Dataset Information

DNA hydrolysing IgG catalytic antibodies: an emerging link between psychoses and autoimmunity.

ABSTRACT: It is not uncommon to observe autoimmune comorbidities in a significant subset of patients with psychotic disorders, namely schizophrenia (SCZ) and bipolar disorder (BPD). To understand the autoimmune basis, the DNA abyzme activity mediated by serum polyclonal IgG Abs were examined in psychoses patients, quantitatively, by an in-house optimized DNase assay. A similar activity exhibited by IgG Abs from neuropsychiatric-systemic lupus erythematosus (NP-SLE) patients was used as a comparator. Our data revealed that the IgG DNase activity of SCZ was close to that of NP-SLE and it was twofold higher than the healthy controls. Interestingly, the association between DNase activity with PANSS (positive, general and total scores) and MADRS were noted in a subgroup of SCZ and BPD patients, respectively. In our study group, the levels of IL-6 and total IgG in BPD patients were higher than SCZ and healthy controls, indicating a relatively inflammatory nature in BPD, while autoimmune comorbidity was mainly observed in SCZ patients.

SUBMITTER: Ramesh R

PROVIDER: S-EPMC7910540 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

DNA hydrolysing IgG catalytic antibodies: an emerging link between psychoses and autoimmunity.

Ramesh Rajendran R Sundaresh Aparna A Rajkumar Ravi Philip RP Negi Vir Singh VS Vijayalakshmi M A MA Krishnamoorthy Rajagopal R Tamouza Ryad R Leboyer Marion M Kamalanathan A S AS

NPJ schizophrenia 20210226 1

It is not uncommon to observe autoimmune comorbidities in a significant subset of patients with psychotic disorders, namely schizophrenia (SCZ) and bipolar disorder (BPD). To understand the autoimmune basis, the DNA abyzme activity mediated by serum polyclonal IgG Abs were examined in psychoses patients, quantitatively, by an in-house optimized DNase assay. A similar activity exhibited by IgG Abs from neuropsychiatric-systemic lupus erythematosus (NP-SLE) patients was used as a comparator. Our d ...[more]

PMID: 33637732

Similar Datasets

Project description:The prevalence of obesity has risen sharply in the United States in the past few decades. Etiologic links between obesity and substance use disorders have been hypothesized.To determine whether familial risk of alcohol dependence predicts obesity and whether any such association became stronger between the early 1990s and early 2000s.We conducted analyses of the repeated cross-sectional National Longitudinal Alcohol Epidemiologic Survey (1991-1992) and National Epidemiologic Survey on Alcohol and Related Conditions (2001-2002).The noninstitutionalized US adult population in 1991-1992 and 2001-2002.Individuals drawn from population-based, multistage, random samples (N = 39 312 and 39 625).Obesity, defined as a body mass index (calculated from self-reported data as weight in kilograms divided by height in meters squared) of 30 or higher and predicted from family history of alcoholism and/or problem drinking.In 2001-2002, women with a family history of alcoholism (defined as having a biological parent or sibling with a history of alcoholism or alcohol problems) had 49% higher odds of obesity than those without a family history (odds ratio, 1.48; 95% confidence interval, 1.36-1.61; P < .001), a highly significant increase (P < .001) from the odds ratio of 1.06 (95% confidence interval, 0.97-1.16) estimated for 1991-1992. For men in 2001-2002, the association was significant (odds ratio, 1.26; 95% confidence interval, 1.14-1.38; P < .001) but not as strong as for women. The association and the secular trend for women were robust after adjustment for covariates, including sociodemographic variables, smoking status, alcohol use, alcohol or drug dependence, and major depression. Similar trends were observed for men but did not meet statistical significance criteria after adjustment for covariates.These results provide epidemiologic support for a link between familial alcoholism risk and obesity in women and possibly in men. This link has emerged in recent years and may result from an interaction between a changing food environment and predisposition to alcoholism and related disorders.

Project description:Developmental biology has long been ignored in the etiology and diverse manifestations of autoimmune diseases. Yet a role for development is suggested by intriguing overlaps in particular organs targeted in autoimmune diseases, in this case type 1 diabetes and Sjogren's syndrome. Patients with type 1 diabetes have high rates of co-occurring Sjogren's syndrome, and both conditions are associated with hearing loss and tongue abnormalities. All of these co-occurrences are found in organs tracing their lineage to the developmental transcription factor Hox11, which is expressed in embryonic cells destined for the pancreas, salivary glands, tongue, cranial nerves and cochlea. To determine whether development contributes to autoimmunity, we compared four target organs in NOD mice (an animal model for type 1 diabetes and Sjogren's syndrome) with NOD-SCID mice (which lack lymphocytes) and normal controls. We examined the structure and/or function of the cochlea, salivary glands, pancreas and tongue at early time points after birth. Before the usual time of the onset of type 1 diabetes or Sjogren's syndrome, we show that all four Hox11-derived organs are structurally abnormal in both NOD mice and NOD-SCID mice versus controls. The most striking functional defect is near complete hearing loss occurring before the normal time of the onset of autoimmunity. The hearing loss is associated with severe structural defects in the cochlea, suggesting that near-deafness occurs independent of autoimmune attack. The pancreas and salivary glands are also structurally abnormal in NOD and NOD-SCID mice, but they are functionally normal. This suggests that autoimmune attack of these two organs is required for functional failure. We conclude that a developmental lineage of cells contributes to autoimmunity and predicts which organs may be targeted, either structurally and/or functionally. Taken together, our findings challenge the orthodoxy that autoimmunity is solely caused by a defective immune system.

Project description:ObjectiveTo describe a novel antibody biomarker of neurologic paraneoplastic autoimmunity specific for phosphodiesterase 10A (PDE10A), a striatum-enriched phosphodiesterase, and to characterize the clinical phenotype of patients with PDE10A immunoglobulin G (IgG).MethodsWe describe 7 patients with autoantibodies specific for PDE10A identified in the Mayo Clinic Neuroimmunology Laboratory. Patient specimens (sera, 7; CSF, 4) produced identical basal ganglia-predominant synaptic staining of murine brain tissue by indirect immunofluorescence. The autoantigen was identified by immunoprecipitation and mass spectrometry as PDE10A, and confirmed by antigen-specific recombinant Western blot and cell-based assays, and immune absorption experiments.ResultsThe median patient age was 70 years (range 66-76); 4 were men. Four patients with clinical information available had movement disorders (hyperkinetic in 3 [chorea, ballismus, dystonia] and parkinsonism in 1). All patients but one had cancer (lung [adenocarcinoma 1, squamous cell carcinoma 1, poorly differentiated mesenchymal carcinoma 1], renal adenocarcinoma 2, and pancreatic adenocarcinoma 1). Two of the 7 patients developed hyperkinetic movement disorders during treatment with immune checkpoint inhibitors (nivolumab and pembrolizumab), though none of 26 cancer control patients treated with immune checkpoint inhibitors harbored PDE10A IgG in their serum. MRIs from those 2 patients with hyperkinetic movement disorders demonstrated fluid-attenuated inversion recovery/T2 basal ganglia hyperintensities, and their CSF harbored unique oligoclonal bands. One of those 2 patients had substantial improvement after corticosteroids. One patient's renal adenocarcinoma expressed PDE10A by immunohistochemistry.ConclusionsPDE10A IgG defines a novel rare neurologic autoimmune syndrome and expands the spectrum of diagnosable paraneoplastic CNS disorders. The intracellular location of PDE10A suggests a T-cell-mediated pathology targeting cells displaying MHC1-bound PDE10A peptides.

Dataset Information

DNA hydrolysing IgG catalytic antibodies: an emerging link between psychoses and autoimmunity.

Publications

DNA hydrolysing IgG catalytic antibodies: an emerging link between psychoses and autoimmunity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets