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- Gerhards, R, et al.
(författare)
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Oligodendrocyte myelin glycoprotein as a novel target for pathogenic autoimmunity in the CNS
- 2020
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Ingår i: Acta neuropathologica communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 8:1, s. 207-
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune disorders of the central nervous system (CNS) comprise a broad spectrum of clinical entities. The stratification of patients based on the recognized autoantigen is of great importance for therapy optimization and for concepts of pathogenicity, but for most of these patients, the actual target of their autoimmune response is unknown. Here we investigated oligodendrocyte myelin glycoprotein (OMGP) as autoimmune target, because OMGP is expressed specifically in the CNS and there on oligodendrocytes and neurons. Using a stringent cell-based assay, we detected autoantibodies to OMGP in serum of 8/352 patients with multiple sclerosis, 1/28 children with acute disseminated encephalomyelitis and unexpectedly, also in one patient with psychosis, but in none of 114 healthy controls. Since OMGP is GPI-anchored, we validated its recognition also in GPI-anchored form. The autoantibodies to OMGP were largely IgG1 with a contribution of IgG4, indicating cognate T cell help. We found high levels of soluble OMGP in human spinal fluid, presumably due to shedding of the GPI-linked OMGP. Analyzing the pathogenic relevance of autoimmunity to OMGP in an animal model, we found that OMGP-specific T cells induce a novel type of experimental autoimmune encephalomyelitis dominated by meningitis above the cortical convexities. This unusual localization may be directed by intrathecal uptake and presentation of OMGP by meningeal phagocytes. Together, OMGP-directed autoimmunity provides a new element of heterogeneity, helping to improve the stratification of patients for diagnostic and therapeutic purposes.
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- Uriarte, SA, et al.
(författare)
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Clinical and Immunologic Changes due to Subcutaneous Immunotherapy With Cat and Dog Extracts Using an Ultrarush Up-Dosing Phase: A Real-Life Study
- 2022
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Ingår i: Journal of investigational allergology & clinical immunology. - : Esmon Publicidad, SA. - 1018-9068. ; 32:2, s. 133-
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We aimed to evaluate the efficacy of and immunologic changes caused by subcutaneous immunotherapy (SCIT) in patients with allergy to cat and dog. Methods: The study population comprised patients with rhinitis and/or asthma and allergy to cat or dog from a previous safety study. All patients had specific IgE to cat and/or dog. The SCIT maintenance dose was administered using an infusion pump over a single 4-hour session, followed by monthly administration over 6 months. Data were gathered on clinical outcomes, pulmonary function, FeNO, rhinitis and asthma symptoms, quality of life (QOL), and scores for the Asthma Control Test and symptom visual analog scale were recorded at baseline and then at 1, 3, and 6 months. Specific IgE and IgG antibody responses to cat and dog allergens were determined. Results: The study population comprised 61 patients with a mean age of 35.6 (9.7) years, of whom 40 underwent SCIT for at allergy. A significant improvement was observed in rhinitis and asthma symptoms and in QOL, use of medication, visual analog scale score, and Asthma Control Test score at 1 month; these improvements persisted at month 6. The clinical improvement with cat extract was significantly more marked than with dog extract. Nearly half of the patients (49.09%) had an increase of >0.9 in the ESPRINT-15 QOL in allergic rhinitis questionnaire, and 58.18% had an increase of >0.5 in the Asthma Quality of Life Questionnaire score at month 6. Both differences represent the minimal clinical important difference. A significant increase was observed in specific IgG and IgE to different allergens at 3 and/or 6 months. Conclusions: Ultrarush SCIT with cat and dog extracts has substantial clinical value for many patients.
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- Bedri, SK, et al.
(författare)
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From Genetic Variations to Biomarkers
- 2014
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Ingår i: SCANDINAVIAN JOURNAL OF IMMUNOLOGY. - 0300-9475. ; 79:6, s. 477-477
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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- Wang, Rui, et al.
(författare)
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Mixed brain lesions mediate the association between cardiovascular risk burden and cognitive decline in old age : A population-based study
- 2017
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 13:3, s. 247-256
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The underlying pathological mechanisms linking cardiovascular burden to cognitive decline remain unclear. Methods: We investigated the associations of the Framingham general cardiovascular risk score (FGCRS), apolipoprotein E (APOE) 64, and brain structure with the Mini-Mental State Examination (MMSE) decline using the 9-year follow-up data from Swedish National Study on Aging and Care in Kungsholmen (n = 2189, age >= 60) and the embedded magnetic resonance imaging (MRI) (n = 448) studies. Volumes of white matter hyperintensities (WMHs), total gray matter, ventricles, and hippo campus were assessed in the MRI sample. Results: A higher FGCRS was associated with faster MMSE decline in young-old people (60-72 years) but not in old-old (>= 78 years). Larger volumes of cerebral WMHs and ventricles and smaller volumes of total gray matter and hippocampus were all associated with accelerated MMSE decline (P <.01); these associations were stronger among APOE epsilon 4 carriers than noncarriers. Simultaneously entering multiple brain lesion markers as mediators in the model substantially attenuated the association between FGCRS and MMSE decline. Discussion: The effect of cardiovascular risk burden on cognitive deterioration in old age is largely mediated by mixed brain lesions.
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- Zhang, Y, et al.
(författare)
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Medial temporal lobe atrophy increases the specificity of cerebrospinal fluid biomarkers in Alzheimer disease with minor cerebrovascular changes.
- 2009
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 1600-0455 .- 0284-1851. ; 50:6, s. 674-81
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although cerebrospinal fluid (CSF) biomarkers and medial temporal lobe atrophy (MTA) contribute to the diagnosis of Alzheimer disease (AD), they may not be specific. Relatively little is known about how they correlate with each other. PURPOSE: To identify the validity of the radiological linear measurements of brain atrophy in AD diagnosis by examining the correlation with CSF biomarkers and by examining if specificity could be improved in classification of AD from controls, when the linear measurements are combined with the CSF biomarkers. MATERIAL AND METHODS: 59 controls (20 male/39 female, age 73+/-8 years), 162 pure AD patients (49/113, 74+/-7 years), and 86 AD patients with minor cerebrovascular changes (CVC) (31/55, 77+/-5 years), aged between 52 and 94 years, were recruited from the Malmo Alzheimer Study. AD patients were subgrouped into "pure AD" and "AD + CVC" in order to clarify the possible influence of CVC on atrophy or CSF biomarkers in AD patients. Abeta42, T-tau, and P-tau in CSF were examined. Computed tomography (CT) linear measurements were performed, which included temporal horn ratio and suprasellar cistern ratio that reflect MTA. RESULTS: Compared with the 14 significant correlations between the CT measurements and three CSF biomarkers in the pure AD group, there was only one significant correlation in the AD + CVC group and one in the control group. In particular, P-tau correlates with temporal horn ratio only in pure AD. When the CT measurements were added with CSF biomarkers as independent variables in discriminant analysis, the percentage of correct classification of AD + CVC from controls increased from 79.5% (only CSF biomarkers) to 84.6% (combined CT measurements with CSF biomarkers). However, little was changed in the pure AD group. CONCLUSION: P-tau correlates with the linear CT measure of MTA only in pure AD without CVC. Combined with the measure of MTA, the specificity of CSF biomarkers can be increased, but only in AD + CVC. The linear measurements of MTA are of value in AD diagnosis.
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