Analysis of auto-antibodies in psychotic disorder

OBJECTIVES: Antibodies against neuronal antigens such as N-methyl-D-aspartate receptor (NMDAr), and voltage gated potassium channel (VGKC) complexare present in various CNS excitability disorders, including cerebellar ataxia, encephalitis and epilepsy. Recently, an increasing number of reports indicatethat these types of antibodies are also seen in a subgroup of psychotic disorder patients. Yet, results of different research groups are inconsistent.We aimed to identify the presence of pathogenic autoantibodies targeting NMDAr and VGKC in sera of psychotic disorder and healthy individuals. METHODS: We analyzed the presence of NMDAr-autoantibodies of the IgG isotype in sera of 230 psychotic disorder patients and 293 controls. To this end we made use of an in-house cell based assay with HEK293 cells expressing GluN1 and GluN2B subunit of NMDAr. 120 schizophrenia patient sera were additionally screened for the presence of VGKC antibodies usingradio immuno assay (RIA) from DLDDiagnostika GmbH. Sera tested positive by RIA were subsequently retested with rat brain immunohistochemistry (IHC) and on cell based assay (CBA) of transfected HEK293 cells for the VGKC complex proteins leucine-rich glioma inactivated-1 (LGI-1) and contactin-associated protein-like 2 (CASPR2). RESULTS: No antibodies against the Nr1 subunit of the NMDAr were found in the sera of patients and controls. 4 patients were positive (>100 pmol/l) and 2 borderline positive (>50 pmol/l) for VGKC complex autoantibodies when tested by RIA. None of the positive screened sera could be confirmed as positive on rat brain IHC or CBA for CASPR2 and LGI-1. CONCLUSION: The results indicate that the presence of NMDAr-autoantibodies against Nr1 in the sera of patients with psychotic disorder is rare. Yet, we cannot rule out that these antibodies can only be detected in the cerebrospinal fluid of these patients.Autoantibodies against VGKC complex might be present in a small population of psychotic disorder patients. It has to be further investigated whether the indirect immunofluorescence is sensitive enough to detect autoantibodies in the serum or if the RIA could give false positive results.For a reliable diagnosis of patients it will be essential to improve the selectivity of the antibody detection assays as a solid basis for adequate immunosuppressive therapy.status: publishe

CD28-mediated costimulation impacts on the differentiation of DC vaccination-induced T cell responses

Costimulatory signals such as the ones elicited by CD28/B7 receptor ligation are essential for efficient T cell activation but their role in anti-tumour immune responses remains controversial. In the present study we compared the efficacy of DC vaccination-induced melanoma specific T cell responses to control the development of subcutaneous tumours and pulmonary metastases in CD28-deficient mice. Lack of CD28-mediated costimulatory signals accelerated tumour development in both model systems and also the load of pulmonary metastases was strongly increased by the end of the observation period. To scrutinize whether lack of CD28 signalling influences priming, homing or effector function of Trp-2(180−188)/K(b)-reactive T cells we investigated the characteristics of circulating and tumour infiltrating T cells. No difference in the frequency of Trp-2(180−188)/K(b)-reactive CD8(+) T cells could be demonstrated among the cellular infiltrate of subcutaneous tumours after DC vaccination between both genotypes. However, the number of IFN-γ-producing Trp-2-reactive cells was substantially lower in CD28-deficient mice and also their cytotoxicity was reduced. This suggests that CD28-mediated costimulatory signals are essential for differentiation of functional tumour-specific CD8(+) T-effector cells despite having no impact on the homing of primed CD8(+) T cells

Clinical relevance of distinguishing autoimmune nodopathies from CIDP:longitudinal assessment in a large cohort

Background: The aim of this study was to determine treatment response and whether it is associated with antibody titre change in patients with autoimmune nodopathy (AN) previously diagnosed as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and to compare clinical features and treatment response between AN and CIDP. Methods: Serum IgG antibodies to neurofascin-155 (NF155), contactin-1 (CNTN1) and contactin-associated protein 1 (CASPR1) were detected with cell-based assays in patients diagnosed with CIDP. Clinical improvement was determined using the modified Rankin scale, need for alternative and/or additional treatments and assessment of the treating neurologist. Results: We studied 401 patients diagnosed with CIDP and identified 21 patients with AN (10 anti-NF155, 6 anti-CNTN1, 4 anti-CASPR1 and 1 anti-NF155/anti-CASPR1 double positive). In patients with AN ataxia (68% vs 28%, p=0.001), cranial nerve involvement (34% vs 11%, p=0.012) and autonomic symptoms (47% vs 22%, p=0.025) were more frequently reported; patients with AN improved less often after intravenous immunoglobulin treatment (39% vs 80%, p=0.002) and required additional/alternative treatments more frequently (84% vs 34%, p&lt;0.001), compared with patients with CIDP. Antibody titres decreased or became negative in patients improving on treatment. Treatment withdrawal was associated with a titre increase and clinical deterioration in four patients. Conclusions: Distinguishing CIDP from AN is important, as patients with AN need a different treatment approach. Improvement and relapses were associated with changes in antibody titres, supporting the pathogenicity of these antibodies.</p