| 1. |
- Bejerot, Susanne, 1955-, et al.
(författare)
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Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits)
- 2023
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Ingår i: BMC Psychiatry. - : BioMed Central (BMC). - 1471-244X. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture.METHODS: A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research.DISCUSSION: This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma.TRIAL REGISTRATION: NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14th of October 2022.
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| 2. |
- Ekman, Diana, et al.
(författare)
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Stratified genetic analysis reveals sex differences in MPO-ANCA-associated vasculitis
- 2023
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Ingår i: Rheumatology. - : Oxford University Press. - 1462-0324 .- 1462-0332. ; 62:9, s. 3213-3218
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To identify and genetically characterize subgroups of patients with ANCA-associated vasculitides (AAV) based on sex and ANCA subtype. Methods: A previously established SNP dataset derived from DNA sequencing of 1853 genes and genotyping of 1088 Scandinavian cases with AAV and 1589 controls was stratified for sex and ANCA subtype and analysed for association with five top AAV SNPs. rs9274619, a lead variant at the HLA-DQB1/HLA-DQA2 locus previously associated with AAV positive for myeloperoxidase (MPO)-ANCA, was analysed for association with the cumulative disease involvement of ten different organ systems. Results: rs9274619 showed a significantly stronger association to MPO-ANCA-positive females than males [P = 2.0 × 10-4, OR = 2.3 (95% CI 1.5, 3.5)], whereas proteinase 3 (PR3)-ANCA-associated variants rs1042335, rs9277341 (HLA-DPB1/A1) and rs28929474 (SERPINA1) were equally associated with females and males with PR3-ANCA. In MPO-ANCA-positive cases, carriers of the rs9274619 risk allele were more prone to disease engagement of eyes [P = 0.021, OR = 11 (95% CI 2.2, 205)] but less prone to pulmonary involvement [P = 0.026, OR = 0.52 (95% CI 0.30, 0.92)]. Moreover, AAV with both MPO-ANCA and PR3-ANCA was associated with the PR3-ANCA lead SNP rs1042335 [P = 0.0015, OR = 0.091 (95% CI 0.0022, 0.55)] but not with rs9274619. Conclusions: Females and males with MPO-ANCA-positive AAV differ in genetic predisposition to disease, suggesting at least partially distinct disease mechanisms between the sexes. Double ANCA-positive AAV cases are genetically similar to PR3-ANCA-positive cases, providing clues to the clinical follow-up and treatment of these patients.
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| 3. |
- Säve-Söderbergh, Melle, et al.
(författare)
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Gastrointestinal illness linked to incidents in drinking water distribution networks in Sweden
- 2017
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Ingår i: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 122, s. 503-511
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Tidskriftsartikel (refereegranskat)abstract
- During recent years, knowledge gaps on drinking water-related gastrointestinal illness have been identified, especially for non-epidemic cases. Pathogen contamination of drinking water during distribution has been suggested to contribute to these cases, but the risk factors are not yet fully understood. During 2014–2015, we conducted an epidemiological study in five municipalities in Sweden, to assess whether incidents in the drinking water distribution system influence the risk of gastrointestinal illness. Telephone interviews were conducted in the affected areas and in reference areas 7–14 days after a reported incident. Symptoms of gastrointestinal illness occurring during the period were documented for each household member. The results showed a significantly elevated risk of vomiting and acute gastrointestinal illness (AGI) in the affected areas, compared to the reference areas (ORvom. = 2.0, 95% CI: 1.2–3.3; ORAGI = 1.9, 95% CI: 1.2–3.0). Certain conditions, or risk factors, during the incidents, such as sewage and drinking water pipelines at the same level in the trench, were associated with an elevated risk of AGI and vomiting. Safety measures taken during repair work, like flushing, were also associated with an elevated risk of AGI and vomiting. These results show that incidents in the drinking water distribution network contribute to endemic gastrointestinal illness, especially AGI and vomiting, and that external pathogen contamination of the drinking water is a likely cause of these cases of gastrointestinal illness. The results also indicate that safety measures used today may not be sufficient for eliminating the risk of gastrointestinal illness.
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| 4. |
- Söderbergh, Annika, et al.
(författare)
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Autoantibodies linked to autoimmune polyendocrine syndrome type I are prevalent in Down syndrome
- 2006
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 95:12, s. 1657-1660
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with Down syndrome are prone to autoimmune diseases which also occur in the recessive disease autoimmune polyendocrine syndrome type I (APS I). Since this disease is caused by mutations in the gene AIRE on chromosome 21, one might speculate that altered expression of AIRE contributes to autoimmune disease in Down syndrome. AIM: To study the prevalence of 11 well-defined autoantibodies, five of which are specific for APS I, associated with various manifestations of APS I in patients with Down syndrome. METHODS: Sera from 48 patients with Down syndrome were analysed. Autoantibodies against 21-hydroxylase, 17alpha-hydroxylase, side-chain cleavage enzyme, aromatic L-amino acid decarboxylase, cytochrome P4501A2, tyrosine hydroxylase, tryptophan hydroxylase, glutamic acid decarboxylase 65, tyrosine phosphatase IA-2 and transglutaminase were analysed using an immunoprecipitation assay, and thyroid peroxidase autoantibodies were measured using a haemagglutination assay. RESULTS: Seven of 48 patients had elevated titres of autoantibodies: one against 21-hydroxylase, three against aromatic L-amino acid decarboxylase, one against cytochrome P4501A2, one against glutamic acid decarboxylase 65 and one against tyrosine phosphatase IA-2. None of the patients had clinical or laboratory signs of disease coupled to the respective autoantibody. CONCLUSION: Four patients with Down syndrome had autoantibodies hitherto regarded as unique for APS I, which may suggest a dysregulation of AIRE.
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| 5. |
- Söderbergh, Annika
(författare)
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Organ-specific autoantibodies in Addison's disease and autoimmune polyendocrine syndrome type I
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Assessment of autoantibodies is a valuable tool in the diagnostic procedure of autoimmune diseases. The aim of this study was to investigate the prevalence of different autoantibodies and their associations with disease manifestations in patients with Addison's disease and autoimmune polyendocrine syndrome type I (APS I).Sera from 89 of 101 patients with Addison's disease identified 21-hydroxylase (21-OH) in Western blot and/or in an immunoprecipitation assay. A minority of the patients also had autoantibodies against 17α-hydroxylase and side-chain cleavage enzyme (SCC). A subgroup of 12 patients had high titers of autoantibodies against the APS I-specific autoantigen aromatic L-amino acid decarboxylase (AADC), but lacked other characteristics of APS I, implying a milder atypical form of APS I, or perhaps a distinct disease entity in these patients.Patients with APS I develop various autoantibodies against intracellular organ-specific key enzymes. Sera from 90 patients with APS I were investigated and in a multivariate logistic regression analysis autoantibodies against 21-OH, SCC, protein tyrosine phosphatase IA-2 (IA-2), tryptophan hydroxylase and glutamic acid decarboxylase 65 (GAD65) were found to be independent predictors for Addison's disease, hypogonadism, insulin-dependent diabetes mellitus, autoimmune hepatitis and intestinal dysfunction.Down syndrome is associated with an increased incidence of organ-specific autoimmune diseases. The AIRE gene, located on chromosome 21, is mutated in patients with APS I. In an attempt to determine whether a gene-dose effect could contribute to autoimmunity in Down syndrome, sera from 48 patients were investigated. Seven patients had significant autoantibody titers against AADC, cytochrome P4501A2, GAD65, IA-2, or 21-OH. None of the patients had the associated disease manifestation. The presence of APS I-specific autoantibodies in patients with Down syndrome may be partly due to a dysregulation of the AIRE gene.
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| 6. |
- Söderbergh, Annika, et al.
(författare)
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Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:2, s. 557-562
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of autoantibodies against nine intracellular enzyme autoantigens, namely 21-hydroxylase, side-chain cleavage enzyme (SCC), 17 alpha-hydroxylase, glutamic acid decarboxylase 65, aromatic L-amino acid decarboxylase, tyrosine phosphatase-like protein IA-2, tryptophan hydroxylase (TPH), tyrosine hydroxylase, cytochrome P450 1A2, and against the extracellular calcium-sensing receptor, was assessed in 90 patients with autoimmune polyendocrine syndrome type I. A multivariate logistic regression analysis was performed for the presence of autoantibodies as independent predictors for different disease manifestations. Reactivities against 21-hydroxylase and SCC were associated with Addison's disease with odds ratios (ORs) of 7.8 and 6.8, respectively. Hypogonadism was exclusively associated with autoantibodies against SCC with an OR of 12.5. Autoantibodies against tyrosine phosphatase-like protein IA-2 were associated with insulin-dependent diabetes mellitus with an OR of 14.9, but with low sensitivity. Reactivities against TPH and, surprisingly, glutamic acid decarboxylase 65, were associated with intestinal dysfunction, with ORs of 3.9 and 6.7, respectively. TPH reactivity was the best predictor for autoimmune hepatitis, with an OR of 27.0. Hypoparathyroidism was not associated with reactivity against any of the autoantigens tested. No reactivity against the calcium-sensing receptor was found. Analysis of autoantibodies in autoimmune polyendocrine syndrome type I patients is a useful tool for establishing autoimmune manifestations of the disease as well as providing diagnosis in patients with suspected disease.
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