Role Of Antiganglioside Antibodies Research Articles

Induction of broadly reactive influenza antibodies increases susceptibility to autoimmunity.

Infection and vaccination repeatedly expose individuals to antigens that are conserved between influenza virus subtypes. Nevertheless, antibodies recognizing variable influenza epitopes greatly outnumber antibodies reactive against conserved epitopes. Elucidating factors contributing to the paucity of broadly reactive influenza antibodies remains a major obstacle for developing a universal influenza vaccine. Here, we report that inducing broadly reactive influenza antibodies increases autoreactive antibodies in humans and mice and exacerbates disease in four distinct models of autoimmune disease. Importantly, transferring broadly reactive influenza antibodies augments disease in the presence of inflammation or autoimmune susceptibility. Further, broadly reactive influenza antibodies spontaneously arise in mice with defects in B cell tolerance. Together, these data suggest that self-tolerance mechanisms limit the prevalence of broadly reactive influenza antibodies, which can exacerbate disease in the context of additional risk factors.

Physiology of gangliosides and the role of antiganglioside antibodies in human diseases.

Gangliosides are structurally and functionally polymorphic sialic acid containing glycosphingolipids that are widely distributed in the human body. They play important roles in protecting us against immune attacks, yet they can become targets for autoimmunity and act as receptors for microbes, like the influenza viruses, and toxins, such as the cholera toxin. The expression patterns of gangliosides vary in different tissues, during different life periods, as well as in different animals. Antibodies against gangliosides (AGA) can target immune attack e.g., against neuronal cells and neutralize their complement inhibitory activity. AGAs are important especially in acquired demyelinating immune-mediated neuropathies, like Guillain–Barré syndrome (GBS) and its variant, the Miller–Fisher syndrome (MFS). They can emerge in response to different microbial agents and immunological insults. Thereby, they can be involved in a variety of diseases. In addition, antibodies against GM3 were found in the sera of patients vaccinated with Pandemrix®, who developed secondary narcolepsy, strongly supporting the autoimmune etiology of the disease.

Role of Anti-ganglioside Antibodies in the Diagnosis of Guillain-Barré Syndrome as an Alternate Investigation.

ObjectiveThe goal of the study was to see if anti-ganglioside antibodies have a role in the diagnosis of Guillain-Barré syndrome (GBS).Study designBetween May 2016 to October 2017, we conducted a prospective pilot study of 15 patients with a clinical diagnosis of GBS with equivocal cerebrospinal fluid (CSF) analysis and/or nerve conduction studies (NCS) .Materials and methodsAll adult patients (age >18 years) whose clinical diagnosis was GBS but diagnostic tests (either NCS or CSF analysis or both) were not suggestive of GBS were included in the study and were tested for anti-gangliosides antibodies. Data was entered in SPSS, version 21.0 (IBM, Armonk, New York) and analyzed.ResultsOf the 15 patients fulfilling the inclusion criteria, 60% had a normal CSF analysis while 40% had normal NCS. The percentages of different GBS variants observed in sampled patients were acute inflammatory demyelinating polyradiculopathy (AIDP) 40%, acute motor axonal neuropathy (AMAN) 40%, acute motor and sensory axonal neuropathy (AMSAN) 13.3%, and Miller Fisher syndrome 6.7%. However, the anti-ganglioside antibodies were negative in all patients.ConclusionAnti-gangliosides antibodies cannot be used as an alternative diagnostic investigation in GBS patients as our study failed to show positive results in different GBS variants.

The translation of the pathological findings described in humans to experimental models of acute motor axonal neuropathy

Our mechanistic understanding of the Guillain-Barre' syndromes (GBS) was greatly enhanced by the human pathological studies of Jack Griffin and colleagues conducted in the mid-1990s. Subsequently, many of the pathological findings in human GBS were confirmed and extended in animal models. This brief account of GBS pathogenesis focuses on the studies that provided the mechanistic evidence for the role of anti-ganglioside antibodies and complement in injuring the motor axon in Campylobacter-associated GBS, thereby supporting the earlier seminal pathological observations.

Antiganglioside antibodies in Guillain–Barré syndrome and its related conditions

Guillain–Barré syndrome (GBS) is typically classified into two major subtypes: acute inflammatory demyelinating neuropathy and acute motor axonal neuropathy. Its most recognizable variant is Fisher syndrome. The last two decades have seen considerable advances in our understanding of GBS. Of note, various autoantibodies against ganglioside antigens have been identified and found to have significant associations with the axonal forms of GBS and Fisher syndrome. In this article, we discuss the different clinical presentations in GBS and the role of antiganglioside antibodies in their underlying pathogenesis. We also discuss the impact that antiganglioside antibodies have had in the development of experimental models and treatment modalities in GBS.

Anti-GT1b and anti-GM1 antibodies can increase after stroke but neither is associated with late post-apoplectic epilepsy.

The role of antiganglioside antibodies (AGAs) in late post-apoplectic epilepsy (LPAE) was studied. Serum AGAs from 8 patients with large lobar infarctions were serially checked for 2.5 months. Sera from another 30 patients with fronto-temporoparietal (FTP) or frontal (F) infarction were obtained 3 months to 3 years after a stroke for AGA analysis. These 30 patients were followed up for 3 years following their strokes to determine if LPAE developed. Results showed that 7/8 patients with large lobar infarction showed increase in either anti-GT1b or anti-GM1 (IgM or IgG) within a few weeks, but levels returned to the baseline 2-3 months after stroke. LPAE occurred in 9/21 patients with FTP infarction and 5/9 with F infarction. There was no difference in AGAs among patients with FTP and F infarctions. Pooled data from these 2 groups showed no correlation between AGAs and LPAE. These data document for the first time that anti-GT1b and anti-GM1 antibodies can transiently increase after stroke, but their late titers are not associated with LPAE.