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Autoantibody profiles associated with clinical features in psychotic disorders.

ABSTRACT: Autoimmune processes are suspected to play a role in the pathophysiology of psychotic disorders. Better understanding of the associations between auto-immunoglobulin G (IgG) repertoires and clinical features of mental illness could yield novel models of the pathophysiology of psychosis, and markers for biological patient stratification. We undertook cross-sectional detection and quantification of auto-IgGs in peripheral blood plasma of 461 people (39% females) with established psychotic disorder diagnoses. Broad screening of 24 individuals was carried out on group level in eight clinically defined groups using planar protein microarrays containing 42,100 human antigens representing 18,914 proteins. Autoantibodies indicated by broad screening and in the previous literature were measured using a 380-plex bead-based array for autoantibody profiling of all 461 individuals. Associations between autoantibody profiles and dichotomized clinical characteristics were assessed using a stepwise selection procedure. Broad screening and follow-up targeted analyses revealed highly individual autoantibody profiles. Females, and people with family histories of obesity or of psychiatric disorders other than schizophrenia had the highest overall autoantibody counts. People who had experienced subjective thought disorder and/or were treated with clozapine (trend) had the lowest overall counts. Furthermore, six autoantibodies were associated with specific psychopathology symptoms: anti-AP3B2 (persecutory delusions), anti-TDO2 (hallucinations), anti-CRYGN (initial insomnia); anti-APMAP (poor appetite), anti-OLFM1 (above-median cognitive function), and anti-WHAMMP3 (anhedonia and dysphoria). Future studies should clarify whether there are causal biological relationships, and whether autoantibodies could be used as clinical markers to inform diagnostic patient stratification and choice of treatment.

SUBMITTER: Jernbom Falk A

PROVIDER: S-EPMC8438048 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We previously reported a contemporaneous onset of cancer and scleroderma in patients with anti-RNA polymerase III antibodies, and we identified a biologic link between cancer and scleroderma. This investigation was designed to further evaluate whether autoantibody status and other characteristics are associated with cancer and a clustering of cancer with scleroderma onset.Logistic regression analysis was performed to assess the relationship of 2 outcomes, cancer (model 1) and a short (±2 years) cancer-scleroderma interval (model 2), with autoantibody status and scleroderma covariates.Of 1,044 scleroderma patients, 168 (16.1%) had cancer. In the adjusted model 1, only older age at scleroderma onset (odds ratio 1.04 [95% confidence interval 1.02-1.05]) and white race (odds ratio 2.71 [95% confidence interval 1.22-6.04]) were significantly associated with an increased overall risk of cancer. In the adjusted model 2, only anti-RNA polymerase III positivity (odds ratio 5.08 [95% confidence interval 1.60-16.1]) and older age at scleroderma onset (odds ratio 1.04 [95% confidence interval 1.00-1.08]) were significantly associated with a short cancer-scleroderma interval. While anti-RNA polymerase III positivity was associated with a short cancer-scleroderma interval independent of age at scleroderma onset, the cancer-scleroderma interval shortened with older age at scleroderma onset in other antibody groups (Spearman's correlation P < 0.05), particularly among patients with anti-topoisomerase I antibodies and patients who were negative for anticentromere, anti-topoisomerase I, and anti-RNA polymerase III antibodies.Increased age at scleroderma onset is strongly associated with cancer risk overall. While anti-RNA polymerase III status is an independent marker of coincident cancer and scleroderma at any age, a clustering of cancer with scleroderma is also seen in patients with anti-topoisomerase I and other autoantibody specificities who develop scleroderma at older ages.

Project description:BackgroundSystemic sclerosis (SSc) belongs to the group of connective tissue diseases and is associated with the occurrence of disease-specific autoantibodies. Although it is still controversial whether these antibodies contribute to pathogenesis, there are new insights into the development of these specific antibodies and their possible pathophysiological properties. Interestingly, they are associated with specific clinical manifestations, but for some rarer antibodies this association is not fully clarified. The aim of this study is a comprehensive analysis of the serum autoantibody status in patients with SSc followed by correlation analyses of autoantibodies with the clinical course of the disease.MethodsSerum from SSc patients was analyzed using a line blot (EUROLINE, EUROIMMUN AG) for SSc-related autoantibodies. Autoantibodies to centromere, Topo-1, antimitochondrial antibodies (AMA) M2 subunit, angiotensin II type 1 receptors (AT1R) and endothelin-1 type-A-receptors (ETAR) were also determined by ELISA. We formed immunological clusters and used principal components analysis (PCA) to assign specific clinical characteristics to these clusters.ResultsA total of 372 SSc patients were included. 95.3% of the patients were antinuclear antibody positive and in 333 patients at least one SSc specific antibody could be detected. Four immunological clusters could be found by PCA. Centromere, Topo-1 and RP3 all formed own clusters, which are associated with distinct clinical phenotypes. We found that patients with an inverted phenotype, such as limited cutaneous SSc patients within the Topo-1 cluster show an increased risk for interstital lung disease compared to ACA positive patients. Anti-AT1R and anti-ETAR autoantibodies were measured in 176 SSc patients; no association with SSc disease manifestation was found. SSc patients with AMA-M2 antibodies showed an increased risk of cardiovascular events.ConclusionIn our in large cluster analysis, which included an extended autoantibody profile, we were able to show that serologic status of SSc patients provides important clues to disease manifestation, co-morbidities and complications. Line blot was a reliable technique to detect autoantibodies in SSc and detected rarer autoantibodies in 42% of our patients.

Project description:Objective: To analyze the positive and recurrence rates of different autoantibody-associated demyelination disorders in children in Southwest China, and describe the clinical, radiological, and prognostic features of the myelin oligodendrocyte glycoprotein antibody (MOG-ab) and aquaporin-4 antibody (AQP4-ab) associated disease. This study also summarizes steroid maintenance therapy approaches for MOG-ab-positive children. Methods: A total of 160 children presenting with acquired demyelinating syndromes (ADS) between January 2016 and December 2019 were tested for MOG-ab and AQP4-ab. Clinical data, MRI scans, and survival analyses were compared between MOG-ab-positive and AQP4-ab-positive children. Evolution of serologic status and treatment response to immunosuppressants were collected in MOG-ab-positive children. Results: Of the 160 included children, the MOG-ab positivity rate (47.4%) was significantly higher than the AQP4-ab (5%) positivity rate. The recurrence rate for AQP4-ab disease (71.4%) was higher than that of MOG-ab disease (30.1%). For 135 children with both MOG-ab and AQP4-ab tested, the median age at onset was 7 (interquartile range [IQR] 5-10) years, and the median follow-up period was 19 (IQR 13-27.5) months. MOG-ab-positive children more frequently presented with acute disseminated encephalomyelitis, had deep gray matter lesions on MRI, had a better clinical and radiological recovery, and were less likely to have sustained disability than AQP4-ab-positive children. In MOG-ab-positive and AQP4-ab-positive children, maintenance therapy was a protective factor for recurrence, but presenting optic neuritis was a predictor of earlier relapse. A high Expanded Disability Status Scale score at onset was associated with sustained disability. Steroid maintenance therapy longer than 6 months after the initial attack was associated with a lower risk of a second relapse in MOG-ab-positive children. On serial serum MOG antibody analysis, clinical relapse occurred in 34.6% of children with persistent seropositivity, but none of the children who converted to seronegative status experienced relapse. Conclusion: The MOG antibody is more common in children with ADS than the AQP4 antibody. MOG-ab-positive children are characterized by distinct clinical and radiological features. Although some MOG-ab-positive children experience relapsing courses or have persistently seropositive status, they still predict a better outcome than AQP4-ab-positive children.

Project description:BackgroundPsychotic major depression (PMD) is a subtype of depression with a poor prognosis. Previous studies have failed to find many differences between patients with PMD and those with non-psychotic major depression (NMD) or schizophrenia (SZ). We compared sociodemographic factors (including season of conception) and clinical characteristics between patients with PMD, NMD, and schizophrenia. Our aim was to provide data to help inform clinical diagnoses and future etiology research.MethodsThis study used data of all patients admitted to Shandong Mental Health Center from June 1, 2016 to December 31, 2017. We analyzed cases who had experienced an episode of PMD (International Classification of Diseases, Tenth Revision codes F32.3, F33.3), NMD (F32.0-2/9, F33.0-2/9), and SZ (F20-20.9). Data on sex, main discharge diagnosis, date of birth, ethnicity, family history of psychiatric diseases, marital status, age at first onset, education, allergy history, and presence of trigger events were collected. Odds ratios (OR) were calculated using logistic regression analyses. Missing values were filled using the k-nearest neighbor method.ResultsPMD patients were more likely to have a family history of psychiatric diseases in their first-, second-, and third-degree relatives ([OR] 1.701, 95% confidence interval [CI] 1.019-2.804) and to have obtained a higher level of education (OR 1.451, 95% CI 1.168-1.808) compared with depression patients without psychotic features. Compared to PMD patients, schizophrenia patients had lower education (OR 0.604, 95% CI 0.492-0.741), were more often divorced (OR 3.087, 95% CI 1.168-10.096), had a younger age of onset (OR 0.934, 95% CI 0.914-0.954), less likely to have a history of allergies (OR 0.604, 95% CI 0.492-0.741), and less likely to have experienced a trigger event 1 year before first onset (OR 0.420, 95% CI 0.267-0.661). Season of conception, ethnicity, and sex did not differ significantly between PMD and NMD or schizophrenia and PMD.ConclusionsPMD patients have more similarities with NMD patients than SZ patients in terms of demographic and clinical characteristics. The differences found between PMD and SZ, and PMD and NMD correlated with specificity of the diseases. Furthermore, allergy history should be considered in future epidemiological studies of psychotic disorders.

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Autoantibody profiles associated with clinical features in psychotic disorders.

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