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Therapeutic options for chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review.

ABSTRACT: Chronic inflammatory demyelinating polyradiculoneuropathy is a rare acquired immune-mediated progressive or relapsing disorder causing peripheral neuropathic disease of duration more than two months. Many individuals with chronic inflammatory demyelinating polyradiculoneuropathy fail to make a long-term recovery with current treatment regimes. The aim of this study was to prospectively review the literature to determine the effectiveness of therapies for chronic inflammatory demyelinating polyradiculoneuropathy.Articles published from January 1990 to December 2012 were searched for studies to treat adults with chronic inflammatory demyelinating polyradiculoneuropathy. Peer-reviewed full-text articles published in English were included.Nine placebo-controlled double-blinded randomised trials were reviewed to treat subjects with chronic inflammatory demyelinating polyradiculoneuropathy exhibiting various degrees of effectiveness. The most effect treatments were; three randomised controlled trials using intravenous immunoglobulin, a study comparing pulsed dexamethasone and short term prednisolone and rituximab all showed promising results and were well tolerated.IVIg and corticosteroids remain first line treatments for CIDP. Therapies using monoclonal antibodies, such as Rituximab and Natalizumab offer the most promise for treatment of Chronic inflammatory demyelinating polyradiculoneuropathy however they also need further research, as does the use of stem cell therapy for treating Chronic inflammatory demyelinating polyradiculoneuropathy. Large randomised controlled trials and better patient selection are required to address responsiveness of CIDP patients to conventional treatments to elucidate mechanisms of action and future directions for therapeutic improvement.

SUBMITTER: Bright RJ

PROVIDER: S-EPMC3925253 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Therapeutic options for chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review.

Bright Richard J RJ Wilkinson Jenny J Coventry Brendon J BJ

BMC neurology 20140207

<h4>Background</h4>Chronic inflammatory demyelinating polyradiculoneuropathy is a rare acquired immune-mediated progressive or relapsing disorder causing peripheral neuropathic disease of duration more than two months. Many individuals with chronic inflammatory demyelinating polyradiculoneuropathy fail to make a long-term recovery with current treatment regimes. The aim of this study was to prospectively review the literature to determine the effectiveness of therapies for chronic inflammatory d ...[more]

PMID: 24507546

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Project description:BackgroundHuman endogenous retroviruses HERV-W encode a pro-inflammatory protein, named MSRV-Env from its original identification in Multiple Sclerosis. Though not detected in various neurological controls, MSRV-Env was found in patients with chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs). This study investigated the expression of MSRV in CIDP and evaluated relevant MSRV-Env pathogenic effects.Methods50 CIDP patients, 19 other neurological controls (ONDs) and 65 healthy blood donors (HBDs) were recruited from two different countries. MSRV-env and -pol transcripts, IL6 and CXCL10 levels were quantified from blood samples. MSRV-Env immunohistology was performed in distal sensory nerves from CIDP and neurological controls biopsies. MSRV-Env pathogenic effects and mode of action were assayed in cultured primary human Schwann cells (HSCs).FindingsIn both cohorts, MSRV-env and -pol transcripts, IL6 positivity prevalence and CXCL10 levels were significantly elevated in CIDP patients when compared to HBDs and ONDs (statistically significant in all comparisons). MSRV-Env protein was detected in Schwann cells in 5/7 CIDP biopsies. HSC exposed to or transfected with MSRV-env presented a strong increase of IL6 and CXCL10 transcripts and protein secretion. These pathogenic effects on HSC were inhibited by GNbAC1, a highly specific and neutralizing humanized monoclonal antibody targeting MSRV-Env.InterpretationThe present study showed that MSRV-Env may trigger the release of critical immune mediators proposed as instrumental factors involved in the pathophysiology of CIDP. Significant MSRV-Env expression was detected in a significant proportion of patients with CIDP, in which it may play a role according to its presently observed effects on Schwann cells along with previously known effects on immune cells. Experimental results also suggest that a biomarker-driven therapeutic strategy targeting this protein with a neutralizing antibody such as GNbAC1 may offer new perspectives for treating CIDP patients with positive detection of MSRV-Env expression.FundingGeneuro-Innovation, France.

Project description:Objectives: To review the available evidence on sensitivity and specificity of anti-NF155 antibody detection in diagnosing a specific subset of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and to calculate the frequencies of different autoantibodies to paranodal proteins. Background: Diagnosis of CIDP relies on clinical and neurophysiologic criteria and lacks useful diagnostic biomarkers. A subset of CIDP patients exhibit atypical clinical phenotypes and impaired response to conventional treatments. These patients were reported as having autoantibodies targeting paranodal protein neurofascin isoform 155 (NF155), contactin-1 (CNTN1), and contactin-associated protein-1 (CASPR1). Here, we conducted a meta-analysis to summarize evidence on the diagnostic and prognostic value of these autoantibodies, especially for anti-NF155 antibody. Methods: We searched the following electronic bibliographic databases: PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science. Eligible studies provided information to calculate the frequencies of anti-NF155 antibody and anti-CNTN1 antibody, the sensitivity and specificity of anti-NF155 antibody, and the incidence of improvement and deterioration among anti-NF155 antibody seropositive CIDP patients. Heterogeneity was assessed using Q and I 2 statistics. Results: The pooled frequency of anti-NF155 autoantibody across 14 studies was 7% [95% confidence interval (CI): 0.05-0.10] with high heterogeneity; the overall pooled sensitivity and specificity of anti-NF155 antibody for the diagnosis of a specific subgroup of CIDP patients were 0.45 (95% CI: 0.29-0.63) and 0.93 (95% CI: 0.86-0.97), respectively. Conclusions: For diagnosing of a specific subset of CIDP characterized by poor response to intravenous immunoglobulin (IVIg), we found a moderate sensitivity and a high specificity. The anti-NF155 antibody test should be used as a confirmatory test rather than a screening test. Systematic Review Registration: PROSPERO, identifier: CRD42020203385 and CRD42020190789.

Dataset Information

Therapeutic options for chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review.

Publications

Therapeutic options for chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review.

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