Prevalence of IgG Autoantibodies against GD3 Ganglioside in Acute Zika Virus Infection

Abstract

Zika virus (ZIKV) disease has become a global health emergency with devastating effects on public health. Recent evidences implicate the virus as an emergent neuropathological agent promoting serious pathologies of the human nervous system, that include destructive and malformation consequences such as development of ocular and fetal brain lesions, microcephaly in neonates, and Guillain–Barré syndrome (GBS) in adults. These neurological disorders of both central and peripheral nervous systems are thought to be associated to the neurotropic properties of the virus that has ability to infect neural stem cells as well as peripheral neurons, a hallmark of its pathogenicity. The presence of autoantibodies against gangliosides plays a pivotal role in the etiogenesis of GBS and a variety of neurological disorders. Gangliosides are a class of galactose-containing cerebrosides mainly expressed in nervous system tissues playing a critical role in the physiology of neural cells and neurogenesis. Herein, our findings indicate that patients at acute phase of ZIKV infection without any neurological signs show increased levels of IgG autoantibody against GD3 gangliosides, a class of glycolipid found to be highly expressed in neural stem cell acting in the maintenance of their self-renewal cellular capacity. It is possible that a pathological threshold of these antibodies is only acquired in secondary or subsequent infections. In the light of these evidences, we propose that the target of GD3 by autoimmune responses may possibly has an effect in the neuropathy and neurogenesis disorder seen during ZIKV infection.

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

“…Nico et al reported anti-GD3 antibodies in acute ZIKV infections. 119 Baskar and colleagues showed anti-GM1 antibodies in 50% of ZIKV-positive patients. 120 However, Cao-Lormeau and his team showed that only a fraction of patients with GBS after ZIKV had AGAs, and their sera (anti-GA1 and GD1a) displayed no antibody competition between ZIKV proteins and GA1, a.k.a.…”

Divergent Roles of Antiself Antibodies during Infection

“…However, in addition to this, it has been proposed that the development of Zika-associated GBS may be caused by anti-self ganglioside antibodies generated during infection, highlighting a possible autoimmune-like component [28–30]. Indeed, high levels of anti-GD3 ganglioside antibodies are found in Zika patients [31]. Since Dengue and Chikungunya infections can also lead to auto-antibody production [17], it is possible that shared autoimmune triggers are present in these three infections.…”

The Association of Anti-Ganglioside Antibodies in the Pathogenesis and Development of Zika-Associated Guillain-Barré Syndrome

“…So, in 2018, Nico et al tested the serum of patients affected with ZIKV for IgG autoantibodies against brain gangliosides by ELISA. They found a several-fold increase in the level of IgG autoantibodies to brain gangliosides in these patients [9]. Rivera-Correa et al proved the same in 2019.…”

“…The pathogenesis of GBS is said to be molecular mimicry between the gangliosides and the molecules present on the surface of the infectious agents (e.g., lipopolysaccharide of Campylobacter jejuni). Autoimmunity between these gangliosides and ZIKV is what contributes to the neurological complications of this virus [9]. Not all patients infected with Zika develop neurological complications [10].…”

“…The presence of anti-ganglioside antibodies was found in patients infected with pathogens like C. jejuni, Epstein-Barr virus, and cytomegalovirus [ 9 ]. However, the association of anti-ganglioside antibodies in patients with Zika-associated GBS is still unclear.…”