Autoantibody pathogenicity in a multifocal motor neuropathy induced pluripotent stem cell–derived model

Harschnitz, Oliver; Berg, Leonard H van den; Johansen, Lill Eva; Jansen, Marc; Kling, Sandra; Sá, Renata Vieira de; Vlam, Lotte; Rheenen, Wouter van; Karst, H.; Wierenga, Corette J.; Pasterkamp, R. Jeroen; Pol, W. Ludo van der

doi:10.1002/ana.24680

Cited by 63 publications

(72 citation statements)

References 58 publications

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“…Indeed, non-myelinating cultures of iPSC-derived motor neurons have recently been used to study the immunopathology of multifocal motor neuropathy associated anti-GM1 antibodies (Harschnitz et al , 2016). Dysimmune processes underlying other inflammatory neuropathies are known to target distinct topographical regions of the peripheral nerve, including the myelin sheath and specialized axonal domains formed at the node of Ranvier and flanking paranodal and juxtaparanodal domains (Devaux et al , 2012; Querol et al , 2013).…”

Section: Discussionmentioning

confidence: 99%

Co-cultures with stem cell-derived human sensory neurons reveal regulators of peripheral myelination

Clark

Kaller

Galino

et al. 2017

Brain

101

112

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See Saporta and Shy (doi:) for a scientific commentary on this article.Clark et al. report that human sensory neurons derived from iPSCs can be myelinated by rat Schwann cells in culture. Such co-cultures develop features of mature myelinated fibres in a neuregulin-1 dependent manner. Antiganglioside antibodies associated with inflammatory peripheral neuropathies can both impede myelination and cause loss of established myelin.

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Section: Discussionmentioning

confidence: 99%

Co-cultures with stem cell-derived human sensory neurons reveal regulators of peripheral myelination

Clark

Kaller

Galino

et al. 2017

Brain

101

112

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“…MMN is an immune‐mediated, pure motor neuropathy characterized by slowly progressive, typically asymmetric weakness of the limbs . The characteristic EDX criteria for MMN are conduction block outside common sites of entrapment and normal sensory studies .…”

Section: Sonographic Abnormalities In Polyneuropathiesmentioning

confidence: 99%

Nerve ultrasound in polyneuropathies

et al. 2018

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Ultrasound can be used to visualize pathology in the peripheral nerves of patients with polyneuropathy. Nerve enlargement is the most frequent pathology, but other abnormalities, including abnormal nerve echogenicity and vascularity, are also encountered. This monograph presents an overview of the role of nerve ultrasound in the evaluation and management of both inherited and acquired polyneuropathies. A description of the sonographic techniques and common abnormalities is provided, followed by a presentation of typical findings in different neuropathies. Scoring systems for characterizing the presence and pattern of nerve abnormalities as they relate to different polyneuropathies are presented. Muscle Nerve 57: 716-728, 2018.

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“…Despite major sequence homology, interspecies variability may be relevant enough to hinder novel antigen identification. Thus, exploring novel viable sources of obtaining differentiated human neural cells would greatly benefit the search of new antigens, as has been proven in nonparaneoplastic autoimmune neuropathies 45, 46. Another limitation in our study includes the lack of identification of antigens of lipidic or glucidic nature.…”

Section: Discussionmentioning

confidence: 98%

Antibodies against cell adhesion molecules and neural structures in paraneoplastic neuropathies

Siles

Martínez‐Hernández

Araque

et al. 2018

Ann Clin Transl Neurol

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ObjectiveParaneoplastic neurological syndromes (PNS) are rare neurological disorders in which ectopic expression of neural antigens by a tumor results in an autoimmune attack against the nervous system. Onconeural antibodies not only guide PNS diagnosis but may also help detecting underlying malignancies. Our project aims to uncover new potential antibodies in paraneoplastic neuropathies (PN).MethodsThirty‐four patients fulfilling diagnostic criteria of possible (n = 9; 26.5%) and definite (n = 25; 73.5%) PN without onconeural antibodies and 28 healthy controls were included in our study. Sera were tested for known antibodies against neural cell adhesion molecules and screened for novel IgG and IgM reactivities against nerve components: dorsal root ganglia (DRG) neurons, motor neurons, and Schwann cells. Patients showing autoantibodies against any of these cell types were used for immunoprecipitation (IP) studies.ResultsOverall, 9 (26.5%) patients showed significant reactivity against DRG neurons, motor neurons, or Schwann cells, whereas 5 (17.9%) healthy controls only showed moderate reactivity. Compared with control sera, serum samples from patients with paraneoplastic sensory‐motor neuropathies had a higher frequency of IgM antibodies against Schwann cells (0% vs. 40%; P = 0.0028). No novel antigens were identified from our IP experiments. Antibodies against the neural adhesion molecules CNTN1, NF155, NF140, NF186, NCAM1, L1CAM, and the CNTN1/CASPR1 complex were not detected in patients with PN. One (2.9%) patient with CIDP and thymoma had CASPR2 antibodies.InterpretationAlmost 30% of patients with PN harbor antibodies targeting neural structures, suggesting that novel neoplasm‐associated antigens remain to be discovered.

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Autoantibody pathogenicity in a multifocal motor neuropathy induced pluripotent stem cell–derived model

Cited by 63 publications

References 58 publications

Co-cultures with stem cell-derived human sensory neurons reveal regulators of peripheral myelination

Co-cultures with stem cell-derived human sensory neurons reveal regulators of peripheral myelination

Nerve ultrasound in polyneuropathies

Antibodies against cell adhesion molecules and neural structures in paraneoplastic neuropathies

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