Understanding the Mechanism of Action of Intravenous Immunoglobulins: A Ten Years Experience in Treating Guillain Barré Syndrome

Abstract

Guillain Barré syndrome is an acute immune-mediated, heterogeneous disease that affects the peripheral nervous system and is characterized by rapidly progressive motor deficit, diminished reflexes, cranial nerve involvement, respiratory failure, sometimes with involvement of autonomic nervous system which contribute to the mortality rate. Both T-cells and B-cells are involved in its pathogenesis, finally leading to myelin destruction or axonal damage. The present paper underlines the effect of intravenous immunoglobulins in treating this disease by discussing the pathophysiology of Guillain Barré syndrome with the participation of immune system and the mechanism of action of intravenous immunoglobulins with the reduction of autoantibodies, down regulation of macrophage activity, reduction of inflammatory cytokine levels and cell adhesion molecules thus limiting the self-harm and the passage of autoimmune cells through the blood-nerve barrier. RezumatSindromul Guillain Barré este o boală heterogenă, imun-mediată care afectează sistemul nervos periferic și se caracterizează prin deficit motor rapid progresiv, reflexe osteotendinoase diminuate, afectare de nervi cranieni, uneori cu insuficiență respiratorie și afectare de sistem nervos autonom care contribuie la creșterea ratei de mortalitate. Atât limfocitele T cât și limfocitele B sunt implicate în patogeneză conducând în cele din urmă la distrucția mielinei sau la afectare axonală. Lucrarea de față subliniază rolul imunoglobulinelor intravenoase în tratamentul acestei boli, prezentând fiziopatologia sindromului Guillain Barré, care implică participarea sistemului imun și mecanismul de acțiune al imunoglobulinelor administrate intravenos, care au rol în reducerea titrului de autoanticorpi, reducerea activării macrofagelor, a nivelului citokinelor inflamatorii și a moleculelor de adeziune celulară, limitând astfel autoagresiunea și pasajul celulelor implicate în imunitate prin bariera sânge-nerv.

Guillain‑Barré syndrome associated with Covid‑19: A close relationship or just a coincidence? (Review)

“…Approximately one-third of the patients with GBS associated with COVID-19 required mechanical ventilation, a higher number than data from other studies ( 6 ) with GBS cases, suggesting an interaction between pneumonitis with hypoxia and weakness of respiratory muscles, which aggravates the condition of these patients ( 4 , 8 ). Uncini et al reported similar data, with one-third of the patients having respiratory failure and 85.7% of them needing mechanical ventilation ( 39 ).…”

Guillain‑Barré syndrome associated with Covid‑19: A close relationship or just a coincidence? (Review)

“…Approximately one-third of the patients with GBS associated with COVID-19 required mechanical ventilation, a higher number than data from other studies ( 6 ) with GBS cases, suggesting an interaction between pneumonitis with hypoxia and weakness of respiratory muscles, which aggravates the condition of these patients ( 4 , 8 ). Uncini et al reported similar data, with one-third of the patients having respiratory failure and 85.7% of them needing mechanical ventilation ( 39 ).…”

Guillain–Barré Syndrome in Older People—A Case Report and Literature Review

“…PE machines directly remove the antibodies and other potentially injurious factors from the blood stream [ 66 ]. IVIG therapy reduces antibodies and inflammatory cytokines levels and down-regulates macrophage activity and cell adhesion molecules to limit the self-harm induced by the passage of autoimmune cells through the blood–nerve barrier [ 67 ]. In a recent systematic review and meta-analysis, there was no significant difference between IVIG or PE therapies in terms of curative effect, length of hospital stay, duration of mechanical ventilation, risk of GBS relapse or risk of complications related to the treatment regimens.…”

The Occurrence of Acute Disseminated Encephalomyelitis in SARS-CoV-2 Infection/Vaccination: Our Experience and a Systematic Review of the Literature

“…ADEM diagnosis is made based on clinical and radiological features, and the differential diagnosis should include other inflammatory demyelinating diseases of the CNS like multiple sclerosis, neuromyelitis spectrum disorder (NMOSD), autoimmune encephalitis, antiphospholipid antibody syndrome, vasculitis secondary to rheumatic autoimmune disease, tumor, neurosarcoidosis, neuro-Bechet disease, viral encephalopathies, progressive multifocal leukoencephalopathy, adult-onset leukodystrophies, eclampsia, tick-borne etiologies, abscess or viral infections [ 4 , 8 , 14 , 74 , 116 , 117 , 118 , 119 ], and MS. Around 15% of adult patients may experience recurrences, and 25% were reported to have developed multiple sclerosis within 5 years of their initial ADEM event [ 14 , 118 , 119 ].…”

“…The response to corticosteroids is favorable in two thirds of cases, and it shortens the duration of the disease and stops further progression. In case of inadequate response, and in refractory cases, therapeutic plasma exchange or IVIg (0.4/kg/body weight) can be recommended according to the protocol applied in other autoimmune neurological diseases [ 12 , 117 , 120 , 121 , 122 ].…”

Guillain‑Barré syndrome associated with Covid‑19: A close relationship or just a coincidence? (Review)

“…Approximately one-third of the patients with GBS associated with COVID-19 required mechanical ventilation, a higher number than data from other studies ( 6 ) with GBS cases, suggesting an interaction between pneumonitis with hypoxia and weakness of respiratory muscles, which aggravates the condition of these patients ( 4 , 8 ). Uncini et al reported similar data, with one-third of the patients having respiratory failure and 85.7% of them needing mechanical ventilation ( 39 ).…”

Guillain–Barré Syndrome in Older People—A Case Report and Literature Review

“…PE machines directly remove the antibodies and other potentially injurious factors from the blood stream [ 66 ]. IVIG therapy reduces antibodies and inflammatory cytokines levels and down-regulates macrophage activity and cell adhesion molecules to limit the self-harm induced by the passage of autoimmune cells through the blood–nerve barrier [ 67 ]. In a recent systematic review and meta-analysis, there was no significant difference between IVIG or PE therapies in terms of curative effect, length of hospital stay, duration of mechanical ventilation, risk of GBS relapse or risk of complications related to the treatment regimens.…”

The Occurrence of Acute Disseminated Encephalomyelitis in SARS-CoV-2 Infection/Vaccination: Our Experience and a Systematic Review of the Literature

“…ADEM diagnosis is made based on clinical and radiological features, and the differential diagnosis should include other inflammatory demyelinating diseases of the CNS like multiple sclerosis, neuromyelitis spectrum disorder (NMOSD), autoimmune encephalitis, antiphospholipid antibody syndrome, vasculitis secondary to rheumatic autoimmune disease, tumor, neurosarcoidosis, neuro-Bechet disease, viral encephalopathies, progressive multifocal leukoencephalopathy, adult-onset leukodystrophies, eclampsia, tick-borne etiologies, abscess or viral infections [ 4 , 8 , 14 , 74 , 116 , 117 , 118 , 119 ], and MS. Around 15% of adult patients may experience recurrences, and 25% were reported to have developed multiple sclerosis within 5 years of their initial ADEM event [ 14 , 118 , 119 ].…”

“…The response to corticosteroids is favorable in two thirds of cases, and it shortens the duration of the disease and stops further progression. In case of inadequate response, and in refractory cases, therapeutic plasma exchange or IVIg (0.4/kg/body weight) can be recommended according to the protocol applied in other autoimmune neurological diseases [ 12 , 117 , 120 , 121 , 122 ].…”

Guillain‑Barré syndrome associated with Covid‑19: A close relationship or just a coincidence? (Review)

“…Approximately one-third of the patients with GBS associated with COVID-19 required mechanical ventilation, a higher number than data from other studies ( 6 ) with GBS cases, suggesting an interaction between pneumonitis with hypoxia and weakness of respiratory muscles, which aggravates the condition of these patients ( 4 , 8 ). Uncini et al reported similar data, with one-third of the patients having respiratory failure and 85.7% of them needing mechanical ventilation ( 39 ).…”

Guillain–Barré Syndrome in Older People—A Case Report and Literature Review

“…PE machines directly remove the antibodies and other potentially injurious factors from the blood stream [ 66 ]. IVIG therapy reduces antibodies and inflammatory cytokines levels and down-regulates macrophage activity and cell adhesion molecules to limit the self-harm induced by the passage of autoimmune cells through the blood–nerve barrier [ 67 ]. In a recent systematic review and meta-analysis, there was no significant difference between IVIG or PE therapies in terms of curative effect, length of hospital stay, duration of mechanical ventilation, risk of GBS relapse or risk of complications related to the treatment regimens.…”

The Occurrence of Acute Disseminated Encephalomyelitis in SARS-CoV-2 Infection/Vaccination: Our Experience and a Systematic Review of the Literature

“…ADEM diagnosis is made based on clinical and radiological features, and the differential diagnosis should include other inflammatory demyelinating diseases of the CNS like multiple sclerosis, neuromyelitis spectrum disorder (NMOSD), autoimmune encephalitis, antiphospholipid antibody syndrome, vasculitis secondary to rheumatic autoimmune disease, tumor, neurosarcoidosis, neuro-Bechet disease, viral encephalopathies, progressive multifocal leukoencephalopathy, adult-onset leukodystrophies, eclampsia, tick-borne etiologies, abscess or viral infections [ 4 , 8 , 14 , 74 , 116 , 117 , 118 , 119 ], and MS. Around 15% of adult patients may experience recurrences, and 25% were reported to have developed multiple sclerosis within 5 years of their initial ADEM event [ 14 , 118 , 119 ].…”

“…The response to corticosteroids is favorable in two thirds of cases, and it shortens the duration of the disease and stops further progression. In case of inadequate response, and in refractory cases, therapeutic plasma exchange or IVIg (0.4/kg/body weight) can be recommended according to the protocol applied in other autoimmune neurological diseases [ 12 , 117 , 120 , 121 , 122 ].…”