| 1. |
- Brozzetti, A, et al.
(författare)
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Autoantibody response against NALP5/MATER in primary ovarian insufficiency and in autoimmune Addison's disease
- 2015
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 100:5, s. 1941-1948
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Tidskriftsartikel (refereegranskat)abstract
- Context:NACHT leucine-rich-repeat protein 5 (NALP5)/maternal antigen that embryo requires (MATER) is an autoantigen in hypoparathyroidism associated with autoimmune polyendocrine syndrome type 1 (APS1) but is also expressed in the ovary. Mater is an autoantigen in experimental autoimmune oophoritis.Objectives:The objectives of the study were to determine the frequency of NALP5/MATER autoantibodies (NALP5/MATER-Ab) in women with premature ovarian insufficiency (POI) and in patients with autoimmune Addison's disease (AAD) and to evaluate whether inhibin chains are a target for autoantibodies in POI.Methods:Autoantibodies against NALP5/MATER and inhibin chains-α and -βA were determined by radiobinding assays in 172 patients with AAD without clinical signs of gonadal insufficiency, 41 women with both AAD and autoimmune POI [steroidogenic cell autoimmune POI (SCA-POI)], 119 women with idiopathic POI, 19 patients with APS1, and 211 healthy control subjects.Results:NALP5/MATER-Ab were detected in 11 of 19 (58%) sera from APS1 patients, 12 of 172 (7%) AAD sera, 5 of 41 (12%) SCA-POI sera, 0 of 119 idiopathic POI sera and 1 of 211 healthy control sera (P < .001). None of 160 POI sera, including 41 sera from women with SCA-POI and 119 women with idiopathic POI, and none of 211 healthy control sera were positive for inhibin chain-α/βA autoantibodies.Conclusions:NALP5/MATER-Ab are associated with hypoparathyroidism in APS1 but are present also in patients with AAD and in women with SCA-POI without hypoparathyroidism. Inhibin chains do not appear to be likely candidate targets of autoantibodies in human POI.
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| 2. |
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| 3. |
- Albrecht, Inka, et al.
(författare)
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Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies
- 2015
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Ingår i: Journal of Clinical Investigation. - : AMER SOC CLINICAL INVESTIGATION INC. - 0021-9738 .- 1558-8238. ; 125:12, s. 4612-4624
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Tidskriftsartikel (refereegranskat)abstract
- Mutations of the gene encoding four-and-a-half LIM domain 1 (FHL1) are the causative factor of several X-linked hereditary myopathies that are collectively termed FHL1-related myopathies. These disorders are characterized by severe muscle dysfunction and damage. Here, we have shown that patients with idiopathic inflammatory myopathies (IIMs) develop autoimmunity to FHL1, which is a muscle-specific protein. Anti-FHL1 autoantibodies were detected in 25% of IIM patients, while patients with other autoimmune diseases or muscular dystrophies were largely anti-FHL1 negative. Anti-FHL1 reactivity was predictive for muscle atrophy, dysphagia, pronounced muscle fiber damage, and vasculitis. FHL1 showed an altered expression pattern, with focal accumulation in the muscle fibers of autoantibody-positive patients compared with a homogeneous expression in anti-FHL1-negative patients and healthy controls. We determined that FHL1 is a target of the cytotoxic protease granzyme B, indicating that the generation of FHL1 fragments may initiate FHL1 autoimmunity. Moreover, immunization of myositis-prone mice with FHL1 aggravated muscle weakness and increased mortality, suggesting a direct link between anti-FHL1 responses and muscle damage. Together, our findings provide evidence that FHL1 may be involved in the pathogenesis not only of genetic FHL1-related myopathies but also of autoimmune IIM. Importantly, these results indicate that anti-FHL1 autoantibodies in peripheral blood have promising potential as a biomarker to identify a subset of severe IIM.
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| 4. |
- Andersson, A, et al.
(författare)
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White spot lesion regression with the CPP-ACP system assessed by a laser fluorescence device (DIAGNOdent).
- 2006
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Ingår i: Oral Health Prev Dent.
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate and compare the effects of a dental cream containing complexes of casein phosphoprotein-amorphous calcium phosphate (CPP-ACP) and fluoride mouth rinses on the regression of white spot lesions (WSL). Material and methods: The study group consisted of 26 healthy adolescents (mean age 14.6 yr) exhibiting 60 teeth with 152 visible WSL sites on incisors and canines immediately after debonding of fixed orthodontic appliances. After bracket removal, professional tooth cleaning and drying, a visual scoring (0-4) and laser fluorescence (LF) readings were carried out. The patients were randomly assigned to two different treatment protocols with the aim to remineralize the lesions: A) daily topical applications of a dental cream containing CPP-ACP (Topacal) for 3 months followed by a 3-month period of daily tooth brushing with fluoridated toothpaste, or B) daily 0.05% sodium fluoride rinses combined with fluoridated toothpaste for 6 months. The registrations were repeated after 1, 3, 6 and 12 months and follow-up data were compared with baseline with aid of chi-square and paired t-tests. Results: A significant improvement of the clinical WSL-scores was found over time in both groups but there was a statistically significant difference (p<0.01) concerning the number of sites that totally disappeared after 12 months in favor for the CPP-ACP regime, 63% vs. 25% respectively. The clinical registrations were mirrored by a statistically significant decrease (p<0.05) in the LF readings at the 6- and 12-month follow-ups compared to baseline. No significant differences were displayed between the groups. Conclusion: Clinical scoring and LF assessment suggested that both regimens could promote regression of WSL after debonding of fixed orthodontic appliances. The visual evaluation suggested an aesthetically more favourable outcome of the amorphous calcium phosphate treatments.
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| 5. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 6. |
- Ernsth Bravell, Marie, et al.
(författare)
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Motor functioning differentially predicts mortality in men and women
- 2017
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Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier. - 0167-4943 .- 1872-6976. ; 72, s. 6-11
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionResearch indicates gender differences in functional performance at advanced ages, but little is known about their impact on longevity for men and women.ObjectiveTo derive a set of motor function factors from a battery of functional performance measures and examine their associations with mortality, incorporating possible gender interactions.MethodAnalyses were performed on the longitudinal Swedish Adoption/Twin Study of Aging (SATSA) including twenty-four assessments of motor function up to six times over a 19-year period. Three motor factors were derived from several factor analyses; fine motor, balance/upper strength, and flexibility. A latent growth curve model was used to capture longitudinal age changes in the motor factors and generated estimates of intercept at age 70 (I), rates of change before (S1) and after age 70 (S2) for each factor. Cox regression models were used to determine how gender in interaction with the motor factors was related to mortality.ResultsFemales demonstrated lower functional performance in all motor functions relative to men. Cox regression survival analyses demonstrated that both balance/upper strength, and fine motor function were significantly related to mortality. Gender specific analyses revealed that this was true for women only. For men, none of the motor factors were related to mortality.ConclusionWomen demonstrated more difficulties in all functioning facets, and only among women were motor functioning (balance/upper strength and fine motor function) associated with mortality. These results provide evidence for the importance of considering motor functioning, and foremost observed gender differences when planning for individualized treatment and rehabilitation.
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| 7. |
- Hallgren, Jenny, 1978-, et al.
(författare)
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Factors associated with hospitalization risk among community living middle aged and older persons : Results from the Swedish Adoption/Twin Study of Aging (SATSA)
- 2016
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Ingår i: Archives of gerontology and geriatrics (Print). - : Elsevier. - 0167-4943 .- 1872-6976. ; 66, s. 102-108
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Tidskriftsartikel (refereegranskat)abstract
- The aims of the present study were to: (1) describe and compare individual characteristics of hospitalized and not hospitalized community living persons, and (2) to determine factors that are associated with hospitalization risk over time. We conducted a prospective study with a multifactorial approach based on the population-based longitudinal Swedish Adoption/Twin Study of Aging (SATSA). A total of 772 Swedes (mean age at baseline 69.7 years, range 46–103, 59.8% females) answered a postal questionnaire about physical and psychological health, personality and socioeconomic factors. During nine years of follow-up, information on hospitalizations and associated diagnoses were obtained from national registers. Results show that 484 persons (63%) had at least one hospital admission during the follow-up period. The most common causes of admission were cardiovascular diseases (25%) and tumors (22%). Cox proportional hazard regression models controlling for age, sex and dependency within twin pairs, showed that higher age (HR = 1.02, p < 0.001) and more support from relatives (HR = 1.09, p = 0.028) were associated with increased risk of hospitalization, while marital status (unmarried (HR = 0.75, p = 0.033) and widow/widower (HR = 0.69, p < 0.001)) and support from friends (HR = 0.93, p = 0.029) were associated with lower risk of hospitalization. Social factors were important for hospitalization risk even when medical factors were controlled for in the analyses. Number of diseases was not a risk in the final regression model. Hospitalization risk was also different for women and men and within different age groups. We believe that these results might be used in future interventions targeting health care utilization.
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| 8. |
- Aranda-Guillén, Maribel, et al.
(författare)
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A polygenic risk score to help discriminate primary adrenal insufficiency of different etiologies.
- 2023
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Ingår i: Journal of internal medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 294:1, s. 96-109
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune Addison's disease (AAD) is the most common cause of primary adrenal insufficiency (PAI). Despite its exceptionally high heritability, tools to estimate disease susceptibility in individual patients are lacking. We hypothesized that polygenic risk score (PRS) for AAD could help investigate PAI pathogenesis in pediatric patients.We here constructed and evaluated a PRS for AAD in 1223 seropositive cases and 4097 controls. To test its clinical utility, we reevaluated 18 pediatric patients, whose whole genome we also sequenced. We next explored the individual PRS in more than 120 seronegative patients with idiopathic PAI.The genetic susceptibility to AAD-quantified using PRS-was on average 1.5 standard deviations (SD) higher in patients compared with healthy controls (p < 2e - 16), and 1.2 SD higher in the young patients compared with the old (p = 3e - 4). Using the novel PRS, we searched for pediatric patients with strikingly low AAD susceptibility and identified cases of monogenic PAI, previously misdiagnosed as AAD. By stratifying seronegative adult patients by autoimmune comorbidities and disease duration we could delineate subgroups of PRS suggesting various disease etiologies.The PRS performed well for case-control differentiation and susceptibility estimation in individual patients. Remarkably, a PRS for AAD holds promise as a means to detect disease etiologies other than autoimmunity.
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| 9. |
- Alvarado-Vazquez, Perla A., et al.
(författare)
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Use of spirometry-like measurements to monitor house dust mite-induced experimental asthma in mice
- 2021
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:7, s. 2204-2207
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Tidskriftsartikel (refereegranskat)abstract
- Weight and age correlated positively with FEV 0.1 and PEF among other lung function parameters in naïve mice. Lung function parameters decline in a model of experimental asthma induced by intranasal HDM administrations. Systemic injections of dexamethasone improved lung function, decreased mast cell populations and BAL levels of mast cell protease-1 in the HDM model.
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| 10. |
- Cardenas, Eduardo, I, et al.
(författare)
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Elastase- and LPS-Exposed Cpa3(Cre/+) and ST2(-/-) Mice Develop Unimpaired Obstructive Pulmonary Disease
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- IL-33 and its receptor ST2, as well as mast cells and their mediators, have been implicated in the development of chronic obstructive pulmonary disease (COPD). However, whether mast cells and the ST2 receptor play a critical role in COPD pathophysiology remains unclear. Here, we performed repeated intranasal administrations of porcine pancreatic elastase and LPS for four weeks to study COPD-like disease in wildtype, ST2-deficient, and Cpa3(Cre/+) mice, which lack mast cells and have a partial reduction in basophils. Alveolar enlargement and changes in spirometry-like parameters, e.g. increased dynamic compliance and decreased expiratory capacity, were evident one day after the final LPS challenge and worsened over time. The elastase/LPS model also induced mild COPD-like airway inflammation, which encompassed a transient increase in lung mast cell progenitors, but not in mature mast cells. While ST2-deficient and Cpa3(Cre/+) mice developed reduced pulmonary function uninterruptedly, they had a defective inflammatory response. Importantly, both ST2-deficient and Cpa3(Cre/+) mice had fewer alveolar macrophages, known effector cells in COPD. Elastase/LPS instillation in vivo also caused increased bronchiole contraction in precision cut lung slices challenged with methacholine ex vivo, which occurred in a mast cell-independent fashion. Taken together, our data suggest that the ST2 receptor and mast cells play a minor role in COPD pathophysiology by sustaining alveolar macrophages.
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