PT  - JOURNAL ARTICLE
AU  - Torres-Vega, Estefanía
AU  - Mancheño, Nuria
AU  - Cebrián-Silla, Arantxa
AU  - Herranz-Pérez, Vicente
AU  - Chumillas, María J.
AU  - Moris, Germán
AU  - Joubert, Bastien
AU  - Honnorat, Jérôme
AU  - Sevilla, Teresa
AU  - Vílchez, Juan J.
AU  - Dalmau, Josep
AU  - Graus, Francesc
AU  - García-Verdugo, José Manuel
AU  - Bataller, Luis
TI  - Netrin-1 receptor antibodies in thymoma-associated neuromyotonia with myasthenia gravis
AID  - 10.1212/WNL.0000000000003778
DP  - 2017 Mar 28
TA  - Neurology
PG  - 1235--1242
VI  - 88
IP  - 13
4099  - http://n.neurology.org/content/88/13/1235.short
4100  - http://n.neurology.org/content/88/13/1235.full
SO  - Neurology2017 Mar 28; 88
AB  - 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%).Caspr2=contactin-associated protein-like 2; DCC=deleted in colorectal carcinoma; OR=odds ratio; PPV=positive predictive value; UNC5A=uncoordinated-5A