Antiganglioside antibodies and their pathophysiological effects on Guillain-Barre syndrome and related disorders--A review

Abstract

Guillain-Barré syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy which can cause acute quadriplegia. Infection with micro-organisms, including Campylobacter jejuni (C. jejuni), Haemophilus influenzae, and Cytomegalovirus (CMV), is recognized as a main triggering event for the disease. Lipooligosaccharide (LOS) genes are responsible for the formation of human ganglioside-like LOS structures in infectious micro-organisms that can induce GBS. Molecular mimicry of LOSs on the surface of infectious agents and of ganglioside antigens on neural cells is thought to induce cross-reactive humoral and cellular immune responses. Patients with GBS develop antibodies against those gangliosides, resulting in autoimmune targeting of peripheral nerve sites, leading to neural damage. Heterogeneity of ganglioside expression in the peripheral nervous system (PNS) may underlie the differential clinical manifestation of the GBS variants. Recent studies demonstrate that some GBS sera react with ganglioside complexes consisting of two different gangliosides, such as GD1a and GD1b, or GM1 and GD1a, but not with each constituent ganglioside alone. The discovery of antiganglioside complex antibodies not only improves the detection rate of autoantibodies in GBS, but also provides a new concept in the antibody-antigen interaction through clustered carbohydrate epitopes. Although ganglioside mimicry is one of the possible etiological causes of GBS, unidentified factors may also contribute to the pathogenesis of GBS. While GBS is not considered a genetic disease, host factors, particularly human lymphocyte antigen type, appear to have a role in the pathogenesis of GBS following C. jejuni infection.

Toll-like receptor 2 and -4 are involved in the pathogenesis of the Guillain-Barré syndrome

“…LPS is recognized by TLRs (13) and therefore, TLRs may be involved in the pathogenesis of GBS. Recent evidence has suggested that anti-ganglioside antibodies are associated with the pathogenesis of GBS (14).…”

Expression of Early Growth Response Gene-2 and Regulated Cytokines Correlates with Recovery from Guillain–Barré Syndrome

“…The bacteria Campylobacter jejuni has been shown to have ganglioside-like structures in its LPS coat (10). Similar examples of molecular mimicry are seen with other organisms that trigger GBS such as Haemophilus bacteria and CMV (11). In addition, different types of viral hepatitis have been related to GBS (12).…”

“…Strong evidence support a role for Th17 and IL-17 response in GBS (5)(6)(7)(8)(9), and that axonal subtypes of GBS, AMAN, and AMSAN are caused by Abs to gangliosides on the axolemma that target macrophages to invade the axon at the node of Ranvier (2). About one-quarter of patients with GBS have suffered a recent bacterial or viral infection, and axonal forms of the disease are especially common in these patients (2,(10)(11)(12)(13)(14). The bacteria Campylobacter jejuni has been shown to have ganglioside-like structures in its LPS coat (10).…”

No evidence of a link between influenza vaccines and Guillain–Barre syndrome–associated antiganglioside antibodies

“…The clinical features of certain subtypes of GBS are composed of a myriad of pathologic subtypes, each of which is associated with specific antiganglioside antibodies; 20 thus, the inclusion of three single gangliosides – GM‐1, GM‐2, and GD1a – and the omission of others reduced the range of detection of antiganglioside antibodies associated with GBS. Furthermore, sera from GBS‐afflicted individuals react more readily to mixtures of gangliosides, known as ganglioside complexes, and not to their individual constituents 20 , 31 , 32 . In addition, this study and others 23 , 25 , 32 , 33 have utilized gangliosides of bovine brain origin for antibody detection in mouse and human sera with success.…”

“…To our knowledge, screening of antiganglioside antibodies has been performed only in persons presenting with clinical signs of GBS; therefore, the baseline levels of antiganglioside antibodies in the population remain unknown. Although antiganglioside antibodies involved with GBS cannot be treated as a definitive marker for the syndrome, they potentially play a key role in its pathophysiology, and their importance must not be underestimated 3 , 4 , 20 , 22 , 31 , 32 , 33 , 36 …”