Increased circulating T cell reactivity to GM1 ganglioside in patients with Guillain–Barré syndrome

Abstract

This study was performed to determine whether increased ganglioside-specific T cell reactivity can be detected in the peripheral blood of patients with Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). T cell responsiveness to the gangliosides GM1, GM3, GD1a, GD1b, GD3, GT1b, GQ1b and sulphatide was assessed in peripheral blood mononuclear cells from untreated GBS patients (57), CIDP patients (43), patients with other peripheral neuropathies (55) and healthy control subjects (74) in a standard 6-day proliferation assay. Increased T cell reactivity to GM1 occurred in GBS patients compared to healthy controls and patients with other neuropathies. There was increased reactivity to GM3 in GBS patients compared to patients with other neuropathies but not compared to healthy controls. The frequencies of increased T cell reactivity to GM1 and GM3 in CIDP patients were intermediate between those of GBS patients and controls. We suggest that T cell reactivity to gangliosides might play a contributory role in the pathogenesis of GBS and perhaps CIDP.

A case of fatal Guillain–Barre syndrome from anti-PD1 monoclonal antibody use

“…Immune response directed against the myelin or axon of the peripheral nerve is implicated in the pathogenesis of GBS (Yuki and Hartung 2012). Nivolumab can cause disruption in normal immune checkpoint molecule function resulting in decreased peripheral tolerance to ganglioside-related epitopes and unchecked immune responses (Csurhes et al 2005). With increasing use of nivolumab in advanced malignancies, physicians should be aware of rare adverse events like GBS, which can be effectively treated with rapid initiation of corticosteroids, IVIG or plasma exchange along with discontinuation of anti-PD1 antibody therapy.…”

Guillain-Barre syndrome after generalized tetanus infection

“…10 Therefore, the suspected mechanism of GBS after tetanus infection in our cases is that the tetanus toxin induced T cell attacks on ganglioside. 9 However, in our patients, the tetanus was treated with TIG, which precluded our ability to determine whether GBS development was due to the tetanus infection itself or the TIG. This limitation of our study requires further research on the pathophysiology of GBS that occurs after tetanus infection.…”

“…8 Ganglioside-specific T cell reactivity is an important cause of damage to nerves through several mechanisms, including direct axonal or schwann cell cytotoxicity and secretion of proinflammatory cytokines, which induce damage directly and indirectly by recruitment and activation of macrophages. 9 The terminal part of the carboxyl group in the heavy chain of the tetanus toxin (tetanospasmin) is a strong inducer of T cell activity and has an affinity for ganglioside in peripheral nerves. 10 Therefore, the suspected mechanism of GBS after tetanus infection in our cases is that the tetanus toxin induced T cell attacks on ganglioside.…”

The role of cytokines in Guillain–Barré syndrome

“…In GBS patients, serum IFN-c was found elevated [29]. Although a significantly increased antigen specific peripheral blood mononuclear cells (PBMC) proliferation was not shown, PBMC secreting IFN-c spontaneously elevated in 25% of patients of GBS, which indicated a role of T cells in the immunopathology of GBS [30]. Moreover, neutralizing auto-antibodies to IFN-c are significantly correlated with down-regulation of IFN-c producing cells and with improved clinical disability in GBS patients [31].…”