Remarkable Rituximab Response on Tremor Related to Acute‐Onset Chronic Inflammatory Demyelinating Polyradiculoneuropathy in an Antineurofascin155 Immunoglobulin G4–Seropositive Patient

Demichelis, Chiara; Franciotta, Diego; Cortese, Andrea; Callegari, Ilaria; Serrati, Carlo; Mancardi, Gianluigi; Schenone, Angelo; Leonardi, Alessandro; Benedetti, Luana

doi:10.1002/mdc3.12662

Cited by 8 publications

(7 citation statements)

References 7 publications

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“…CIDP associated with IgG4 anti-CNTN1 antibodies have a more frequent acute or subacute onset than those associated with IgG4 anti-Nfasc155. Postural tremor was present in 4/10 of our patients and reported in 3/4 patients in a previous study [12], but this seems less disabling than that reported in CIDP associated with IgG4 anti-Nfasc155 [22,23]. Our patients with anti-CNTN1 antibodies had frequent bifacial palsy.…”

Section: Discussionsupporting

confidence: 43%

Antibodies against the node of Ranvier: a real-life evaluation of incidence, clinical features and response to treatment based on a prospective analysis of 1500 sera

et al. 2020

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Introduction IgG4 antibodies against neurofascin (Nfasc155 and Nfasc140/186), contactin (CNTN1) and contactin-associated protein (Caspr1) are described in specific subtypes of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Our objective was to assess, in a real-life practice, the incidence, the clinical features and the response to treatment of these forms of CIDP. Methods 1500 sera of patients suspected of having CIDP from France, Belgium and Switzerland were prospectively tested using a flow cytometry technique. The characteristics of patients with antibodies against the node of Ranvier were compared to 100 seronegative CIDP from our department. Results IgG4 antibodies against Nfasc155, CNTN1, and Caspr1 were, respectively, detected in 15 (prevalence 1%), 10 (0.7%) and 2 (0.2%) sera. Antibodies specific of the Nfasc140/186 were not detected. All subjects with antibodies against the node of Ranvier fulfilled diagnostic criteria for CIDP. CIDP with anti-Nfasc155 were younger, had more sensory ataxia and postural tremor than seronegative CIDP. CIDP with anti-CNTN1 had more frequent subacute onset and facial paralysis, commoner renal involvement with membranous glomerulonephritis and greater disability, than seronegative CIDP. CIDP with anti-Caspr1 had more frequent respiratory failure and cranial nerve involvement but not more neuropathic pain than seronegative CIDP. Intravenous immunoglobulins were ineffective in most seropositive patients. Rituximab produced dramatic improvement in disability and decreased antibodies titres in 13 seropositive patients (8 with anti-Nfasc155 and 5 with anti-CNTN1 antibodies). Conclusions Although rare, anti-paranodal antibodies are clinically valuable, because they are associated with specific phenotypes and therapeutic response.

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Section: Discussionsupporting

confidence: 43%

Antibodies against the node of Ranvier: a real-life evaluation of incidence, clinical features and response to treatment based on a prospective analysis of 1500 sera

et al. 2020

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“…Rituximab has previously been suggested as an effective treatment for paranodal antibody positive patients [42,43], but may take several weeks (or even months) to produce benefit. In this case, a second cycle of IA, 4 weeks after a course of rituximab, produced a more persistent suppression of antibody titres, which was associated with clinical improvement.…”

Section: Discussionmentioning

confidence: 99%

Immunoadsorption and Plasma Exchange in Seropositive and Seronegative Immune-Mediated Neuropathies

Davies

Fehmi

Şenel

et al. 2020

JCM

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The inflammatory neuropathies are disabling conditions with diverse immunological mechanisms. In some, a pathogenic role for immunoglobulin G (IgG)-class autoantibodies is increasingly appreciated, and immunoadsorption (IA) may therefore be a useful therapeutic option. We reviewed the use of and response to IA or plasma exchange (PLEx) in a cohort of 41 patients with nodal/paranodal antibodies identified from a total of 573 individuals with suspected inflammatory neuropathies during the course of routine diagnostic testing (PNAb cohort). 20 patients had been treated with PLEx and 4 with IA. Following a global but subjective evaluation by their treating clinicians, none of these patients were judged to have had a good response to either of these treatment modalities. Sequential serology of one PNAb+ case suggests prolonged suppression of antibody levels with frequent apheresis cycles or adjuvant therapies, may be required for effective treatment. We further retrospectively evaluated the serological status of 40 patients with either Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP), and a control group of 20 patients with clinically-isolated syndrome/multiple sclerosis (CIS/MS), who had all been treated with IgG-depleting IA (IA cohort). 32 of these patients (8/20 with CIDP, 13/20 with GBS, 11/20 with MS) were judged responsive to apheresis despite none of the serum samples from this cohort testing positive for IgG antibodies against glycolipids or nodal/paranodal cell-adhesion molecules. Although negative on antigen specific assays, three patients’ pre-treatment sera and eluates were reactive against different components of myelinating co-cultures. In summary, preliminary evidence suggests that GBS/CIDP patients without detectable IgG antibodies on routine diagnostic tests may nevertheless benefit from IA, and that an unbiased screening approach using myelinating co-cultures may assist in the detection of further autoantibodies which remain to be identified in such patients.

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“…The weakness was mild to moderate and predominantly localized at distal sites. Recent reports have described additional features, such as head and tongue tremors 33‐35 . Laboratory findings showed that antibody‐positive patients had remarkably high CSF protein levels, usually >200 mg/dL, whereas seronegative patients commonly had levels <100 mg/dL 22,36 .…”

Section: Clinical Features Of Patients With Antibodies Against Node Omentioning

confidence: 99%

Treatment of chronic inflammatory demyelinating polyradiculoneuropathy patients with antibodies against paranodal proteins

Iijima

2020

Clinical & Exp Neuroim

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Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune‐mediated polyneuropathy characterized by relapsing or steadily progressive clinical course. A major feature of the syndrome is that it encompasses several pathogeneses, and it is actually assumed that both cellular and humoral immunity can be involved with superiority depending on the particular subtype. Although cellular immunity typified by macrophage‐derived demyelination can play an essential role in classical CIDP, other pathogeneses that involve humoral immunity, such as autoantibodies targeting node of Ranvier proteins (neurofascin155: NF155; contactin1: CNTN1; contactin‐associated protein1: Caspr1; and neurofascin186/140: NF186/140), can bring about functional demyelination and have been discovered in approximately 5–15% of CIDP patients. Interestingly, such antibodies commonly belong to the immunoglobulin G4 (IgG4) subclass, and thus lack complement‐binding sites and compete with other IgG subclasses for the antigens. Patients with these IgG4 autoantibodies share clinical presentations to a certain extent, and anti‐NF155 and anti‐CNTN1 antibodies are representative examples. Patients with these IgG4 subclass antibodies fulfill the conservative diagnostic criteria for CIDP: distal‐dominant weakness, tremor and sensory ataxia. These patients also show poor responses to conventional first‐line therapeutics, and are non‐responders to intravenous immunoglobulins in particular. Therefore, novel treatment strategies other than first‐line therapies are awaited, and to date, small retrospective studies and several case reports have suggested the efficacy of rituximab. Accordingly, the Efficacy and Safety of Rituximab in Refractory CIDP Patients with IgG4 Autoantibodies trial, a prospective trial investigating the efficacy and safety of rituximab, is currently in progress.

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Remarkable Rituximab Response on Tremor Related to Acute‐Onset Chronic Inflammatory Demyelinating Polyradiculoneuropathy in an Antineurofascin155 Immunoglobulin G4–Seropositive Patient

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Cited by 8 publications

References 7 publications

Antibodies against the node of Ranvier: a real-life evaluation of incidence, clinical features and response to treatment based on a prospective analysis of 1500 sera

Antibodies against the node of Ranvier: a real-life evaluation of incidence, clinical features and response to treatment based on a prospective analysis of 1500 sera

Immunoadsorption and Plasma Exchange in Seropositive and Seronegative Immune-Mediated Neuropathies

Treatment of chronic inflammatory demyelinating polyradiculoneuropathy patients with antibodies against paranodal proteins

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