Immunotherapy of Guillain-Barré syndrome

Abstract

Guillain-Barré syndrome (GBS), the most common cause of acute neuromuscular weakness and paralysis worldwide, encompasses a group of acute immune-mediated disorders restricted to peripheral nerves and roots. Immune-mediated attack of peripheral nervous system myelin, axons or both is presumed to be triggered by molecular mimicry, with both cell- and humoral-dependent mechanisms implicated in disease pathogenesis. Good circumstantial evidence exists for a pathogenic role for molecular mimicry in GBS pathogenesis, especially with its axonal forms, providing insights that could guide future immunotherapy. Intravenous immunoglobulin (IVIg) and plasma exchange (PE) are the most commonly prescribed immunotherapies for GBS with variable efficacy dependent on GBS subtype, severity at initial presentation and other clinical and electrophysiologic prognostic factors. The mechanisms of action of IVIg and PE are not known definitely. Despite recent significant advances in molecular biology that provide insights into GBS pathogenesis, no advances in therapeutics or significant improvements in patient outcomes have occurred over the past three decades. We summarize the clinical aspects of GBS, its current pathogenesis and immunotherapy, and highlight the potential of leukocyte trafficking inhibitors as novel disease-specific immunotherapeutic drugs.

Therapeutic Plasma Exchange as a Treatment for Autoimmune Neurological Disease

“…In NMOSD, these factors include anti-AQP4 seronegativity (patients who are seronegative for anti-AQP4 but seropositive for anti-myelin oligodendrocyte glycoprotein generally present better outcomes) [12] and combination treatments with immunosuppressants [34]. In GBS, additional factors include the number of exchanges on the basis of the severity of disease [35] and the patient's age [17]. An efficient diagnosis approach [14] and early therapy initiation are common characteristics in various studies [12,14,33,35,36].…”

“…In GBS, additional factors include the number of exchanges on the basis of the severity of disease [35] and the patient's age [17]. An efficient diagnosis approach [14] and early therapy initiation are common characteristics in various studies [12,14,33,35,36].…”

Guillain-Barre Syndrome and Miller Fisher Variant in Zika Virus Disease

“…The immune system will be stimulated secondary to infectious antigen with Campylobacter jejuni (C. jejuni) being the most common infectious pathogenic agent which account for 25-50% of adult GBS cases [9]. These infectious antigens cause stimulation of both cellular and hormonal systems leading to axonal damage and demyelination of the peripheral nerve and nerve roots ( Figure 1) [11].…”

“…Monocytes, T-cells, especially CD4+ T-helper cells and B-cells in order of frequency, have been commonly implicated in the immunopathology of GBS cases especially in the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) [11].…”

“…More than 80% of the patients with Miller Fisher syndrome have anti-GQ1b IgG antibodies which mainly activate the compliment system especially at the presynaptic nerve ending and perisynaptic Schwann cells which has been implicated in the pathogenesis of MFS [11,12].…”