Association of Tumor Necrosis Factor Polymorphisms with Guillain-Barré Syndrome

Zhang, Jing; Dong, Hui; Li, Bin; Li, Chunyan; Guo, Li

doi:10.1159/000102162

Cited by 31 publications

(24 citation statements)

References 30 publications

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“…TNF-α is able to inhibit Schwann cell proliferation and mediate Schwann cell death (27). TNF-α was elevated and associated with disease severity in EAN (28) and GBS (29). In a further study, Zhang et al (30) observed that the onset of EAN in TNF-α gene-deficient mice was markedly later than that in wild type mice.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

et al. 2015

Molecular Medicine Reports

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Abstract. Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system characterized by weakness in the limbs. To date, numerous hypotheses have been suggested to explain the pathogenesis of GBS; however, the pathogenesis of GBS remains to be elucidated. The aim of the present study was to investigate the association between Toll-like receptor (TLR) 2, TLR4 and GBS. Therefore, the mRNA of TLR2, TLR4, myeloid differentiation factor (MyD)88 and nuclear factor (NF)-κB of peripheral blood mononuclear cells (PBMCs) in patients with GBS and healthy controls was assessed. To confirm the function of TLR2 and TLR4 in the pathogenesis of GBS, PBMCs derived from patients with GBS and healthy controls were cultured with various TLR agonists. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were measured in the culture supernatant and fasting serum was obtained for the detection of anti-ganglioside antibodies. The results revealed that the mRNA levels of TLR2, TLR4, MyD88 and NF-κB were significantly increased in patients with GBS compared with those in healthy controls (P=0.003, 0.017, 0.032 and 0.015, respectively). PBMCs from patients with GBS secreted higher levels of TNF-α and IL-1β than those from control subjects. The positive rate of immunoglobulin (Ig)G and IgM anti-ganglioside antibodies in patients with severe GBS was 42.86%, which was markedly higher than rates found in patients with mild GBS (9.09 and 18.18%, respectively). The results of the present study demonstrated that TLR2 and TLR4 are involved in the pathogenesis of GBS and that they and their associated signaling pathways may be targets for the treatment of GBS.

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Section: Discussionmentioning

confidence: 99%

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

Zhang

et al. 2015

Molecular Medicine Reports

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“…Association between different HLA types and GBS has been reported with preceding C. jejuni infection but has only been observed in some populations (9 -12). Polymorphisms in the TNF gene have been associated with a rare GBS subtype in a Chinese population (13), but association studies have so far failed in identifying single genes regulating the more prevalent AIDP subtype. This indicates a genetically complex regulation of GBS, and large homogeneous patient cohorts are required for accurate genetic analysis.…”

Section: G Uillain-barré Syndrome (Gbs)mentioning

confidence: 99%

Advanced Intercross Line Mapping Suggests That Ncf1 (Ean6) Regulates Severity in an Animal Model of Guillain-Barré Syndrome

Huberle

Beyeen

Öckinger

et al. 2009

The Journal of Immunology

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We here present the first genetic fine mapping of experimental autoimmune neuritis (EAN), the animal model of Guillain-Barré syndrome, in a rat advanced intercross line. We identified and refined a total of five quantitative trait loci on rat chromosomes 4, 10, and 12 (RNO4, RNO10, RNO12), showing linkage to splenic IFN-␥ secretion and disease severity. All quantitative trait loci were shared with other models of complex inflammatory diseases. The quantitative trait locus showing strongest linkage to clinical disease was Ean6 and spans 4.3 Mb on RNO12, harboring the neutrophil cytosolic factor 1 (Ncf1) among other genes. Polymorphisms in Ncf1, a member of the NADPH oxidase complex, have been associated with disease regulation in experimental arthritis and encephalomyelitis. We therefore tested the Ncf1 pathway by treating rats with a NADPH oxidase complex activator and ameliorated EAN compared the oil-treated control group. By proving the therapeutic effect of stimulating the NADPH oxidase complex, our data strongly suggest the first identification of a gene regulating peripheral nervous system inflammation. Taken together with previous reports, our findings suggest a general role of Ncf1 and oxidative burst in pathogenesis of experimental autoimmune animal models.

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“…In addition, increased proinfl ammatory cytokine levels were also found in noninfl ammatory neuropathies [ 18 , 19 ]. A link was suggested between polymorphisms in the gene of the proinfl ammatory cytokine tumor necrosis factor (TNF)-α and the occurrence of GBS [ 20 ]. There are further reports that modulation of the innate cytokine system by application of cytokines or cytokine inhibitors may cause neuropathies [ 21 , 22 ].…”

Section: Cytokines In Peripheral Neuropathiesmentioning

confidence: 99%

Status of immune mediators in painful neuropathies

Üçeyler¹,

Sommer

2008

Current Science Inc

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Peripheral neuropathies of identical etiology can be painful or painless. The reason for this difference in clinical presentation is as yet unknown; however, immune mediators, particularly cytokines, may play a role. Cytokines are proteins that are produced by immune and nonimmune cells and are categorized as pro- and anti-inflammatory. The role of cytokines in the induction and maintenance of pain has been well established in animal models. Proinflammatory cytokines are mostly algesic, whereas anti-inflammatory cytokines have analgesic properties. Clinical research also gives evidence for the involvement of cytokines in painful and painless neuropathies. A proinflammatory cytokine profile seems to be associated with pain in peripheral neuropathies of different etiologies and in other painful disorders such as the complex regional pain syndrome. Specifically, an imbalance between pro- and anti-inflammatory cytokines may contribute to pain generation. A better understanding of the underlying pathophysiology may open new opportunities for the treatment of pain.

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Association of Tumor Necrosis Factor Polymorphisms with Guillain-Barré Syndrome

Cited by 31 publications

References 30 publications

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

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

Advanced Intercross Line Mapping Suggests That Ncf1 (Ean6) Regulates Severity in an Animal Model of Guillain-Barré Syndrome

Status of immune mediators in painful neuropathies

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