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Antibodies against peripheral nerve antigens in chronic inflammatory demyelinating polyradiculoneuropathy.

ABSTRACT: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous disease in which diverse autoantibodies have been described but systematic screening has never been performed. Detection of CIDP-specific antibodies may be clinically useful. We developed a screening protocol to uncover novel reactivities in CIDP. Sixty-five CIDP patients and 28 controls were included in our study. Three patients (4.6%) had antibodies against neurofascin 155, four (6.2%) against contactin-1 and one (1.5%) against the contactin-1/contactin-associated protein-1 complex. Eleven (18.6%) patients showed anti-ganglioside antibodies, and one (1.6%) antibodies against peripheral myelin protein 2. No antibodies against myelin protein zero, contactin-2/contactin-associated protein-2 complex, neuronal cell adhesion molecule, gliomedin or the voltage-gated sodium channel were detected. In IgG experiments, three patients (5.3%) showed a weak reactivity against motor neurons; 14 (24.6%) reacted against DRG neurons, four of them strongly (7.0%), and seven (12.3%) reacted against Schwann cells, three of them strongly (5.3%). In IgM experiments, six patients (10.7%) reacted against DRG neurons, while three (5.4%) reacted against Schwann cells. However, results were not statistically significant when compared to controls. Immunoprecipitation experiments identified CD9 and L1CAM as potential antigens, but reactivity could not be confirmed with cell-based assays. In summary, we describe a diverse autoantibody repertoire in CIDP patients, reinforcing the hypothesis of CIDP's pathophysiological heterogeneity.

SUBMITTER: Querol L

PROVIDER: S-EPMC5663697 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Antibodies against peripheral nerve antigens in chronic inflammatory demyelinating polyradiculoneuropathy.

Querol Luis L Siles Ana M AM Alba-Rovira Roser R Jáuregui Agustín A Devaux Jérôme J Faivre-Sarrailh Catherine C Araque Josefa J Rojas-Garcia Ricard R Diaz-Manera Jordi J Cortés-Vicente Elena E Nogales-Gadea Gisela G Navas-Madroñal Miquel M Gallardo Eduard E Illa Isabel I

Scientific reports 20171031 1

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a heterogeneous disease in which diverse autoantibodies have been described but systematic screening has never been performed. Detection of CIDP-specific antibodies may be clinically useful. We developed a screening protocol to uncover novel reactivities in CIDP. Sixty-five CIDP patients and 28 controls were included in our study. Three patients (4.6%) had antibodies against neurofascin 155, four (6.2%) against contactin-1 and o ...[more]

PMID: 29089585

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Project description:As reliable biomarkers of disease activity are lacking, monitoring of therapeutic response in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) remains a challenge. We sought to determine whether nerve ultrasound and electrophysiology scoring could close this gap. In CIDP patients (fulfilling EFNS/PNS criteria), we performed high-resolution nerve ultrasound to determine ultrasound pattern sum scores (UPSS) and predominant echotexture nerve conduction study scores (NCSS) as well as Medical Research Council sum scores (MRCSS) and inflammatory neuropathy cause and treatment disability scores (INCAT) at baseline and after 12 months of standard treatment. We retrospectively correlated ultrasound morphology with nerve histology when available. 72/80 CIDP patients featured multifocal nerve enlargement, and 35/80 were therapy-naïve. At baseline, clinical scores correlated with NCSS (r2?=?0.397 and r2?=?0.443, p?<?0.01), but not or hardly with UPSS (Medical Research Council sum scores MRCSS r2?=?0.013, p?=?0.332; inflammatory neuropathy cause and treatment disability scores INCAT r2?=?0.053, p?=?0.048). Longitudinal changes in clinical scores, however, correlated significantly with changes in both UPSS and NCSS (r2?=?0.272-0.414, p?<?0.0001). Combining nerve/fascicle size with echointensity and histology at baseline, we noted 3 distinct classes: 1) hypoechoic enlargement, reflecting active inflammation and onion bulbs; 2) nerve enlargement with additional hyperechogenic fascicles/perifascicular tissue in >?50% of measured segments, possibly reflecting axonal degeneration; and 3) almost no enlargement, reflecting "burned-out" or "cured" disease without active inflammation. Clinical improvement after 12 months was best in patients with pattern 1 (up to 75% vs up to 43% in pattern 2/3, Fisher's exact test p?<?0.05). Nerve ultrasound has additional value not only for diagnosis, but also for classification of disease state and may predict treatment response.

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.

Dataset Information

Antibodies against peripheral nerve antigens in chronic inflammatory demyelinating polyradiculoneuropathy.

Publications

Antibodies against peripheral nerve antigens in chronic inflammatory demyelinating polyradiculoneuropathy.

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