Deleted in colorectal cancer (netrin-1 receptor) antibodies and limbic encephalitis in a cat with hippocampal necrosis

Hasegawa, Daisuke; Ohnishi, Yumi; Koyama, Eiji; Matsunaga, Satoru; Ohtani, Shouhei; Nakanishi, Akio; Shiga, Takanori; Chambers, James K.; Uchida, Kazuyuki; Yokoi, Norihiko; Fukata, Yuko; Fukata, Masaki

Eleven cases of feline LE associated with VGKC complex/LGI1 antibody were treated successfully with immunosuppressive doses of corticosteroids. 5, 6 In the case presented here, we did not suspect LE at first diagnosis, so the cat was treated with medium to low doses of prednisolone (0.5-1.0 mg/kg) for 2 weeks for treatment of brain edema (hippocampal swelling). During prednisolone treatment, seizures were well controlled and other clinical signs also improved. Generally, in human medicine, paraneoplastic LEs have poor response to immunosuppressive treatment, whereas non-paraneoplastic LEs show comparatively good response. 11 In addition, it is also described that human patients with paraneoplastic epilepsy are poorly responsive to antiepileptic drugs and require earlier treatment for underlying tumors. 13 We could not define whether the present cat was paraneoplastic or non-paraneoplastic, whether it was associated with DCC antibodies only or whether there was coexistence of multiple antibodies, and whether F I G U R E 5 Immunoprecipitation of the cell surface target protein with cat serum antibodies. The immunoprecipitates of serum antibodies bound to rat hippocampal neurons were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with silver staining (upper). The specific band at 190 kDa (an arrow) was analyzed by mass spectral analysis. The immunoprecipitates were analyzed by Western blotting (lower) with anti-deleted in colorectal carcinoma (DCC) mouse monoclonal antibody. A dot observed between healthy cat #2 and epileptic cat #1 lanes is a nonspecific signal. IgG, immunoglobulin heavy chain. Input: cell extract from which immunoprecipitation was performed. See also the Supporting Information F I G U R E 6 The case cat serum antibodies bound to the COS7 cells expressing deleted in colorectal carcinoma (DCC). COS7 cells were transfected to surface-express DCC. Transfected cells were fixed and doubly stained with the serum immunoglobulin G (IgGs) (right column, red) together with an antibody to DCC (left column, green). Note that the case cat serum antibodies, neither healthy nor epileptic control cats serum antibodies, specifically bind to DCCexpressing cells. Human neuromyotonia (NMT) patient serum was used as a positive control (tops). The slight dot-like signals observed in cat IgG (right panels) is noisy background, which was observed in all cat serum IgG, irrespective of transfected cells. Scale bar, 20 μm. See also the Supporting Information DCC antibodies were the underlying cause of the epilepsy. Diagnoses of these factors could possibly provide more appropriate therapeutic regimen for cats with LE.