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Neurology. 2017 Mar 28;88(13):1235-1242. doi: 10.1212/WNL.0000000000003778. Epub 2017 Mar 1.

Netrin-1 receptor antibodies in thymoma-associated neuromyotonia with myasthenia gravis.

Author information

1
From the Laboratorio de Neurología (E.T.-V., T.S., J.J.V., L.B.), Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe, CIBERER, Valencia; Servicio de Anatomía Patológica (N.M.), Servicio de Neurofisiología Clínica (M.J.C.), and Servicio de Neurología (T.S., J.J.V., L.B.), Hospital Universitario y Politécnico La Fe, Valencia; Laboratorio de Neurobiología Comparada (A.C.-S., V.H.-P., J.M.G.-V.), Instituto Cavanilles, Universidad de Valencia, CIBERNED; Servicio de Neurología (G.M.), Hospital Central de Asturias, Oviedo, Spain; French Reference Center on Paraneoplastic Neurological Syndrome (B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron, and Institut NeuroMyoGene INSERM U1217/CNRS UMR 5310, Université de Lyon-Université Claude Bernard Lyon 1, France; Laboratori de Neurologia (J.D., F.G.), Institut d´Investigacions Biomèdiques August Pi I Sunyer, CIBERER, Barcelona, Spain; and Department of Neurology (J.D.), University of Pennsylvania, Philadelphia, and Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
2
From the Laboratorio de Neurología (E.T.-V., T.S., J.J.V., L.B.), Instituto de Investigación Sanitaria La Fe, Hospital Universitario y Politécnico La Fe, CIBERER, Valencia; Servicio de Anatomía Patológica (N.M.), Servicio de Neurofisiología Clínica (M.J.C.), and Servicio de Neurología (T.S., J.J.V., L.B.), Hospital Universitario y Politécnico La Fe, Valencia; Laboratorio de Neurobiología Comparada (A.C.-S., V.H.-P., J.M.G.-V.), Instituto Cavanilles, Universidad de Valencia, CIBERNED; Servicio de Neurología (G.M.), Hospital Central de Asturias, Oviedo, Spain; French Reference Center on Paraneoplastic Neurological Syndrome (B.J., J.H.), Hospices Civils de Lyon, Hôpital Neurologique, Bron, and Institut NeuroMyoGene INSERM U1217/CNRS UMR 5310, Université de Lyon-Université Claude Bernard Lyon 1, France; Laboratori de Neurologia (J.D., F.G.), Institut d´Investigacions Biomèdiques August Pi I Sunyer, CIBERER, Barcelona, Spain; and Department of Neurology (J.D.), University of Pennsylvania, Philadelphia, and Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain. bataller_lui@gva.es.

Abstract

OBJECTIVE:

To identify cell-surface antibodies in patients with neuromyotonia and to describe the main clinical implications.

METHODS:

Sera of 3 patients with thymoma-associated neuromyotonia and myasthenia gravis were used to immunoprecipitate and characterize neuronal cell-surface antigens using reported techniques. The clinical significance of antibodies against precipitated proteins was assessed with sera of 98 patients (neuromyotonia 46, myasthenia gravis 52, thymoma 42; 33 of them with overlapping syndromes) and 219 controls (other neurologic diseases, cancer, and healthy volunteers).

RESULTS:

Immunoprecipitation studies identified 3 targets, including the Netrin-1 receptors DCC (deleted in colorectal carcinoma) and UNC5A (uncoordinated-5A) as well as Caspr2 (contactin-associated protein-like 2). Cell-based assays with these antigens showed that among the indicated patients, 9 had antibodies against Netrin-1 receptors (7 with additional Caspr2 antibodies) and 5 had isolated Caspr2 antibodies. Only one of the 219 controls had isolated Caspr2 antibodies with relapsing myelitis episodes. Among patients with neuromyotonia and/or myasthenia gravis, the presence of Netrin-1 receptor or Caspr2 antibodies predicted thymoma (p < 0.05). Coexisting Caspr2 and Netrin-1 receptor antibodies were associated with concurrent thymoma, myasthenia gravis, and neuromyotonia, often with Morvan syndrome (p = 0.009). Expression of DCC, UNC5A, and Caspr2 proteins was demonstrated in paraffin-embedded thymoma samples (3) and normal thymus.

CONCLUSIONS:

Antibodies against Netrin-1 receptors (DCC and UNC5a) and Caspr2 often coexist and associate with thymoma in patients with neuromyotonia and myasthenia gravis.

CLASSIFICATION OF EVIDENCE:

This study provides Class III evidence that antibodies against Netrin-1 receptors can identify patients with thymoma (sensitivity 21.4%, specificity 100%).

PMID:
28251919
PMCID:
PMC5373776
DOI:
10.1212/WNL.0000000000003778
[Indexed for MEDLINE]
Free PMC Article

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