IgG4 anti-neurofascin155 antibodies in chronic inflammatory demyelinating polyradiculoneuropathy: Clinical significance and diagnostic utility of a conventional assay

Kadoya, Masato; Kaida, Kenichi; Koike, Haruki; Takazaki, Hiroshi; Ogata, Hidenori; Moriguchi, Kota; Shimizu, Jun; Nagata, Eiichiro; Takizawa, Shunya; Chiba, Atsuro; Yamasaki, Ryo; Kira, Jun Ichi; Sobue, Gen; Ikewaki, Katsunori

doi:10.1016/j.jneuroim.2016.10.013

Cited by 76 publications

(144 citation statements)

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“…As the space between myelin terminal loops and axolemma became wide in our cases, it may induce nerve conduction abnormalities that fulfil the electrodiagnostic criteria for CIDP. As IgG subclass of anti-neurofascin-155 and anti-contactin-1 antibodies was predominantly IgG4 that does not activate complement,22 it may therefore not initiate an inflammatory response. The absence of macrophage-mediated demyelination was the characteristic feature in patients with anti-neurofascin-155 and anti-contactin-1 antibodies.…”

Section: Discussionmentioning

confidence: 99%

“…All patients fulfilled definite electrodiagnostic criteria. The pathological features of these patients have not been reported elsewhere, whereas information on their clinical features was incorporated into another study analysing a larger series of patients 22. Administration of corticosteroids had been initiated in Patients 4 and 8, and IVIg had been given to Patient 7, prior to sural nerve biopsy.…”

Section: Methodsmentioning

confidence: 99%

“…22 Briefly, patient sera diluted at 1:200 with 1% bovine serum albumin in phosphate-buffered saline were used as primary antibodies. Horseradish peroxidase-conjugated anti-human IgG-Fc antibody (MP Biomedicals, Solon, USA) diluted at 1:500 with 1% bovine serum albumin in phosphate-buffered saline was used as the secondary antibody, and then a chromogenic reaction with O-phenylenediamine in phosphate–citrate buffer was developed.…”

Section: Methodsmentioning

confidence: 99%

“…22 Briefly, patient sera diluted at 1:200 with blocking buffer were used as primary antibodies, and horseradish peroxidase-conjugated anti-human IgG-Fc antibody diluted at 1:5000 with blocking buffer was used as the secondary antibody. The results were also verified by cell-based assay as previously described (see online supplementary data 1).…”

Section: Methodsmentioning

confidence: 99%

“…As the IgG subclass of autoantibodies in our patients was predominantly IgG4,22 we used sheep polyclonal antibody to IgG4 (The Binding Site Group, Birmingham, UK) and rabbit polyclonal antibody to contactin-associated protein (Caspr) (Abcam, Cambridge, UK) as primary antibodies to detect the deposition of autoantibodies. Rabbit monoclonal antibody to complement component 3d (C3d) (Abcam, Cambridge, UK) and sheep monoclonal antibody to IgG4 were used as primary antibodies to evaluate the deposition of complements.…”

Section: Methodsmentioning

confidence: 99%

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Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies

Koike

Kadoya

Kaida

et al. 2017

J Neurol Neurosurg Psychiatry

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ObjectiveTo investigate the morphological features of chronic inflammatory demyelinating polyneuropathy (CIDP) with autoantibodies directed against paranodal junctional molecules, particularly focusing on the fine structures of the paranodes.MethodsWe assessed sural nerve biopsy specimens obtained from 9 patients with CIDP with anti-neurofascin-155 antibodies and 1 patient with anti-contactin-1 antibodies. 13 patients with CIDP without these antibodies were also examined to compare pathological findings.ResultsCharacteristic light and electron microscopy findings in transverse sections from patients with anti-neurofascin-155 and anti-contactin-1 antibodies indicated a slight reduction in myelinated fibre density, with scattered myelin ovoids, and the absence of macrophage-mediated demyelination or onion bulbs. Teased-fibre preparations revealed that segmental demyelination tended to be found in patients with relatively higher frequencies of axonal degeneration and was tandemly found at consecutive nodes of Ranvier in a single fibre. Assessment of longitudinal sections by electron microscopy revealed that detachment of terminal myelin loops from the axolemma was frequently found at the paranode in patients with anti-neurofascin-155 and anti-contactin-1 antibody-positive CIDP compared with patients with antibody-negative CIDP. Patients with anti-neurofascin-155 antibodies showed a positive correlation between the frequencies of axo–glial detachment at the paranode and axonal degeneration, as assessed by teased-fibre preparations (p<0.05).ConclusionsParanodal dissection without classical macrophage-mediated demyelination is the characteristic feature of patients with CIDP with autoantibodies to paranodal axo–glial junctional molecules.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies

Koike

Kadoya

Kaida

et al. 2017

J Neurol Neurosurg Psychiatry

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169

198

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Intrathecal cytokine profile in neuropathy with anti‐neurofascin 155 antibody

Ogata

Yamasaki

et al. 2019

Ann Clin Transl Neurol

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authors are contributed equally to this manuscript. AbstractObjective: To characterize the CSF cytokine profile in chronic inflammatory demyelinating polyneuropathy (CIDP) patients with IgG4 anti-neurofascin 155 (NF155) antibodies (NF155 + CIDP) or those lacking anti-NF155 antibodies (NF155 À CIDP). Methods: Twenty-eight CSF cytokines/chemokines/growth factors were measured by multiplexed fluorescent immunoassay in 35 patients with NF155 + CIDP, 36 with NF155 À CIDP, and 28 with non-inflammatory neurological disease (NIND). Results: CSF CXCL8/IL-8, IL-13, TNF-a, CCL11/ eotaxin, CCL2/MCP-1, and IFN-c were significantly higher, while IL-1b, IL-1ra, and G-CSF were lower, in NF155 + CIDP than in NIND. Compared with NF155 À CIDP, CXCL8/IL-8 and IL-13 were significantly higher, and IL-1b, IL-1ra, and IL-6 were lower, in NF155 + CIDP. CXCL8/IL-8, IL-13, CCL11/eotaxin, CXCL10/IP-10, CCL3/MIP-1a, CCL4/MIP-1b, and TNF-a levels were positively correlated with markedly elevated CSF protein, while IL-13, CCL11/eotaxin, and IL-17 levels were positively correlated with increased CSF cell counts. IL-13, CXCL8/IL-8, CCL4/MIP-1b, CCL3/MIP-1a, and CCL5/RANTES were decreased by combined immunotherapies in nine NF155 + CIDP patients examined longitudinally. By contrast, NF155 À CIDP had significantly increased IFNc compared with NIND, and exhibited positive correlations of IFN-c, CXCL10/ IP-10, and CXCL8/IL-8 with CSF protein. Canonical discriminant analysis of cytokines/chemokines revealed that NF155 + and NF155 À CIDP were separable, and that IL-4, IL-10, and IL-13 were the three most significant discriminators. Interpretation: Intrathecal upregulation of type 2 helper T (Th2) cell cytokines is characteristic of IgG4 NF155 + CIDP, while type 1 helper T cell cytokines are increased in CIDP regardless of the presence or absence of anti-NF155 antibodies, suggesting that overproduction of Th2 cell cytokines is unique to NF155 + CIDP.

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Clinical and diagnostic features of anti‐neurofascin‐155 antibody‐positive neuropathy in Han Chinese

Wang

Liu

et al. 2022

Ann Clin Transl Neurol

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Objective To investigate the clinical features of Han Chinese patients with anti‐neurofascin‐155 (NF155) antibody‐positive neuropathy. Methods We screened 194 patients with peripheral neuropathy for NF155 antibodies using a cell‐based assay (CBA) and teased‐fiber immunofluorescence assay. We summarized the clinical findings of seropositive patients. Results The sera from 17 patients reacted to human embryonic kidney 293 cells transfected with NF155. Eleven of these patients had the immunoglobulin G (IgG) 4 isotype, a younger onset age, tremor, higher levels of cerebrospinal fluid protein, a larger diameter of the lumbosacral nerve root on magnetic resonance imaging, and the distal demyelinating symmetric phenotype. Most patients responded to steroids and rituximab. For the remaining six seropositive patients in CBA, the predominant antibody isotype was IgG3, IgG1, or undetectable, and only one patient with IgG3 showed a positive result in the teased‐fiber immunofluorescence assay. These patients did not share the typical features displayed by patients with the IgG4 isotype. Interpretation In the Han Chinese population, a significant proportion of patients who fulfilled the criteria for chronic inflammatory demyelinating polyradiculoneuropathy diagnosis had anti‐NF155 IgG4 antibody‐positive neuropathy and displayed specific phenotypes. Ambiguous staining patterns may appear, and the potential for false positivity should be considered. For patients who presented with specific phenotypes, identifying antibodies and subtypes involved a significant laboratory workup.

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IgG4 anti-neurofascin155 antibodies in chronic inflammatory demyelinating polyradiculoneuropathy: Clinical significance and diagnostic utility of a conventional assay

Cited by 76 publications

References 12 publications

Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies

Paranodal dissection in chronic inflammatory demyelinating polyneuropathy with anti-neurofascin-155 and anti-contactin-1 antibodies

Intrathecal cytokine profile in neuropathy with anti‐neurofascin 155 antibody

Clinical and diagnostic features of anti‐neurofascin‐155 antibody‐positive neuropathy in Han Chinese

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