Autoantibodies against glutamate receptor δ2 after allogenic stem cell transplantation

Objective: To report on a Caucasian patient who developed steroid-responsive transverse myelitis, graft vs host disease of the gut, and anti-GluR delta 2 after allogenic stem cell transplantation. Methods: Histoimmunoprecipitation (HIP) with the patient's serum and cryosections of rat and porcine cerebellum followed by mass spectrometry was used to identify the autoantigen. Correct identification was verified by indirect immunofluorescence using recombinant GluR delta 2 expressed in HEK293 cells. Results: The patient's serum produced a granular staining of the cerebellar molecular layer (immunoglobulin G1 and immunoglobulin G3; endpoint titer: 1:1,000) but did not react with other CNS tissues or 28 established recombinant neural autoantigens. HIP revealed a unique protein band at; 110 kDa that was identified as GluR delta 2. The patient's serum also stained GluR delta 2 transfected but not mock-transfected HEK293 cells. Control sera from 38 patients with multiple sclerosis, 85 patients with other neural autoantibodies, and 205 healthy blood donors were negative for anti-GluR delta 2. Preadsorption with lysate from HEK293-GluR delta 2 neutralized the patient's tissue reaction whereas control lysate had no effect. In addition to anti-GluR delta 2, the patient's serum contained immunoglobulin G autoantibodies against the pancreatic glycoprotein CUZD1, which are known to be markers of Crohn disease. Conclusions: In the present case, the development of anti-GluR delta 2 was associated with transverse myelitis, which was supposedly triggered by the stem cell transplantation. Similar to encephalitis in conjunction with anti-GluR delta 2 reported in a few Japanese patients, the patient's neurologic symptoms ameliorated after steroid therapy.