effect of IVIg on narcoleptic IgG activity in the colon CMMC assay, 20 mg of patient IgG was mixed with an equimolar amount of IVIg or a BSA control.…”

Section: Disruption Of Colonic Cmmc Activity By Narcoleptic Igg Is Nementioning

confidence: 99%

“…IVIg has been proposed to neutralize functional autoantibodies via the presence of antiidiotypic antibodies (Buchwald et al, 2002;Cavill et al, 2003). If IVIg contains antibodies that neutralize the functional autoantibody in narcolepsy IgG, it should be possible to reduce autoantibody activity by passage of patient IgG over a F(abЈ) 2 column derived from IVIg.…”

Section: The Functional Activity Of Narcoleptic Igg Is Neutralized Bymentioning

confidence: 99%

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An Autoantibody in Narcolepsy Disrupts Colonic Migrating Motor Complexes

Jackson¹,

Reed²,

Smith³

et al. 2008

J. Neurosci.

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Despite strong circumstantial evidence for the autoimmune hypothesis of narcolepsy, conventional immunological methods have failed to detect an autoantibody. This study investigated the real-time effects of narcoleptic immunoglobulins on a spontaneous colonic migrating motor complex (CMMC) preparation. IgG from patients with narcolepsy with cataplexy or healthy controls was added directly to isolated mouse colons undergoing CMMC activity to test for autoantibodies that disrupt colonic motility. The effect of immunoglobulins prepared for clinical intravenous treatment (IVIg) on autoantibody-mediated colonic disruption was also assessed. Narcoleptic IgGs markedly reduced the frequency of CMMCs or irreversibly abolished them. Abrogation of CMMCs was followed by an increase in the resting tension of the colon preparation and appearance of atropine-sensitive phasic smooth muscle contractions. IVIg partially neutralized the inhibitory effect of narcoleptic IgG on the CMMCs. The dramatic effect of narcoleptic IgG on CMMC generation is consistent with an autoantibody-mediated disruption of enteric neural pathways. The ex vivo whole-organ approach allows real-time examination of the physiological effects of the narcoleptic autoantibody and offers a new avenue for exploring the autoimmune basis of narcolepsy. The neutralizing effect of IVIg on the autoantibody provides a rationale for the reported clinical improvement in cataplexy when IVIg are given at disease onset.

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“…Additional specificities found in IVIG and implicated as potentially important therapeutic targets are anti-idiotype antibodies that might neutralize pathogenic antibodies such as glycolipid-specific antibodies in GBS or acetylcholine receptor-targeting antibodies in patients with MG [14][15][16][17]. Moreover, the presence of antibodies against T-cell receptors within IVIG preparations might shape the T-cell repertoire during inflammatory responses [18].…”

Section: -Mediated Mechanismsmentioning

confidence: 99%

Efficacy of Intravenous Immunoglobulin in Neurological Diseases

2016

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Owing to its anti-inflammatory efficacy in various autoimmune disease conditions, intravenous immunoglobulin (IVIG)-pooled IgG obtained from the plasma of several thousands individuals-has been used for nearly three decades and is proving to be efficient in a growing number of neurological diseases. IVIG therapy has been firmly established for the treatment of Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy, either as first-line therapy or adjunctive treatment. IVIG is also recommended as rescue therapy in patients with worsening myasthenia gravis and is beneficial as a second-line therapy for dermatomyositis and stiff-person syndrome. Subcutaneous rather than intravenous administration of IgG is gaining momentum because of its effectiveness in patients with primary immunodeficiency and the ease with which it can be administered independently from hospital-based infusions. The demand for IVIG therapy is growing, resulting in rising costs and supply shortages. Strategies to replace IVIG with recombinant products have been developed based on proposed mechanisms that confer the anti-inflammatory activity of IVIG, but their efficacy has not been tested in clinical trials. This review covers new developments in the immunobiology and clinical applications of IVIG in neurological diseases.

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Intravenous immunoglobulins neutralize blocking antibodies in Guillain‐Barré syndrome

Cited by 132 publications

References 45 publications

Recurrent Acute Inflammatory Demyelinating Polyradiculoneuropathy Following R-Chop Treatment for Non-Hodgkin Lymphoma

Recurrent Acute Inflammatory Demyelinating Polyradiculoneuropathy Following R-Chop Treatment for Non-Hodgkin Lymphoma

An Autoantibody in Narcolepsy Disrupts Colonic Migrating Motor Complexes

Efficacy of Intravenous Immunoglobulin in Neurological Diseases

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