| 1. |
- Agarwal, Pallavi, et al.
(författare)
-
Enhanced deposition of cartilage oligomeric matrix protein is a common feature in fibrotic skin pathologies
- 2013
-
Ingår i: Matrix Biology. - : Elsevier BV. - 1569-1802 .- 0945-053X. ; 32:6, s. 325-331
-
Tidskriftsartikel (refereegranskat)abstract
- Skin fibrosis is characterized by activated fibroblasts and an altered architecture of the extracellular matrix. Excessive deposition of extracellular matrix proteins and altered cytokine levels in the dermal collagen matrix are common to several pathological situations such as localized scleroderma and systemic sclerosis, keloids, dermatosclerosis associated with venous ulcers and the fibroproliferative tissue surrounding invasively growing tumors. Which factors contribute to altered organization of dermal collagen matrix in skin fibrosis is not well understood. We recently demonstrated that cartilage oligomeric matrix protein (COMP) functions as organizer of the dermal collagen I network in healthy human skin (Agarwal et al., 2012). Here we show that COMP deposition is enhanced in the dermis in various fibrotic conditions. COMP levels were significantly increased in fibrotic lesions derived from patients with localized scleroderma, in wound tissue and exudates of patients with venous leg ulcers and in the fibrotic stroma of biopsies from patients with basal cell carcinoma. We postulate enhanced deposition of COMP as one of the common factors altering the supramolecular architecture of collagen matrix in fibrotic skin pathologies. Interestingly, COMP remained nearly undetectable in normally healing wounds where myofibroblasts transiently accumulate in the granulation tissue. We conclude that COMP expression is restricted to a fibroblast differentiation state not identical to myofibroblasts which is induced by TGF beta and biomechanical forces. (C) 2013 Elsevier B.V. All rights reserved.
|
|
| 2. |
- Andraos, Rama, et al.
(författare)
-
Autoantibodies associated with systemic sclerosis in three autoimmune diseases imprinted by type I interferon gene dysregulation: a comparison across SLE, primary Sjogrens syndrome and systemic sclerosis
- 2022
-
Ingår i: Lupus Science and Medicine. - : BMJ PUBLISHING GROUP. - 2053-8790. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveSLE, primary Sjogrens syndrome (pSS) and systemic sclerosis (SSc) are heterogeneous autoimmune diseases with a dysregulated type I interferon (IFN) system. The diseases often show overlapping clinical manifestations, which may result in diagnostic challenges. We asked to which extent SSc-associated autoantibodies are present in SLE and pSS, and whether these link to serum IFN-alpha, clinical phenotypes and sex. Samples with clinical data from patients with SSc and healthy blood donors (HBDs) served as controls. Finally, the diagnostic performance of SSc-associated autoantibodies was evaluated.MethodsSamples from well-characterised subjects with SLE (n=510), pSS (n=116), SSc (n=57) and HBDs (n=236) were analysed using a commercially available immunoassay (EuroLine Systemic Sclerosis Profile (IgG)). IFN-alpha was quantified by ELISA. Self-reported data on Raynauds phenomenon (RP) were available.ResultsWith exceptions for anti-Ro52/SSA and anti-Th/To, SSc-associated autoantibodies were more frequent in SSc than in SLE, pSS and HBDs regardless of sex. IFN-alpha levels correlated with the number of positive SSc-associated autoantibodies (r=0.29, p<0.0001) and associated with Ro52/SSA positivity (p<0.0001). By using data from SLE, SSc and HBDs, RP was significantly associated with topoisomerase I, centromere protein (CENP)-B, RNA polymerase III 11 kDa, RNA polymerase III 155 kDa and PM-Scl100 whereas Ro52/SSA associated inversely with RP. In SLE, CENP-A was associated with immunological disorder, CENP-B with serositis and Ku with lupus nephritis. By combining analysis of ANA (immunofluorescence) with SSc-associated autoantibodies, the diagnostic sensitivity reached 98% and the specificity 33%.ConclusionsThe 13 specificities included in the EuroLine immunoassay are commonly detected in SSc, but they are also frequent among individuals with other diseases imprinted by type I IFNs. These findings are valuable when interpreting serological data on patients with suspected SSc, especially as patients may present with disease manifestations overlapping different rheumatological diseases. In SLE, we observed associations between manifestations and SSc-associated autoantibodies which have not previously been reported.
|
|
| 3. |
- Andréasson, Kristofer, et al.
(författare)
-
Cartilage oligomeric matrix protein: a new promising biomarker of liver fibrosis in chronic hepatitis C
- 2015
-
Ingår i: Infectious Diseases. - : Informa UK Limited. - 2374-4243 .- 2374-4235. ; 47:12, s. 915-918
-
Tidskriftsartikel (refereegranskat)abstract
- Cartilage oligomeric matrix protein (COMP) is a biomarker of fibrosis in lung and skin. In this exploratory study we investigated the biomarker potential of COMP in chronic hepatitis C (CHC). We included consecutive patients with CHC admitted to the Department of Infectious Diseases, Lund University Hospital. COMP was analysed in serum using ELISA. The correlations between COMP and liver fibrosis, determined by transient elastography (TE) (n = 47) and liver biopsy (n = 28) were assessed. We also studied COMP prospectively in relation to antiviral treatment (n = 10). COMP correlated with the degree of liver fibrosis as assessed by TE (r = 0.71, p < 0.001) and liver biopsy (r(s) = 0.65, p < 0.001). After successful treatment of CHC, COMP decreased from 18 to 13 U/l (p = 0.011). We suggest that COMP is associated with the stage of liver fibrosis in CHC. The biomarker potential of COMP in CHC warrants further investigation.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Andréasson, Kristofer, et al.
(författare)
-
Disease Features and Gastrointestinal Microbial Composition in Patients with Systemic Sclerosis from Two Independent Cohorts
- 2022
-
Ingår i: ACR Open Rheumatology. - : Wiley. - 2578-5745. ; 4:5, s. 417-425
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The study objective was to examine alterations in gastrointestinal (GI) microbial composition in patients with systemic sclerosis (SSc) and to investigate the relationship between SSc features and GI microbiota using two independent, international cohorts. Methods: Prospective patients with SSc from Lund University (LU), Sweden, from the University of California, Los Angeles (UCLA), United States, and control subjects provided stool specimens for 16S ribosomal RNA sequencing. Alpha and beta diversity analyses were performed. Multivariate negative binomial models identified differentially abundant genera between groups. Results: Patients from LU with SSc (n = 106) with recent SSc diagnosis (median disease duration 2.0 years) had lower abundance of commensal genera (eg, Faecalibacterium) and higher abundance of pathobiont genera (eg, Desulfovibrio) than LU-controls (n = 85). Patients from UCLA with SSc (n = 71) had a similar prevalence of females, a similar body mass index, and similar age but an increased disease duration (median 7.1 years) compared with patients from LU with SSc. Factors associated with beta diversity in patients with SSc from both LU and UCLA included disease duration (P = 0.0016), interstitial lung disease (P = 0.003), small intestinal bacterial overgrowth (P = 0.002), and immunosuppression use (P = 0.014). In multivariable analysis, the UCLA-SSc cohort had higher abundance of specific pathobiont genera (eg, Streptococcus) compared with the LU-SSc cohort. Conclusion: Enrichments and depletions in certain microbial genera were observed in patients recently diagnosed with SSc, suggesting that dysbiosis is present in early SSc. Specific disease features were independently associated with fecal microbial composition in both cohorts. After controlling for these factors, the abundance of several pathobiont bacteria differed between the cohorts, suggesting that environmental factors, along with disease manifestations, should be considered in future SSc studies.
|
|
| 7. |
|
|
| 8. |
- Andréasson, Kristofer, et al.
(författare)
-
Faecal calprotectin: a biomarker of gastrointestinal disease in systemic sclerosis.
- 2011
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 270, s. 50-57
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract. Andréasson K, Scheja A, Saxne T, Ohlsson B, Hesselstrand R. (Section for Rheumatology; Section for Gastroenterology and Hepatology, Lund University, Lund, Sweden). Faecal calprotectin: a biomarker of gastrointestinal disease in systemic sclerosis. J Intern Med 2010; doi: 10.1111/j.1365-2796.2010.02340.x. Background. Assessment of gastrointestinal (GI) involvement in systemic sclerosis (SSc) is difficult. Measurement of calprotectin in faeces is a valuable tool for the assessment of inflammatory bowel diseases. Calprotectin is an intracellular protein found in leucocytes and is a potent activator of the innate immune system. Objective. To determine whether faecal calprotectin (F-calprotectin) could serve as a biomarker of GI disease in SSc. Design. In a cross-sectional study, F-calprotectin and plasma calprotectin were measured in patients with SSc using an enzyme-linked immunosorbent assay. F-calprotectin concentrations were evaluated in relation to cineradiography, medical records, laboratory measurements and patients' subjective GI symptoms. Setting. The study was conducted at a tertiary referral centre for SSc. Subjects. The study comprised 81 consecutive patients with SSc. Results. A majority of the patients had pathological levels of F-calprotectin when compared to accepted clinical reference values for healthy adults. F-calprotectin did not correlate with calprotectin levels in plasma. F-calprotectin was associated with the following patient characteristics: pathological cineradiography, history of referral to another clinic because of GI disease, treatment of vitamin or mineral deficiency and use of proton pump inhibitors. We did not find any significant correlation between F-calprotectin and patient-reported GI symptoms. Conclusion. Faecal calprotectin is increased in a majority of patients with SSc. It correlates with objective and clinically important features of GI disease, and faecal concentrations do not vary with plasma concentrations. We suggest that F-calprotectin is a promising objective non-invasive biomarker of GI involvement in SSc.
|
|
| 9. |
- Andréasson, Kristofer, et al.
(författare)
-
Faecal levels of calprotectin in systemic sclerosis are stable over time and are higher compared to primary Sjogren's syndrome and rheumatoid arthritis
- 2014
-
Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 16:1
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Faecal calprotectin (FC) has been proposed to be a biomarker of gastrointestinal (GI) disease in systemic sclerosis (SSc). The purpose of this study was to extend cross-sectional observations and prospectively assess the variability of FC over time in SSc patients. We also aimed to examine FC in relation to immunosuppressive therapy. Finally we wanted to analyse FC in other rheumatic diseases to evaluate the specificity of FC for SSc GI disease. Methods: FC was measured in consecutive patients with SSc, primary Sjogren's syndrome (pSS), rheumatoid arthritis (RA) and in healthy hospital workers. The intraindividual variability of FC in SSc was assessed with intra class correlation (ICC) and. statistics. Associations between FC and objective markers of GI disease and immunosuppressive medication were investigated. Results: FC was associated with micronutrient deficiency and GI pathology as assessed by cineradiography confirming our previous results. FC showed only a limited intra-individual variation in SSc, ICC = 0.69 (95% confidence interval, CI: 0.57-0.78) and kappa = 0.64 (95% CI: 0.56-0.73). Generalised immunosuppression did not have any significant impact on FC. FC was significantly higher in SSc patients compared to patients with pSS or RA as well as compared to healthy subjects. Conclusions: FC is a promising non-invasive biomarker for GI disease in SSc. In view of stable levels over time, FC could be a useful marker when novel, more specific drugs targeting the GI tract in SSc will be introduced.
|
|
| 10. |
|
|
| 11. |
- Andréasson, Kristofer, et al.
(författare)
-
Intestinal dysbiosis is common in systemic sclerosis and associated with gastrointestinal and extraintestinal features of disease
- 2016
-
Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 18:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Recent evidence suggests a link between autoimmunity and the intestinal microbial composition in several rheumatic diseases including systemic sclerosis (SSc). The objective of this study was to investigate the prevalence of intestinal dysbiosis in SSc and to characterise patients suffering from this potentially immunomodulatory deviation. Methods: This study consisted of 98 consecutive patients subject to in-hospital care. Stool samples were analysed for intestinal microbiota composition using a validated genome-based microbiota test (GA-map™ Dysbiosis Test, Genetic Analysis, Oslo, Norway). Gut microbiota dysbiosis was found present as per this standardised test. Patients were examined regarding gastrointestinal and extraintestinal manifestations of SSc by clinical, laboratory, and radiological measures including esophageal cineradiography, the Malnutrition Universal Screening Tool (MUST), levels of plasma transthyretin (a marker of malnutrition) and faecal (F-) calprotectin (a marker of intestinal inflammation). Results: A majority (75.5%) of the patients exhibited dysbiosis. Dysbiosis was more severe (rs=0.31, p=0.001) and more common (p=0.013) in patients with esophageal dysmotility. Dysbiosis was also more pronounced in patients with abnormal plasma levels of transthyretin (p=0.045) or micronutrient deficiency (p=0.009). In 19 patients at risk for malnutrition according to the MUST, 18 exhibited dysbiosis. Conversely, of the 24 patients with a negative dysbiosis test, only one was at risk for malnutrition. The mean±SEM levels of F-calprotectin were 112±14 and 45±8μg/g in patients with a positive and negative dysbiosis test, respectively. Dysbiosis was more severe in patients with skin telangiectasias (p=0.020), pitting scars (p=0.023), pulmonary fibrosis (p=0.009), and elevated serum markers of inflammation (p<0.001). However, dysbiosis did not correlate with age, disease duration, disease subtype, or extent of skin fibrosis. Conclusions: In this cross-sectional study, intestinal dysbiosis was common in patients with SSc and was associated with gastrointestinal dysfunction, malnutrition and with some inflammatory, fibrotic and vascular extraintestinal features of SSc. Further studies are needed to elucidate the potential causal relationship of intestinal microbe-host interaction in this autoimmune disease.
|
|
| 12. |
|
|
| 13. |
- Andréasson, Kristofer, et al.
(författare)
-
Limited impact of fibromodulin deficiency on the development of experimental skin fibrosis
- 2016
-
Ingår i: Experimental Dermatology. - : Wiley. - 0906-6705.
-
Tidskriftsartikel (refereegranskat)abstract
- Excessive production of collagen is the hallmark of fatal diseases of fibrosis such as systemic sclerosis. Overexpression of the proteoglycan fibromodulin (FMOD) has been associated with improved wound healing and scarless repair. In this study we have investigated the consequences of FMOD deficiency on the development of experimental skin fibrosis. Using immunohistochemistry, we identified FMOD in both human and murine fibrotic skin. In the bleomycin model of skin fibrosis, FMOD(-/-) mice developed skin fibrosis to a similar degree compared to FMOD(+/+) mice. Analysis of skin ultrastructure using transmission electron microscopy revealed a significant reduction in collagen fibril diameter in FMOD(-/-) but not FMOD(+/+) mice following fibrosis. We conclude that impact of FMOD deficiency on the development of experimental skin fibrosis is limited. This article is protected by copyright. All rights reserved.
|
|
| 14. |
|
|
| 15. |
- Andréasson, Kristofer, et al.
(författare)
-
Mycophenolate mofetil for systemic sclerosis : drug exposure exhibits considerable inter-individual variation-a prospective, observational study
- 2020
-
Ingår i: Arthritis Research & Therapy. - : BMC. - 1478-6362 .- 1478-6354. ; 22
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Mycophenolate mofetil (MMF) is an established therapy for systemic sclerosis (SSc), but its pharmacokinetics in this disease remains unexplored. We have investigated drug exposure in MMF-treated patients with SSc in relation to clinical features of the disease and common concomitant drugs.Methods: This study was predefined to include 35 MMF-treated SSc patients who were using MMF at a fixed dose of 0.5, 1.0 or 1.5g twice daily since at least 3months. The 12-h drug exposure of the active MMF metabolite mycophenolic acid (MPA) was estimated by repeated analysis of plasma MPA over a 6-h period. This 12-h drug exposure was dose normalised to a daily intake of 3g MMF (MPA_AUC(3g)) in order to compare subjects using MMF at different doses. Drug exposure was analysed in reference to the clinical characteristics including body weight, renal function, autoantibodies, intestinal dysbiosis, intestinal inflammation assessed by faecal (F)-calprotectin, intestinal symptoms assessed by the University of California Los Angeles Scleroderma Trial Consortium Gastrointestinal Tract Instrument 2.0 and concomitant drug usage including proton-pump inhibitors (PPI).Results:Thirty-four out of 35 study participants completed the study. The mean daily MMF dose was 2.1g. Drug exposure expressed as MPA_AUC(3g) varied up to 8-fold between patients (median 115, range 27-226mg h/L).MPA_AUC(3g) was inversely related to body weight (r(s)=-0.58, p<0.001) and renal function (r(s)=-0.34, p=0.054). Anti-topoisomerase-1 antibodies and male sex were associated with lower MPA_AUC(3g) (87 vs 123 and 71 vs 141; p=0.008 and p=0.015, respectively). MPA_AUC(3g) was inversely related to the intestinal abundance of lactobacilli and to F-calprotectin (r(s)=-0.54, p=0.004; r(s)=-0.36, p=0.034), but not to gastrointestinal symptoms. MPA_AUC(3g) was inversely related to PPI usage (r(s)=-0.45, p=0.007). We found no association between MPA_AUC(3g) and disease subtype, disease duration or disease activity.Conclusion: MMF-treated SSc patients exhibit considerable inter-individual variation in drug exposure, and lower MPA levels were primarily found in PPI users with poor prognostic factors. Body weight, renal function, sex, serology, gastrointestinal manifestations and/or measuring individual MPA exposure should be considered when using MMF for SSc.
|
|
| 16. |
|
|
| 17. |
- Andréasson, Kristofer, et al.
(författare)
-
Persistent elevation of fibrosis biomarker cartilage oligomeric matrix protein following hepatitis C virus eradication
- 2019
-
Ingår i: World Journal of Hepatology. - : Baishideng Publishing Group Inc.. - 1948-5182. ; 11:3, s. 330-334
-
Tidskriftsartikel (refereegranskat)abstract
- Serum levels of cartilage oligomeric matrix protein (COMP) has been presented as a biomarker of liver fibrosis in several cross-sectional studies. COMP is also an essential mediator in carcinoma development and has also been associated with hepatocellular carcinoma. We present a prospective analysis of this biomarker in 38 patients with chronic hepatitis C who were subject to eradication therapy with direct acting antivirals. We confirm previous studies associating COMP elevation with liver cirrhosis. We also show how viral levels are correlated with COMP at baseline. In our prospective analysis, we report that successful eradication of hepatitis C results in improvement in liver stiffness and laboratory liver function tests at 1 year follow-up. In contrast, median COMP-levels remain unchanged during the study period. We conclude that the biomarker potential of COMP in the prospective evaluation of liver diseases, remains to be elucidated.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Andréasson, Kristofer
(författare)
-
Systemic sclerosis. Novel molecular and epidemiological features of disease.
- 2013
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systemic sclerosis (SSc) is a systemic rheumatic disease with significant mortality and morbidity. Different estimations of disease prevalence and incidence have been presented from various parts of the world. While lung involvement is a common cause of SSc-related death, a majority of SSc patients suffer from symptoms originating in the gastrointestinal (GI) tract. By combining data from a population based register with individual case ascertainment, we investigated the epidemiology of SSc in a defined region in southern Sweden comprising one million adult inhabitants. The investigation was performed by using classification criteria presented in 1980 and in 2013 respectively. SSc prevalence was estimated to 305 per million and the annual incidence 19 per million and year by application of the 2013 classification criteria. We show that the novel criteria identify SSc subjects who were overlooked by the previous criteria. Usage of either criteria set resulted in prevalence estimates that are higher than previous reports from northern Europe, but similar to reports from southern Europe. Cartilage oligomeric matrix protein (COMP) is a promising biomarker of skin fibrosis in SSc. We have investigated the potential for S-COMP to serve as a biomarker for SSc associated lung fibrosis and as a predictor of SSc survival. S-COMP showed only minimal associations with the development or presence of pulmonary fibrosis. SSc patients with pathological S-COMP in early SSc were at an increased risk of death. To further explore the mechanisms behind COMP and fibrosis, we investigated skin fibrosis in mice deficient in COMP. These mice were not resistant to skin fibrosis. GI disease is a common visceral manifestation of SSc. The inflammatory protein complex S100A8/A9, also known as calprotectin, has been associated with several rheumatic diseases. Faecal calprotectin (FC) is a validated biomarker in inflammatory bowel disease. We have explored the biomarker potential of FC in SSc. FC correlated with SSc manifestations in the GI tract. FCs showed little variation upon repeated testing. FC was higher in SSc compared to other rheumatic diseases. The development of inflammation and fibrosis was investigated in reference to S100A8/A9 in an experimental mouse model. S100A8 and S100A9 were found to localise to inflamed and fibrotic skin tissue. Using the same model, we could not identify any significant reduction of inflammation or fibrosis in S100A9 deficient mice. I suggest that FC, a feasible biomarker already available in routine clinical care, could be a valid biomarker of GI disease in SSc. Further studies are warranted to elucidate the mechanisms behind pathological FC testing in SSc.
|
|
| 23. |
- Andréasson, Kristofer, et al.
(författare)
-
Treatment for Rheumatoid Arthritis Associated With Alterations in the Gastrointestinal Microbiota
- 2024
-
Ingår i: ACR Open Rheumatology. - 2578-5745.
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Emerging research suggests that rheumatoid arthritis (RA) is associated with intestinal dysbiosis. This prospective pilot study evaluates changes in intestinal microbial composition in patients with RA initiating treatment with either methotrexate (MTX) or a tumor necrosis factor inhibitor (TNFi). Methods: Consecutive patients, fulfilling the 2010 American College of Rheumatology/EULAR classification criteria for RA, who started treatment with either MTX or TNFi delivered a stool sample upon initiation of immunosuppression and 3 months later. A 16S ribosomal RNA gene-based validated microbiota test (GA-map Dysbiosis Index Score [DIS], Genetic Analysis, Oslo, Norway) was used to evaluate for the presence and degree of dysbiosis. Fecal levels of Prevotella copri (P. copri) were analyzed by custom-made quantitative polymerase chain reaction. Changes in microbial composition were analyzed in relation to changes in disease activity, as measured by the disease activity score based on 28-joint counts, using C-reactive protein. Results: At baseline, dysbiosis was present in 33 of 50 (66%) participants and more common in participants with more than 2 years of disease duration (P = 0.019). At the 3-month follow-up, 27 of 50 (54%) were good treatment responders and the DIS had improved in 14 of 50 (28%). Participants initiating TNFi more often exhibited improvement in the DIS compared with those initiating MTX (P = 0.031). P. copri was identified in 32 of 50 (64%) at baseline. An improvement in disease activity score based on 28-joint counts, using C-reactive protein was associated with a simultaneous decrease in P. copri abundance (rs = 0.30, P = 0.036). Conclusion: This study affirms that dysbiosis is a feature of RA. Although patients were not randomized to MTX or TNFi, the findings suggest that specific therapies may differentially modulate the gastrointestinal microbiota in RA. The association between P. copri and treatment response requires further study.
|
|
| 24. |
- Bartosik, I, et al.
(författare)
-
Vascular events are risk factors for anal incontinence in systemic sclerosis: a study of morphology and functional properties measured by anal endosonography and manometry.
- 2014
-
Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 1502-7732 .- 0300-9742. ; 43:5, s. 391-397
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To study anal sphincter morphology, anal sphincter pressure, and rectoanal inhibitory reflex (RAIR) in patients with systemic sclerosis (SSc) complicated by anal incontinence (AI) and to investigate possible risk factors for AI in SSc. Method: Nineteen SSc patients with severe AI were investigated using anal endosonography, anal manometry, and rectal manovolumetry. To determine risk factors for AI, disease characteristics of SSc patients with AI were compared with those of 95 SSc patients without AI; there were five matched SSc patients without AI for each SSc patient with AI. Results: The mean (SD) internal sphincter thickness was 1.3 (0.46) mm in patients with AI, which was thinner (p < 0.001) than reference data from healthy individuals whose internal sphincter measured 2.2 (0.45) mm, whereas the external sphincter thickness did not differ. The mean (SD) resting pressure in AI patients was lower than the reference data from healthy individuals [60 (22) vs. 94 (29) mmHg, p < 0.002] whereas the squeeze pressure did not differ. Centromeric antibodies and features of vascular disease [i.e. the presence of pulmonary arterial hypertension (PAH), digital ulcers, pitting scars, or the need for iloprost infusions] were associated with AI whereas fibrotic manifestations [i.e. modified Rodnan skin score (mRss), the diffuse cutaneous SSc (dcSSc) subset, or low vital capacity (VC)] were not. Conclusions: SSc patients with AI have a thin internal anal sphincter and a low resting pressure. Risk factors for AI among SSc patients are centromeric antibodies and vascular disease, which supports the hypothesis that gastrointestinal involvement in SSc is in part a vascular manifestation of the disease.
|
|
| 25. |
- Bozovic, Gracijela, et al.
(författare)
-
Exocrine pancreatic function is preserved in systemic sclerosis
- 2019
-
Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 21
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Systemic sclerosis (SSc) has been suggested to cause exocrine pancreatic dysfunction. However, a case-control-based autopsy study failed to associate systemic sclerosis with any pancreatic histopathology. The primary objective of this study was to examine the exocrine pancreatic function in consecutive SSc patients in relation to an age- and sex-matched control group. A secondary objective was to relate exocrine pancreatic function to radiological, laboratory, and clinical SSc characteristics. Methods: One hundred twelve consecutive patients fulfilling the 2013 American Congress of Rheumatology/European League Against Rheumatism criteria for SSc and 52 control subjects were matched for sex and age. Exocrine pancreatic function was assessed by ELISA-based measurement of fecal elastase, and levels <= 200g/g were considered pathological, i.e., representing exocrine pancreatic insufficiency. Patients were characterized regarding SSc manifestations including gastrointestinal and hepatobiliary function, by use of laboratory and clinical examinations. Pancreas parenchyma characteristics were evaluated by high-resolution computer tomography (HRCT). Results: A similar proportion of subjects exhibited pathological levels of fecal elastase among SSc patients (6/112; 5.4%) and control subjects (3/52; 5.8%). Patients with fecal elastase <= 200g/g did not differ from other SSc patients with respect to laboratory and clinical characteristics, including malnutrition. SSc subjects with low levels of fecal elastase displayed significantly lower pancreas attenuation on HRCT examinations compared to the control subjects. Conclusions: In this study encompassing 112 consecutive SSc patients and 52 matched control subjects, we were unable to associate systemic sclerosis with clinically significant exocrine pancreatic dysfunction.
|
|
| 26. |
- Dobrota, Rucsandra, et al.
(författare)
-
Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: a EUSTAR analysis
- 2016
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 75:10, s. 48-1743
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Improvement of skin fibrosis is part of the natural course of diffuse cutaneous systemic sclerosis (dcSSc). Recognising those patients most likely to improve could help tailoring clinical management and cohort enrichment for clinical trials. In this study, we aimed to identify predictors for improvement of skin fibrosis in patients with dcSSc.METHODS: We performed a longitudinal analysis of the European Scleroderma Trials And Research (EUSTAR) registry including patients with dcSSc, fulfilling American College of Rheumatology criteria, baseline modified Rodnan skin score (mRSS) ≥7 and follow-up mRSS at 12±2 months. The primary outcome was skin improvement (decrease in mRSS of >5 points and ≥25%) at 1 year follow-up. A respective increase in mRSS was considered progression. Candidate predictors for skin improvement were selected by expert opinion and logistic regression with bootstrap validation was applied.RESULTS: From the 919 patients included, 218 (24%) improved and 95 (10%) progressed. Eleven candidate predictors for skin improvement were analysed. The final model identified high baseline mRSS and absence of tendon friction rubs as independent predictors of skin improvement. The baseline mRSS was the strongest predictor of skin improvement, independent of disease duration. An upper threshold between 18 and 25 performed best in enriching for progressors over regressors.CONCLUSIONS: Patients with advanced skin fibrosis at baseline and absence of tendon friction rubs are more likely to regress in the next year than patients with milder skin fibrosis. These evidence-based data can be implemented in clinical trial design to minimise the inclusion of patients who would regress under standard of care.
|
|
| 27. |
- Grankvist, Anna, et al.
(författare)
-
Multi-locus sequence analysis (MLSA) of clinical "CandidatusNeoehrlichia mikurensis" strains from Europe.
- 2015
-
Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 53:10, s. 3126-3132
-
Tidskriftsartikel (refereegranskat)abstract
- CandidatusNeoehrlichia mikurensis is the tick-borne agent of neoehrlichiosis, an infectious disease that primarily affects immunocompromised patients. So far, the genetic variability of Neoehrlichia has been studied only by comparing 16S rRNA gene and groEL operon sequences. We describe the development and use of a multi-locus sequence analysis (MLSA) protocol to characterize the genetic diversity of clinicalNeoehrlichiastrains in Europe and their relatedness to other species within the Anaplasmataceae family.Six genes were selected:ftsZ, clpB, gatB,lipA,groEL and 16SrRNA. Each MLSA locus was amplified by real-time PCR, and the PCR-products sequenced. Phylogenetic trees of MLSA locus relatedness were constructed from aligned sequences. Blood samples from 12 patients with confirmed Neoehrlichia infection from Sweden (n = 9), the Czech Republic (n = 2) and Germany (n = 1) were analyzed with the MLSA protocol.Threeof the Swedish strains exhibited identical lipA sequences, while the lipA sequences of the strains from the other nine patients were identical to each other.One of the Czech strains had one differing nucleotide in the clpB sequence from the sequences of the other 11 strains. All 12 strains had identical sequences for the genes 16SrRNA,ftsZ, gatB, and groEL.According to the MLSA, Neoehrlichia is most closely related to E. ruminantium, less so to A. phagocytophilum and least to Wolbachiaendosymbiont, among the Anaplasmataceae.To conclude, three sequence types of infectious Neoehrlichia wereidentified: one in the west of Sweden, one in the Czech Republic, and one spread throughout Europe.
|
|
| 28. |
- Hamberg, Viggo, et al.
(författare)
-
Anti-Ro52 positivity is associated with progressive interstitial lung disease in systemic sclerosis-an exploratory study
- 2023
-
Ingår i: Arthritis Research & Therapy. - : BioMed Central (BMC). - 1478-6362 .- 1478-6354. ; 25, s. 1-13
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Interstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc). Prognostic biomarkers are needed to identify SSc-ILD patients at risk for progressive pulmonary fibrosis. This study investigates autoantibodies measured in bronchoalveolar lavage (BAL) fluid and in serum in reference to the clinical disease course of SSc-ILD.Methods: Fifteen patients with new onset SSc-ILD underwent bronchoscopy. Autoantibody levels were analyzed using addressable laser bead immunoassay from BAL fluid and the serum. In a separate longitudinal cohort of 43 patients with early SSc-ILD, autoantibodies in serum were measured at baseline and pulmonary function tests were performed at least 2 times over the course of at least 2 or more years. Linear mixed effect models were created to investigate the relationship between specific autoantibodies and progression of SSc-ILD. Finally, lung tissue from healthy controls and from subjects with SSc was analyzed for the presence of the Ro52 antigen using immunohistochemistry.Results: Among SSc-ILD patients who were positive for anti-Ro52 (N = 5), 3 (60%) had enrichment of anti-Ro52 in BAL fluid at a ratio exceeding 50x. In the longitudinal cohort, 10/43 patients (23%) were anti-Ro52 positive and 16/43 (37%) were anti-scl-70 positive. Presence of anti-Scl-70 was associated with a lower vital capacity (VC) at baseline (-12.6% predicted VC [%pVC]; 95%CI: -25.0, -0.29; p = 0.045), but was not significantly associated with loss of lung function over time (-1.07%pVC/year; 95%CI: -2.86, 0.71; p = 0.230). The presence of anti-Ro52 was significantly associated with the loss of lung function over time (-2.41%pVC/year; 95% CI: -4.28, -0.54; p = 0.013). Rate of loss of lung function increased linearly with increasing anti-Ro52 antibody levels (-0.03%pVC per arbitrary units/mL and year; 95%CI: -0.05, -0.02; p < 0.001). Immunohistochemical staining localized the Ro52 antigen to alveolar M2 macrophages in peripheral lung tissue both in subjects with and without SSc.Conclusions: This study suggests that antibodies targeting Ro52 are enriched in the lungs of patients with new-onset SSc-ILD, linking Ro52 autoimmunity to the pulmonary pathology of SSc. Clinical and immunohistochemical data corroborates these findings and suggest that anti-Ro52 may serve as a potential biomarker of progressive SSc-ILD.
|
|
| 29. |
- Hamberg, Viggo, et al.
(författare)
-
Elevated fecal levels of the inflammatory biomarker calprotectin in early systemic sclerosis
- 2023
-
Ingår i: Rheumatology International. - : Springer Science and Business Media LLC. - 0172-8172 .- 1437-160X. ; 43:5, s. 961-967
-
Tidskriftsartikel (refereegranskat)abstract
- Knowledge on gastrointestinal manifestations in early systemic sclerosis (SSc) is limited. We have investigated gastrointestinal inflammation in SSc at the time of diagnosis using the inflammatory biomarker Fecal calprotectin (F-cal). Consecutive patients with suspected SSc were characterized in relation to the 2013 classification criteria for SSc and classified as SSc or SSc-like disease. F-cal levels were measured with a polyclonal ELISA (Calpro A/S, Lysaker, Norway) and levels above 50 µg/g were considered elevated. F-cal levels were compared to those of control subjects without rheumatic disease. Of 137 patients with suspected SSc, 92 were classified as SSc and 45 as SSc-like disease. Median (interquartile range) disease duration among the SSc participants was 2.5 (1.2, 4.6) years. A substantial proportion of participants classified as SSc (35/92, 38%) and SSc-like disease (14/45, 31%) exhibited elevated F-cal compared to the control group (3/41, 7.3%; p < 0.001 and p = 0.007, respectively). Elevated F-cal was associated with proton pump inhibitor usage (OR 7.14; 95% CI 2.56–29.93; p < 0.001). We conclude that elevated F-cal is present in a subgroup of patients with SSc at the time of diagnosis, suggesting that that GI inflammation may be present in this patient group early in the disease course. F-cal did not exhibit potential to differentiate SSc from SSc-like disease.
|
|
| 30. |
- Hesselstrand, Roger, et al.
(författare)
-
Biomarkers from bronchoalveolar lavage fluid in systemic sclerosis patients with interstitial lung disease relate to severity of lung fibrosis.
- 2013
-
Ingår i: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 107:7, s. 1079-1086
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Decision on treatment of systemic sclerosis (SSc) related interstitial lung disease (ILD) largely relies on the findings on high resolution computed tomography (HRCT) and there is a need for improvement in assessment of the fibrotic activity. The objectives of this study were to study biomarkers in bronchoalveolar lavage fluid (BALF) from SSc patients with ILD and to relate the findings to the severity and activity of lung fibrosis. METHODS: Fifteen patients with early SSc and 12 healthy controls were subjected to BAL. Cell counts and analyses of CXCL5, CXCL8 and S100A8/A9 were performed in BALF and serum. COMP and KL-6 were measured in serum. HRCT of lungs was quantified for ground glass opacities (GGO), reticulation and traction bronchiectases. RESULTS: BALF concentrations of CXCL8 (p < 0.001), CXCL5 (p = 0.002) and S100A8/A9 (p = 0.016) were higher in patients than controls. Serum KL-6 (p < 0.001) was increased in SSc patients and correlated with BALF concentration of eosinophils (rS = 0.57, p = 0.027). Patients with more widespread GGO on HRCT were characterised in BALF by a higher eosinophil count (p = 0.002) and in serum by higher KL-6 (p = 0.008). Patients with more fibrosis were characterised in BALF by higher eosinophil count (p = 0.014), higher CXCL8 (p = 0.005) and S100A8A/A9 (p = 0.014) concentration and in serum by a higher serum COMP (p = 0.023). CONCLUSIONS: In SSc related ILD, biomarkers from BALF and serum correlate to findings on HRCT suggesting usefulness as markers of presence and extent of lung fibrosis.
|
|
| 31. |
- Hesselstrand, Roger, et al.
(författare)
-
High frequency ultrasound of skin involvement in systemic sclerosis - a follow-up study.
- 2015
-
Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- High-frequency ultrasound offers a potential for objective and quantitative assessment of skin thickness and skin echogenicity in systemic sclerosis (SSc). Few studies have however assessed the longitudinal changes of skin involvement using ultrasound. The aim of the study was to investigate changes in skin thickness in early SSc using high frequency ultrasound during one year of follow-up in comparison to other measurements of skin fibrosis.
|
|
| 32. |
- Hesselstrand, Roger, et al.
(författare)
-
Increased serum COMP predicts mortality in SSc: results from a longitudinal study of interstitial lung disease.
- 2012
-
Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 51:5, s. 915-920
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives. COMP is a regulator of assembly and maintenance of the fibrillar collagen I and II networks. Serum COMP reflects skin fibrosis in SSc. The purpose of this study was to examine whether serum COMP reflects fibrotic lung involvement in SSc patients and to study if serum COMP predicts mortality.Methods. Three overlapping cohorts of 244 SSc patients were studied. Two hundred and eighteen patients were included to study survival, 80 patients to study longitudinal changes of pulmonary function tests and 64 to study pulmonary involvement assessed by high-resolution CT (HRCT). Serum COMP was measured by ELISA. Skin involvement was assessed with the modified Rodnan skin score (mRSS). Data about survival were obtained from the central population registry.Results. Serum COMP measured within 5 years after the first non-Raynaud's manifestation was a predictor of death, and crude mortality increased by 6% for each COMP unit elevation. Serum COMP levels >15 U/l were associated with a 3.13-fold (95% CI 1.73, 5.64; P < 0.001) increased risk of death. During the first year of follow-up serum COMP and vital capacity (VC) changed inversely (r(s) = -0.32; P = 0.005), but there were no correlations between baseline serum COMP and concurrent findings by spirometry or HRCT.Conclusion. Serum COMP early in disease is a predictor of mortality in SSc patients. Serum COMP changes in parallel with lung fibrosis as measured by VC, but the release from fibrotic skin possibly obscures the influx from the lungs and therefore serum COMP seems to have little utility as a marker of lung fibrosis.
|
|
| 33. |
- Lepri, Gemma, et al.
(författare)
-
Systemic sclerosis and primary biliary cholangitis : Longitudinal data to determine the outcomes
- 2023
-
Ingår i: Journal of Scleroderma and Related Disorders. - 2397-1983. ; 8:3, s. 210-220
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies described the cross-sectional characteristics of systemic sclerosis patients and coexisting primary biliary cholangitis, but longitudinal prognostic data are lacking. Aims: To describe the systemic sclerosis–primary biliary cholangitis phenotype, including baseline characteristics and outcomes. Methods: We performed a multicentre the European Scleroderma Trials and Research Group study of systemic sclerosis patients with primary biliary cholangitis or with primary biliary cholangitis–specific antibodies, matched with systemic sclerosis controls free from hepatobiliary involvement matched for disease duration and cutaneous subset. Data were recorded at baseline and at the last available visit. Results: A total of 261 patients were enrolled (115 primary biliary cholangitis–systemic sclerosis, 161 systemic sclerosis). At baseline, systemic sclerosis–primary biliary cholangitis patients had a higher prevalence of anti-centromere antibodies (p = 0.0023) and a lower prevalence of complete absence of digital ulcers. The milder vascular involvement was confirmed at follow-up when crucial differences emerged in the percentage of patients experiencing digital ulcers; a significantly higher number of patients who never experienced digital ulcers were observed among primary biliary cholangitis–systemic sclerosis patients (p = 0.0015). Moreover, a greater incidence of pulmonary arterial hypertension (p < 0.001) and of conduction blocks (p = 0.0256) was observed in systemic sclerosis patients without primary biliary cholangitis. Patients with primary biliary cholangitis had higher levels of liver enzymes at baseline than systemic sclerosis patients; a significant decrease in liver enzymes was observed at follow-up. Out of 18 patients with cholangitis, one received a liver transplant at follow-up. Conclusion: Our data show that systemic sclerosis–primary biliary cholangitis exhibit a mild systemic sclerosis and primary biliary cholangitis phenotype with outcomes being in general favourable.
|
|
| 34. |
- Mandl, Thomas, et al.
(författare)
-
Severe intestinal dysbiosis is prevalent in primary Sjögren's syndrome and is associated with systemic disease activity.
- 2017
-
Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Altered microbial composition of the intestine, commonly referred to as dysbiosis, has been associated with several autoimmune diseases including primary Sjögren’s syndrome (pSS). The aims of the current study were to study the intestinal microbial balance in pSS and to identify clinical features associated with dysbiosis.
|
|
| 35. |
- Nguyen, Audrey D., et al.
(författare)
-
Gastrointestinal tract involvement in systemic sclerosis : The roles of diet and the microbiome
- 2023
-
Ingår i: Seminars in Arthritis and Rheumatism. - : Elsevier BV. - 0049-0172. ; 60
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Alterations in gastrointestinal (GI) microbial composition have been reported in patients with systemic sclerosis (SSc). However, it is unclear to what degree these alterations and/or dietary changes contribute to the SSc-GI phenotype. Objectives: Our study aimed to 1) evaluate the relationship between GI microbial composition and SSc-GI symptoms, and 2) compare GI symptoms and GI microbial composition between SSc patients adhering to a low versus non-low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet. Methods: Adult SSc patients were consecutively recruited to provide stool specimens for bacterial 16S rRNA gene sequencing. Patients completed the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (GIT 2.0) and the Diet History Questionnaire (DHQ) II and were classified as adhering to a low or non-low FODMAP diet. GI microbial differences were assessed using three metrics of alpha diversity (species richness, evenness, and phylogenetic diversity), as well as beta diversity (overall microbial composition). Differential abundance analysis was performed to identify specific genera associated with SSc-GI phenotype and low versus non-low FODMAP diet. Results: Of the 66 total SSc patients included, the majority were women (n = 56) with a mean disease duration of 9.6 years. Thirty-five participants completed the DHQ II. Increased severity of GI symptoms (total GIT 2.0 score) was associated with decreased species diversity and differences in GI microbial composition. Specifically, pathobiont genera (e.g., Klebsiella and Enterococcus) were significantly more abundant in patients with increased GI symptom severity. When comparing low (N = 19) versus non-low (N = 16) FODMAP groups, there were no significant differences in GI symptom severity or in alpha and beta diversity. Compared with the low FODMAP group, the non-low FODMAP group had greater abundance of the pathobiont Enterococcus. Conclusion: SSc patients reporting more severe GI symptoms exhibited GI microbial dysbiosis characterized by less species diversity and alterations in microbial composition. A low FODMAP diet was not associated with significant alterations in GI microbial composition or reduced SSc-GI symptoms; however, randomized controlled trials are needed to evaluate the impact of specific diets on GI symptoms in SSc.
|
|
| 36. |
- Nielsen, Christel, et al.
(författare)
-
Cohort profile : The Swedish Tattoo and Body Modifications Cohort (TABOO)
- 2023
-
Ingår i: BMJ Open. - 2044-6055. ; 13:5
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The Swedish Tattoo and Body Modifications Cohort (TABOO) cohort was established to provide an infrastructure for epidemiological studies researching the role of tattoos and other body modifications as risk factors for adverse health outcomes. It is the first population-based cohort with detailed exposure assessment of decorative, cosmetic, and medical tattoos, piercing, scarification, henna tattoos, cosmetic laser treatments, hair dyeing, and sun habits. The level of detail in the exposure assessment of tattoos allows for investigation of crude dose-response relationships.PARTICIPANTS: The TABOO cohort includes 13 049 individuals that participated in a questionnaire survey conducted in 2021 (response rate 49%). Outcome data are retrieved from the National Patient Register, the National Prescribed Drug Register and the National Cause of Death Register. Participation in the registers is regulated by Swedish law, which eliminates the risk of loss to follow-up and associated selection bias.FINDINGS TO DATE: The tattoo prevalence in TABOO is 21%. The cohort is currently used to clarify the incidence of acute and long-lasting health complaints after tattooing based on self-reported data. Using register-based outcome data, we are investigating the role of tattoos as a risk factor for immune-mediated disease, including hypersensitisation, foreign body reactions and autoimmune conditions.FUTURE PLANS: The register linkage will be renewed every third year to update the outcome data, and we have ethical approval to reapproach the responders with additional questionnaires.
|
|
| 37. |
- Olofsson, Tor, et al.
(författare)
-
Elevated faecal calprotectin is linked to worse disease status in axial spondyloarthritis : Results from the SPARTAKUS cohort
- 2019
-
Ingår i: Rheumatology (United Kingdom). - : Oxford University Press (OUP). - 1462-0324 .- 1462-0332. ; 58:7, s. 1176-1187
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives. To examine faecal calprotectin (F-calprotectin) levels and presence of anti-Saccharomyces cerevisiae antibodies (ASCA) and their associations with disease subtype and current status in axial SpA (axSpA). Methods. F-calprotectin and ASCA in serum were compared between consecutive patients with a clinical axSpA diagnosis, classified as non-radiographic axSpA (nr-axSpA; n = 40) or AS (n = 90), and with healthy controls (n = 35). Furthermore, standard axSpA outcome measures were compared between axSpA patients (nr-axSpA and AS combined) with elevated vs normal F-calprotectin, ASCA IgA and IgG, respectively. Results. Elevated F-calprotectin (≥50 mg/kg) was observed in 27% of nr-axSpA patients, 38% of AS patients and 6% of controls. F-calprotectin was significantly higher in AS vs nr-axSpA [AS: geometric mean 41 (95% CI 32, 54) mg/kg; nr-axSpA: 24 (95% CI 16, 38) mg/kg; P = 0.037], and in each axSpA subtype vs controls. Overall, worse disease activity and physical function scores were observed among axSpA patients with elevated vs normal F-calprotectin levels, with significant differences regarding patient's visual analogue scale for global health, ASDAS using CRP, and BASFI (adjusted for age, sex, NSAID use, anti-rheumatic treatments, and CRP). ASCA titres and seropositivity (≥10 U/ml) were similar in nr-axSpA (IgA/IgG-seropositivity: 8%/26%) and AS (7%/28%), and clinical outcome measures did not differ between patients with elevated vs normal ASCA IgA or IgG, respectively. Compared with controls (IgA/IgG-seropositivity: 0%/17%), ASCA IgA was significantly higher in both axSpA subtypes, and IgG was significantly higher in the AS group. Conclusion. In patients with axSpA, gut inflammation measured by elevated F-calprotectin is associated with worse disease activity and physical function, and may be a marker of more severe disease.
|
|
| 38. |
- Rydell-Törmänen, Kristina, et al.
(författare)
-
Absence of fibromodulin affects matrix composition, collagen deposition and cell turnover in healthy and fibrotic lung parenchyma.
- 2014
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- The ECM exerts great effects on cells, and changed composition may therefore have profound impact. Small leucine-rich proteoglycans, e.g. fibromodulin, are essential in collagen assembly. Our aim was to investigate the role of fibromodulin in healthy and fibrotic lung parenchyma, theorizing that fibromodulin-deficient animals would be protected against fibrosis. Repeated subcutaneous bleomycin-injections were given to wild type and fibromodulin-deficient mice, inducing pulmonary fibrosis. Development of fibrosis, ECM composition, cell turnover and inflammatory responses were investigated. Fibromodulin-deficient animals were not protected from fibrosis, but the composition of the matrix was affected, with decreased Collagen I in fibromodulin-deficient animals, both in controls (0.07 ± 0.04% vs. 0.18 ± 0.07% tissue area) and after bleomycin (0.37 ± 0.16% vs. 0.61 ± 0.21% tissue area). Biglycan was increased in fibromodulin-deficient animals, whereas decorin was decreased. Furthermore, bleomycin increased cell turnover in wild type, but only proliferation in fibromodulin-deficient animals, resulting in hyperplasia. In addition, the bleomycin-induced immune response was affected in fibromodulin-deficient animals. We thus conclude that fibromodulin has a profound effect on ECM, both in healthy and fibrotic lung parenchyma, and may be providing a permissive microenvironment affecting cell turnover. Furthermore, this study highlights the need to acknowledge specific ECM components, when assessing tissue properties and ultimately cell behaviour.
|
|
| 39. |
- Rydell-Törmänen, Kristina, et al.
(författare)
-
Extracellular matrix alterations and acute inflammation; developing in parallel during early induction of pulmonary fibrosis.
- 2012
-
Ingår i: Laboratory Investigation. - : Elsevier BV. - 1530-0307 .- 0023-6837. ; 92:6, s. 917-925
-
Tidskriftsartikel (refereegranskat)abstract
- Pulmonary fibrosis is a hallmark of several systemic diseases such as systemic sclerosis. Initiation and early development is not well characterized, as initiation usually is unnoticed in patients, yet fibrosis has been considered a late event, occurring after an inflammatory phase. By utilizing an animal model, the starting point can be defined and the initiation process and early development thoroughly investigated. To investigate these processes from a systemic perspective, we choose a systemic administration route, instead of the more commonly used local administration. The aim of this work was to study the initiation of pulmonary fibrosis in an animal model and to investigate early alterations in connective tissue, cell turnover and acute immune response in lung parenchyma. Animals were injected subcutaneously with bleomycin, three times a week (w) for 1-4w (controls received saline). Total collagen was histologically assessed by Picro Sirius Red and Masson's Trichrome, collagen production by antibodies directed against N-terminal of procollagens I and III, proliferation by labeling with proliferating cell nuclear antigen, apoptosis by TUNEL and innate immunity by detecting neutrophils and macrophages. Total collagen was significantly increased at 1, 2 and 4w compared with controls. Procollagen I, was increased at 1w and remained increased, whereas procollagen III-staining was increased at 2w, compared with controls. Myofibroblasts were increased at all times as were proliferation, whereas apoptosis was increased from 2w. Neutrophils peaked at 1w (2779±820 cells/mm(2)) and gradually decreased, whereas macrophages peaked at 2w (135±29 cells/mm(2)). Subcutaneously administered bleomycin induces rapid alterations in connective tissue and cell turnover, suggesting a plasticity of the connective tissue. A transient neutrophilia is detected and increased number of macrophages likely represents a clearance process of said neutrophils. The study suggests fibrosis initiation and acute inflammation to occur in parallel in this model.Laboratory Investigation advance online publication, 2 April 2012; doi:10.1038/labinvest.2012.57.
|
|
| 40. |
- Sagard, Jonas, et al.
(författare)
-
Gut dysbiosis associated with worse disease activity and physical function in axial spondyloarthritis
- 2022
-
Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6354 .- 1478-6362. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Based on clinical and genetic associations, axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) are suspected to have a linked pathogenesis. Gut dysbiosis, intrinsic to IBD, has also been observed in axSpA. It is, however, not established to what degree gut dysbiosis is associated with axSpA disease severity. The objective of this study was to compare gut dysbiosis frequency between controls, non-radiographic axial spondyloarthritis (nr-axSpA), and ankylosing spondylitis (AS) patients and investigate whether gut dysbiosis is cross-sectionally associated with axSpA disease activity, physical function, mobility, or pain. Methods Gut dysbiosis was assessed by 16SrRNA analysis of feces from 44/88 nr-axSpA/AS patients (ASAS/mNY criteria) without inflammatory bowel disease (IBD) and 46 controls without IBD or rheumatic disease. The GA-map (TM) Dysbiosis Test was used, grading gut microbiota aberrations on a 1-5 scale, where >= 3 denotes dysbiosis. Proportions with dysbiosis were compared between the groups. Furthermore, standard axSpA measures of disease activity, function, mobility, and pain were compared between patients (nr-axSpA and AS combined) with and without dysbiosis, univariately, and adjusted for relevant confounders (ANCOVA). Results Gut dysbiosis was more frequent in AS than controls (36% versus 17%, p=0.023), while nr-axSpA (25% dysbiosis) did not differ significantly from either AS or controls. Univariately, most axSpA measures were significantly worse in patients with dysbiosis versus those without: ASDAS-CRP between-group difference 0.6 (95% CI 0.2-0.9); BASDAI 1.6 (0.8-2.4); evaluator's global disease activity assessment (Likert scale 0-4) 0.3 (0.1-0.5), BASFI 1.5 (0.6-2.4), and VAS pain (cm) 1.3 (0.4-2.2). Differences remained significant after adjustment for demographics, lifestyle factors, treatments, gut inflammation (fecal calprotectin >= 50 mg/kg), and gut symptoms, except for VAS pain. BASMI and CRP were not associated with dysbiosis. Conclusion Gut dysbiosis, more frequent in AS patients than controls, is associated with worse axSpA disease activity and physical function, seemingly irrespective of both gut inflammation and treatments. This provides further evidence for an important link between disturbances in gastrointestinal homeostasis and axSpA.
|
|
| 41. |
- Volkmann, Elizabeth R., et al.
(författare)
-
Systemic sclerosis
- 2023
-
Ingår i: The Lancet. - 0140-6736. ; 401:10373, s. 304-318
-
Forskningsöversikt (refereegranskat)abstract
- Systemic sclerosis, also known as scleroderma, is a rare and complex autoimmune connective-tissue disease. Once considered an untreatable and unpredictable condition, research advancements have improved our understanding of its disease pathogenesis and clinical phenotypes and expanded our treatment armamentarium. Early and accurate diagnosis is essential, while ongoing efforts to risk stratify patients have a central role in predicting both organ involvement and disease progression. A holistic approach is required when choosing the optimal therapeutic strategy, balancing the side-effect profile with efficacy and tailoring the treatment according to the goals of care of the patient. This Seminar reviews the multiple clinical dimensions of systemic sclerosis, beginning at a precursor very early stage of disease, with a focus on timely early detection of organ involvement. This Seminar also summarises management considerations according to the pathological hallmarks of systemic sclerosis (eg, inflammation, fibrosis, and vasculopathy) and highlights unmet needs and opportunities for future research and discovery.
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- Wildt, Marie, et al.
(författare)
-
Treatment with mycophenolate mofetil is associated with improved nailfold vasculature in systemic sclerosis
-
Ingår i: Rheumatology (Oxford, England). - 1462-0332.
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the evolution of nailfold capillary density in patients with systemic sclerosis (SSc) in relation to immunosupressive treatment and autoantibodies.METHODS: Prospective study cohort. Consecutive newly diagnosed SSc patients were included into this study who, in a retrospective review, had at least 2 nailfold capillary microscopy (NCM) measurements performed during the first 48 months of follow-up. Capillary density per 3 mm was measured with widefield NCM. Improvement of capillary density per finger and mean capillary density were analysed. Longitudinal measurements of mean capillary density were analysed by generalized estimating equation (GEE).RESULTS: Eighty patients (68 women, 12 men) met the inclusion criteria. The median follow-up time was 27 months. Twenty-eight patients had an improved capillary density in per finger analysis. Mycophenolate mofetil (MMF) was associated with less numbers of fingers that had worsened in capillary density. Anti-topoisomerase antibodies were associated with low mean capillary density. Anti-RNA polymerase III antibodies were associated with improvement and anti-centromere antibodies with worsening of capillary density in per finger analysis. MMF treatment was associated with less steep capillary density decline in a moderated GEE model including presence of anti-topoisomerase antibodies and the interaction of MMF with follow-up time.CONCLUSION: Nailfold capillary density improved over time in a substantial proportion of SSc patients. MMF treatment had a positive impact on the evolution of capillary density in these patients. SSc autoantibody phenotype may affect the capillary density development. The data support previous hypotheses that early immunosuppression may favourably affect vascular regeneration in SSc.
|
|
