Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barré syndrome

Sawai, Setsu; Satoh, Mamoru; Mori, Masahiro; Misawa, Sonoko; Sogawa, Kazuyuki; Kazami, Takahiro; Ishibashi, Masayoshi; Beppu, Minako; Shibuya, Kazumoto; Ishige, Takayuki; Sekiguchi, Yukari; Noda, Kenta; Sato, Kenichi; Matsushita, Hiroshi; Kodera, Yasuhiro; Nomura, Fumio; Kuwabara, Satoshi

doi:10.1212/wnl.0000000000000566

Cited by 53 publications

(40 citation statements)

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“…Anti-moesin IgG was not detected in five patients who had CMV infection but not GBS [26], which is in contrast to detecting anti-GM2 IgM antibodies in six of 10 (60 %) patients who had CMV infection but not GBS [10]. Although the findings by Sawai et al [26] should be validated by other investigators [27], it would be reasonable to consider that IgG antibodies, rather than IgM antibodies, are the effector molecules responsible for the development of CMV, as well as C. jejuni-related GBS and its variants.…”

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

“…Sawai et al [26] recently identified membraneorganizing extension spike protein (moesin), which is expressed in the Schwann cell processes at the nodes of Ranvier, and is crucial for myelination as a target protein for serum IgG in CMV-associated GBS. Anti-moesin IgG antibodies were detected in five (83 %) of six patients with demyelinating GBS after CMV infection, and the antibody titer decrease was confirmed using paired samples [26]. Anti-moesin IgG was not detected in five patients who had CMV infection but not GBS [26], which is in contrast to detecting anti-GM2 IgM antibodies in six of 10 (60 %) patients who had CMV infection but not GBS [10].…”

Section: Discussionmentioning

confidence: 99%

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Ambiguous value of anti-ganglioside IgM autoantibodies in Guillain-Barré syndrome and its variants

et al. 2015

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Anti-ganglioside autoantibodies of the IgG type are detected in a half of patients with Guillain-Barré syndrome (GBS), and their detection strongly supports the diagnosis of GBS. In contrast, anti-ganglioside IgM antibodies are also often detected in GBS patients, but it remains unclear whether IgM antibodies indicate a diagnosis of GBS. We identified four GBS patients (3.3%) who tested positive for IgM antibodies but negative for IgG antibodies among 122 patients with GBS and its variants. These four patients were all adolescents or young adults (age 13-22 years), experienced preceding gastrointestinal symptoms, and had serological and/or bacterial evidence of recent Campylobacter jejuni enteritis. Serum IgG reacted strongly with the lipo-oligosaccharide (LOS) of the C. jejuni isolates from these patients' stool specimens. Thin-layer chromatography with immunostaining showed that their serum IgG reacted with resorcinol-positive portion of LOS, suggesting that these patients had IgG autoantibodies against sialic acid-containing epitopes, probably unrecognized ganglioside-like structures on the bacterial LOS. We also examined anti-ganglioside autoantibodies in 22 patients with C. jejuni enteritis without subsequent neurological disorders and detected IgM antibodies in seven (32%) patients. Our data indicate that anti-ganglioside IgM antibodies can be detected in C. jejuni enteritis without complication of GBS, and that the detection of anti-ganglioside IgM antibodies does not always support a diagnosis of GBS. IgG autoantibodies against unrecognized gangliosides might play a role in the development of disease in patients with GBS in whom only anti-ganglioside IgM antibodies are detected by routine clinical testing.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Ambiguous value of anti-ganglioside IgM autoantibodies in Guillain-Barré syndrome and its variants

et al. 2015

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“…Highresolution immunocytochemistry of autopsy specimens in early stage AIDP showed complement activation marker C3d and terminal complement complex neoantigen C5b-9 along the outer surface of Schwann cells, associated with demyelination [13]. Recently, moesin has been implicated to be a target antigen for CMV related AIDP [14]. Given the proposed pathogenesis, the rarity of CMVassociated GBS in SOT patients might be due to their immunosuppressed state.…”

Section: Discussionmentioning

confidence: 99%

Late-onset cytomegalovirus infection complicated by Guillain–Barre syndrome in a kidney transplant recipient: case report and review of the literature

2015

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Cytomegalovirus (CMV) infection remains a common infection after solid-organ transplantation. In the general population CMV disease is associated with Guillain-Barre syndrome (GBS), an autoimmune disease leading to an acute peripheral neuropathy, in 1 of 1000 cases. Interestingly, GBS is a rarely observed complication in solid-organ transplant recipients, possibly related to maintenance immunosuppression. We describe a case of CMV infection complicated by GBS in a kidney transplant recipient and review the literature.

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“…Recent results showed that infection leads to antibody production, which cross-reacts with gangliosides and other glycolipids leading to myelin destruction by complement activation or by antibodies targeting macrophages via the Fc receptor and leading to both demyelination and nerve conduction failure [2, 14]. Furthermore, recent results point at pathogen-derived proteins as triggers of molecular mimicry involved in the GBS [15–17]. …”

Section: Introductionmentioning

confidence: 99%

Quantitative proteomics reveals Piccolo as a candidate serological correlate of recovery from Guillain-Barré syndrome

et al. 2016

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Guillain-Barré syndrome (GBS) is an autoimmune-mediated peripheral neuropathy of unknown cause. However, about a quarter of GBS patients have suffered a recent bacterial or viral infection, and axonal forms of the disease are especially common in these patients. Proteomics is a good methodological approach for the discovery of disease biomarkers. Until recently, most proteomics studies of GBS and other neurodegenerative diseases have focused on the analysis of the cerebrospinal fluid (CSF). However, serum represents an attractive alternative to CSF because it is easier to sample and has potential for biomarker discovery. The goal of this research was the identification of serum biomarkers associated with recovery from GBS. To address this objective, a quantitative proteomics approach was used to characterize differences in the serum proteome between a GBS patient and her healthy identical twin in order to lessen variations due to differences in genetic background, and with additional serum samples collected from unrelated GBS (N = 3) and Spinal Cord Injury (SCI) (N = 3) patients with similar medications. Proteomics results were then validated by ELISA using sera from additional GBS patients (N = 5) and healthy individuals (N = 3). All GBS and SCI patients were recovering from the acute phase of the disease. The results showed that Piccolo, a protein that is essential in the maintenance of active zone structure, constitutes a potential serological correlate of recovery from GBS. These results provided the first evidence for the Piccolo's putative role in GBS, suggesting a candidate target for developing a serological marker of disease recovery.

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Moesin is a possible target molecule for cytomegalovirus-related Guillain-Barré syndrome

Abstract: This study provides Class II evidence that levels of serum anti-moesin antibodies accurately distinguishes CMV-related AIDP from non-CMV-related AIDP (sensitivity 83%, specificity 93%).

Cited by 53 publications

References 10 publications

Ambiguous value of anti-ganglioside IgM autoantibodies in Guillain-Barré syndrome and its variants

Ambiguous value of anti-ganglioside IgM autoantibodies in Guillain-Barré syndrome and its variants

Late-onset cytomegalovirus infection complicated by Guillain–Barre syndrome in a kidney transplant recipient: case report and review of the literature

Quantitative proteomics reveals Piccolo as a candidate serological correlate of recovery from Guillain-Barré syndrome

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