Targeted immunotherapy with rituximab leads to a transient alteration of the IgG autoantibody profile in pemphigus vulgaris.

In pemphigus vulgaris (PV), IgG autoantibodies against the ectodomain of desmoglein 3 (Dsg3) have been shown to be directly responsible for the loss of keratinocyteadhesion. The aim of the present study was to study the effect of the B cell depleting anti-CD20 monoclonal antibody, rituximab, on the profile of pathogenic IgG against distinct regions of the Dsg3 ectodomain in 22 PV patients who were followed up clinically and serologically by Dsg3 ELISA over 12-24 months. Prior to rituximab, all the 22 PV patients showed IgG against Dsg3 (Dsc3EC1-5). Specifically, 14/22 showed IgG reactivity against the Dsg3EC1 subdomain, 5/22 patients against Dsg3EC2, 7/22 against Dsg3EC3, 11/22 against Dsg3EC4, and 2/22 against Dsg3EC5. Within 6 months after rituximab, all the patients showed significant clinical improvement and reduced IgG against Dsg3 (5/22) and the various subdomains, that is, Dsg3EC1 (7/22), Dsg3EC2 (3/22), Dsg3EC3 (2/22), sg3EC4 (2/22), and Dsg3EC5 (0/22). During the entire observation period, 6/22 PV patients experienced a clinical relapse which was associated with the reappearance of IgG against previously recognized Dsg3 subdomains, particularly against the Dsg3EC1. Thus, in PV, rituximab only temporarily depletes pathogenic B cell responses against distinct subdomains of Dsg3 which reappear upon clinical relapse.

Limbic system abnormalities associated with Ammon's horn sclerosis do not alter seizure outcome after amygdalohippocampectomy.

PURPOSE: To evaluate whether limbic system abnormalities associated with Ammon's horn sclerosis alter seizure outcome after selective amgydalohippocampectomy. METHODS: In 45 patients with unilateral mesial temporal lobe epilepsy, histologically proven Ammon's horn sclerosis, and uneventful postoperative course, volumes of the hippocampus, hemisphere, amygdala, entorhinal cortex, mamillary body, and fornix were measured by using a T(1)-weighted 3-D gradient-echo sequence with roughly isotropic (1.17 x 1.17 x 1-mm) voxels. In addition, signal intensity of the hippocampus and of the temporal lobe white matter was visually assessed and graded on a coronal T(2)-weighted fast-spin-echo sequence with 2-mm-thick slices. Volumetric measurements and visual analysis were compared between seizure-free and non-seizure-free patients examined 12 months after surgery. RESULTS: Hippocampal, hemispheric, entorhinal cortex, mamillary body, and fornix volumes, but not amygdalar volumes, were significantly smaller on the operated-on than on the non-operated-on side and significantly smaller in patients compared with controls. No volume differences of the hippocampus, hemisphere, amygdala, entorhinal cortex, mamillary body, and fornix existed between seizure-free (Engel class IA) and non-seizure-free patients (Engel class IB-IV). Increased temporal lobe white matter signal was observed in 15 patients but did not alter seizure outcome. CONCLUSIONS: Limbic system abnormalities are not a surrogate marker to predict postsurgical seizure outcome in patients with unilateral Ammon's horn sclerosis.