Aquaporin 4, Helicobacter pylori and potential implications for neuromyelitis optica

Kountouras, Jannis; Deretzi, Georgia; Gavalas, Emmanuel; Zavos, Christos; Boziki, Marina; Tsiaousi, Elena; Stergiopoulos, Christos; Romiopoulos, Iordanis; Giorgakis, Nikolaos; Michael, Stavros; Tantsi, Nikoleta; Kotsani, Marina

doi:10.1016/j.jneuroim.2013.06.003

Cited by 7 publications

(7 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite identification of AQP4 as the principal target, the initial pathophysiologic events that lead to development of NMO have remained elusive. Besides genetic factors that may predispose to NMO, investigators have considered possible environmental triggers, including plants, bacteria, or viruses that could elicit AQP4-specific antibodies [ 8 – 10 ]. “Molecular mimicry”, which can occur when a foreign protein that shares structural or amino-acid sequence homology with a self-antigen elicits cross-reactive immunity [ 11 ], is implicated in the pathogenesis of several rheumatologic and CNS autoimmune disorders [ 12 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

The Gut Microbiome in Neuromyelitis Optica

et al. 2018

View full text Add to dashboard Cite

Neuromyelitis optica (NMO) is a rare, disabling, sometimes fatal central nervous system inflammatory demyelinating disease that is associated with antibodies (“NMO IgG”) that target the water channel protein aquaporin-4 (AQP4) expressed on astrocytes. There is considerable interest in identifying environmental triggers that may elicit production of NMO IgG by AQP4-reactive B cells. Although NMO is considered principally a humoral autoimmune disease, antibodies of NMO IgG are IgG1, a T-cell-dependent immunoglobulin subclass, indicating that AQP4-reactive T cells have a pivotal role in NMO pathogenesis. When AQP4-specific proliferative T cells were first identified in patients with NMO it was discovered that T cells recognizing the dominant AQP4 T-cell epitope exhibited a T helper 17 (Th17) phenotype and displayed cross-reactivity to a homologous peptide sequence within a protein of Clostridium perfringens, a commensal bacterium found in human gut flora. The initial analysis of gut microbiota in NMO demonstrated that, in comparison to healthy controls (HC) and patients with multiple sclerosis, the microbiome of NMO is distinct. Remarkably, C. perfringens was the second most significantly enriched taxon in NMO, and among bacteria identified at the species level, C. perfringens was the one most highly associated with NMO. Those discoveries, along with evidence that certain Clostridia in the gut can regulate the balance between regulatory T cells and Th17 cells, indicate that gut microbiota, and possibly C. perfringens itself, could participate in NMO pathogenesis. Collectively, the evidence linking microbiota to humoral and cellular immunity in NMO underscores the importance for further investigating this relationship.Electronic supplementary materialThe online version of this article (10.1007/s13311-017-0594-z) contains supplementary material, which is available to authorized users.

show abstract

Section: Introductionmentioning

confidence: 99%

The Gut Microbiome in Neuromyelitis Optica

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Common environmental determinants such as insufficient sunlight and vitamin D or numerous frequent infections, such as Helicobacter pylori ( H. pylori ) infection as initial trigger factors affect cell injury, causing autoantigen exposure and epitope mimicry, and activation of antigen‐presenting cells may contribute to concurrence of autoimmunity. In this regard, H. pylori infection might be a common environmental denominator that triggers MS‐related polyautoimmunity; H. pylori infection has been involved in MS pathophysiology and also contributes to the pathogenesis of other organ‐specific ADs (i.e., polyautoimmunity) such as Sjögren's syndrome, systemic sclerosis, autoimmune pancreatitis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, or hepatitis C virus‐related liver disease which trigger autoimmune sequelae . It is important to note that the aforementioned H. pylori ‐related autoimmunities are accompanied by a high prevalence of polyautoimmunity signifying the mentioned autoimmune tautology.…”

Section: Discussionmentioning

confidence: 99%

Polyautoimmunity in a Greek cohort of multiple sclerosis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…8 In addition, H. pylori-induced vacA cytotoxin promotes intracellular survival of the bacterium, modulates host immune responses and induces autophagy. 9 Subsequently, H. pylori, as an intracellular microorganism, invades and replicates in the cells. The autophagy induction by H. pylori is not only found in macrophages but also in dendritic cells (also expressed in acute and chronic cholecystitis) 10 and gastric epithelial cells.…”

mentioning

confidence: 99%

“…The autophagy induction by H. pylori is not only found in macrophages but also in dendritic cells (also expressed in acute and chronic cholecystitis) 10 and gastric epithelial cells. 9 The bacterium's residence inside the infected cells will increase its resistance to antimicrobial treatment, avoid neutralisation by anti-H. pylori antibodies, impair antigen presentation, and alter the cellular immune response. 9 In turn, the potential influx of activated monocytes infected with H. pylori in the gall bladder may lead to gall bladder-related pathologies; a comparable potential influx of activated monocytes infected with H. pylori through the disrupted blood-brain barrier, induced by several H. pylori-related mediators, in the brain ('Trojan Horse' pathway) might also lead to brain pathologies.…”

mentioning

confidence: 99%

“…9 The bacterium's residence inside the infected cells will increase its resistance to antimicrobial treatment, avoid neutralisation by anti-H. pylori antibodies, impair antigen presentation, and alter the cellular immune response. 9 In turn, the potential influx of activated monocytes infected with H. pylori in the gall bladder may lead to gall bladder-related pathologies; a comparable potential influx of activated monocytes infected with H. pylori through the disrupted blood-brain barrier, induced by several H. pylori-related mediators, in the brain ('Trojan Horse' pathway) might also lead to brain pathologies. 9 Moreover, comparable to H. pylori translocation from the duodenum via Oddi's sphincter to the biliary tract, mentioned by Helaly et al, 1 this bacterium may reach the brain through the oral cavity (which appears to act as a permanent reservoir for H. pylori)-nasal cavity-olfactory neuroepithelium pathway, causing central nervous system pathologies.…”

mentioning

confidence: 99%

See 1 more Smart Citation