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RESEARCH PRODUCT

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

José Manuel García-verdugoGermán MorísJérôme HonnoratNuria MancheñoBastien JoubertMaría José ChumillasJuan J. VílchezVicente Herranz-perezLuis BatallerJosep DalmauTeresa SevillaFrancesc GrausArantxa Cebrián-sillaEstefanía Torres-vega

subject

0301 basic medicineAdultMaleThymomaNeuromyotoniaDeleted in Colorectal CancerThymomaCell Adhesion Molecules NeuronalNerve Tissue ProteinsReceptors Cell SurfaceTransfectionArticle03 medical and health sciences0302 clinical medicineAntigenMyasthenia GravismedicineHumansImmunoprecipitationNerve Growth FactorsReceptorMuscle SkeletalNeural Cell Adhesion MoleculesAgedAutoantibodiesbiologybusiness.industryElectromyographyTumor Suppressor ProteinsCalcium-Binding ProteinsAutoantibodyMembrane ProteinsThymus NeoplasmsMiddle AgedNetrin-1medicine.diseaseDCC ReceptorMagnetic Resonance ImagingMyasthenia gravis030104 developmental biologyHEK293 CellsImmunologybiology.proteinFemaleNeurology (clinical)AntibodybusinessNetrin Receptors030217 neurology & neurosurgery

description

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%).

10.1212/wnl.0000000000003778https://pubmed.ncbi.nlm.nih.gov/28251919