Humoral and cellular immune responses to myelin protein peptides in chronic inflammatory demyelinating polyradiculoneuropathy

Sanvito, Lara; Makowska, Anna; Mahdi-Rogers, Mohamed; Hadden, Robert D.M.; Peakman, Mark; Gregson, N. A.; Nemni, Raffaello; Hughes, Richard

doi:10.1136/jnnp.2008.159798

Cited by 62 publications

(50 citation statements)

References 29 publications

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“…Based on previous results of reduced CD4+ memory subsets in GS-treated patients [17], it might be further argued that GS treatment may be efficient for this patient group. In contrast to Sanvito et al [26], we identified higher IFN-γ responses to P2 and PMP22 peptides which have been more pronounced in the atypical compared to the typical CIDP subgroup. A higher number and proportion of atypical patients might explain this discrepancy as well as the fact that we included mainly clinically unstable and newly diagnosed patients.…”

Section: Discussioncontrasting

confidence: 99%

Differences in peripheral myelin antigen-specific T cell responses and T memory subsets in atypical versus typical CIDP

Staudt

Meisel

et al. 2017

BMC Neurol

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BackgroundChronic inflammatory demyelinating polyneuropathy (CIDP) is presented by a large heterogeneity of clinical phenotypes. Around 50% of patients suffer from typical CIDP and show better therapy response than atypical variants. The goal of our study was to search for cellular immunological differences in typical versus atypical CIDP in comparison to controls.MethodsWe evaluated 26 (9 typical, 17 atypical) patients with mainly active-unstable CIDP using clinical and immunological examinations (enzyme-linked immunospot assay ELISPOT, fluorescence-activated cell sorting FACS) in comparison to 28 healthy, age-matched controls (HC). Typical or atypical CIDP measurements were compared with HC using Kruskal-Wallis test.ResultsAtypical CIDP patients showed increased frequencies of T cell subsets, especially CD4+ effector memory T cells (TEM) and CD4+ central memory T cells (TCM) as well as a tendency of higher T cell responses against the peripheral myelin antigens of PMP-22, P2, P0 and MBP peptides compared to typical CIDP. Searching for novel auto-antigens, we found that T cell responses against P0 180-199 as well as MBP 82-100 were significantly elevated in atypical CIDP patients vs. HC.ConclusionsOur results indicate differences in underlying T cell responses between atypical and typical CIDP characterized by a higher peripheral myelin antigen-specific T cell responses as well as a specific altered CD4+ memory compartment in atypical CIDP. Larger multi-center studies study are warranted in order to characterize T cell auto-reactivity in atypical CIDP subgroups in order to establish immunological markers as a diagnostic tool.

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Section: Discussioncontrasting

confidence: 99%

Differences in peripheral myelin antigen-specific T cell responses and T memory subsets in atypical versus typical CIDP

Staudt

Meisel

et al. 2017

BMC Neurol

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“…Chronic infammatory demyelinating polyradiculoneuropathy CIDP, assumed to be the chronic counterpart of acute GBS [18], is an acquired immune-mediated infammatory disorder of the PNS, with a probable autoimmune pathogenesis. In CIDP, P2 was found to be the antigen most likely involved in the immune responses due to nerve damage [23].…”

Section: Introductionmentioning

confidence: 99%

Structural and Functional Characterization of Human Peripheral Nervous System Myelin Protein P2

et al. 2010

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The myelin sheath is a tightly packed multilayered membrane structure insulating selected axons in the central and the peripheral nervous systems. Myelin is a biochemically unique membrane, containing a specific set of proteins. In this study, we expressed and purified recombinant human myelin P2 protein and determined its crystal structure to a resolution of 1.85 Å. A fatty acid molecule, modeled as palmitate based on the electron density, was bound inside the barrel-shaped protein. Solution studies using synchrotron radiation indicate that the crystal structure is similar to the structure of the protein in solution. Docking experiments using the high-resolution crystal structure identified cholesterol, one of the most abundant lipids in myelin, as a possible ligand for P2, a hypothesis that was proven by fluorescence spectroscopy. In addition, electrostatic potential surface calculations supported a structural role for P2 inside the myelin membrane. The potential membrane-binding properties of P2 and a peptide derived from its N terminus were studied. Our results provide an enhanced view into the structure and function of the P2 protein from human myelin, which is able to bind both monomeric lipids inside its cavity and membrane surfaces.

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“…No single autoantigen has been discovered, but in 20% of patients there is evidence of antibodies to P0, the major peripheral nerve myelin glycoprotein. This protein is one of the antigens capable of inducing experimental autoimmune neuritis and is the target of the immune response in immunodeficient, nonobese diabetic mice with spontaneous inflammatory neuropathy [5][6][7][8].…”

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confidence: 99%

Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy: the ICE trial

Hughes¹

2009

Expert Review of Neurotherapeutics

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Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a potentially disabling autoimmune disease causing progressive or relapsing-remitting weakness with or without sensory loss. Previous small trials demonstrated short-term benefit from intravenous immunoglobulin (IVIg), and international guidelines recommend IVIg as an option. However, evidence had been insufficient to persuade authorities to approve IVIg for use in CIDP. This article aims to review the Immune Globulin Intravenous CIDP Efficacy (ICE) trial, which was a randomized, double-blind, placebo-controlled, response-conditional crossover trial of Gamunex (intravenous immunoglobulin, 10% caprylate/chromatography purified). With 117 participants, it is the largest treatment trial ever conducted in CIDP. The results showed unequivocal short- and long-term benefit from IVIg in confirmation of previous reports. The trial also showed for the first time that continued IVIg infusion 1 g/kg every 3 weeks protected participants from relapse. Adverse events were mostly mild and serious adverse events were not more common with IVIg than with placebo. The results persuaded the US FDA and Health Canada to approve Gamunex for use in CIDP.

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Humoral and cellular immune responses to myelin protein peptides in chronic inflammatory demyelinating polyradiculoneuropathy

Cited by 62 publications

References 29 publications

Differences in peripheral myelin antigen-specific T cell responses and T memory subsets in atypical versus typical CIDP

Differences in peripheral myelin antigen-specific T cell responses and T memory subsets in atypical versus typical CIDP

Structural and Functional Characterization of Human Peripheral Nervous System Myelin Protein P2

Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy: the ICE trial

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