| 1. |
- Eriksson, Per, 1958-, et al.
(författare)
-
Relationship between serum levels of IL-18 and IgG1 in patients with primary Sjögren's syndrome, rheumatoid arthritis and healthy controls
- 2004
-
Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 137:3, s. 617-620
-
Tidskriftsartikel (refereegranskat)abstract
- Primary Sjögren's syndrome (SS) is characterized by inflammation in salivary and lachrymal glands, with a local predominance of Th1-like cytokines, as well as the pleiotropic cytokine interleukin (IL) 18. High serum levels of polyclonal IgG are common, with a subclass imbalance in which IgG1 is increased and IgG2 is normal or low. IL-18 is also of pathogenetic importance in rheumatoid arthritis. In the present study we looked for any relationship between serum IL-18 as well as transforming growth factor (TGF) β1 versus IgA, IgM, and IgG subclass levels in SS (n = 16), rheumatoid arthritis (RA) (n = 15), and healthy controls (n = 15). SS was defined by the revised American-European classification criteria. IL-18 and TGF-β1 were analyzed with enzyme immunoassays (EIA), and IgG1, IgG2 and IgG3 by single radial immunodiffusion. In the composite group of RA, SS and normal controls, IgG1 and IL-18 were related (R = 0.52, P = 0.0005). No relation was found neither between IL-18 versus IgG2, IgG3 or IgA, nor between serum TGF-β1 versus any of the immunoglobulins. Since serum levels of IL-18 are related to serum IgG1, IL-18 may be of importance for IgG1 switch and/or release.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Nilsson, Bengt-Olof, 1954-, et al.
(författare)
-
Antinuclear antibodies in the oldest-old women and men
- 2006
-
Ingår i: Journal of Autoimmun. - : Elsevier. ; 27:4, s. 281-288
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare the prevalence of antinuclear antibodies (ANA) in very old individuals (>/=86years of age) with healthy younger (18-68years) blood donors (n=200) regarding gender, health status, ratio of circulating CD4/CD8 cells and cytomegalovirus (CMV) serology. Frozen plasma was used for ANA detection in two study groups, i.e. 'OCTO' (97 persons aged 86-92years, 65% women) and 'NONA' (136 persons aged 86-95years, 70% women). OCTO participants were recruited on the basis that they were healthy or moderately healthy according to a selection protocol. No exclusion criteria regarding health status were applied in the NONA sample. The prevalence of ANA was significantly higher in the oldest-old samples compared to blood donors. There was no association between health status and the presence of ANA in the oldest-old. The difference across age was most pro-nounced in men, with low levels at younger age, whereas the prevalence among the oldest-old men reached similar levels as in women. There were no associations between the presence of ANA and CD4/CD8 ratio or with CMV status in the oldest-old. Our findings confirm an in-creased prevalence of ANA in the oldest-old, and emphasize the importance of taking gender and age into consideration when evaluating ANA.
|
|
| 5. |
- Reckner Olsson, Åsa, 1965-, et al.
(författare)
-
Allergic manifestations in patients with rheumatoid arthritis
- 2003
-
Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 111:10, s. 940-944
-
Tidskriftsartikel (refereegranskat)abstract
- A functional dichotomy between Th1- and Th2-type immune responses has been suggested. This study was performed to investigate whether rheumatoid arthritis (RA), a disease with indications of Th1-deviated immune activation, is inversly related to atopic conditions which are Th2-mediated. Two hundred and sixty-three adult cases of RA, fulfilling the American Rheumatism Association (ARA) 1987 Revised Classification Criteria for RA, were identified in 1995 and compared with 541 randomly selected population referents. The presence of atopic manifestations was established through a postal questionnaire and by demonstrating circulating IgE antibodies to common allergens. RA was inversely associated with certain manifestations of rhinitis, which were regarded as the most reliable indicators of atopic disease in the present study. However, no negative association was seen between RA and asthma and eczema, respectively. The main results give some support for an inverse relationship between RA and rhinitis. The prevalence of circulating IgE antibodies was however similar in cases and controls, suggesting that the T-cell commitment mainly occurs in the affected organs.
|
|
| 6. |
- Wirestam, Lina, 1986-, et al.
(författare)
-
Osteopontin and disease activity in patients with recent-onset systemic Lupus Erythematosus : Results from the SLICC Inception Cohort
- 2019
-
Ingår i: Journal of Rheumatology. - : The Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 46:5, s. 492-500
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes. Methods. We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively. Results. Compared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01). Conclusion. The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.
|
|
| 7. |
- Carlsson, Alexandra Dimitrijevic, et al.
(författare)
-
Orofacial pain in juvenile idiopathic arthritis is associated with stress as well as psychosocial and functional limitations
- 2019
-
Ingår i: Pediatric Rheumatology. - : BioMed Central (BMC). - 1546-0096. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background The aim of this study was to investigate relations between psychosocial factors, signs and symptoms of orofacial pain and jaw dysfunction in patients with juvenile idiopathic arthritis (JIA). Methods Forty-five patients with JIA (median age 12 years) and 16 healthy matched controls (median age 13 years) were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The subjects answered the DC/TMD questionnaires regarding psychosocial factors (pain intensity, pain-related disability, depression, stress, catastrophizing, pain locations and jaw function). Results JIA patients with orofacial pain had higher degree of stress, depression, catastrophizing and jaw dysfunction compared to subjects without. In turn, these factors were associated with orofacial pain intensity. Also, patients with orofacial pain had higher systemic inflammatory activity. Conclusions Orofacial pain in patients with JIA is associated with stress, psychological distress, jaw dysfunction and loss of daily living activities. Pain intensity seems to be the major pain aspect related to these factors. In addition, systemic inflammatory activity appears to be an important factor contributing to orofacial pain in JIA.
|
|
| 8. |
- Dahle, Charlotte, 1956-, et al.
(författare)
-
Methods of choice for diagnostic antinuclear antibody (ANA) screening : Benefit of adding antigen-specific assays to immunofluorescence microscopy
- 2004
-
Ingår i: Journal of Autoimmunity. - : Elsevier BV. - 0896-8411 .- 1095-9157. ; 22:3, s. 241-248
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives. To evaluate and compare the performances of three enzyme-immunoassays (EIAs) and a double radial immunodiffusion (DRID) test in addition to immunofluorescence (IF) microscopy for routine laboratory screening of patient sera sent for antinuclear antibody (ANA) analysis. Methods. 3079 consecutive patient sera sent for routine testing of ANA were analysed by IF microscopy on HEp-2 cells (IF-ANA), three different ANA-EIAs, and a DRID test for antibodies against extractable nuclear antigens. The IF-ANA and DRID tests were regarded as reference methods. Results. By IF-ANA and/or DRID, 375 sera (12%) turned out ANA-positive. A further 171 sera (6%) were positive by EIA, but could not be confirmed either by IF microscopy or DRID. 32 of the 375 ANA-positive (9%) sera were negative by IF microscopy, but had precipitating antibodies against Ro/SS-A (52 and/or 60 kD). Conclusions. Different assays for ANA analysis give overlapping results to a certain extent, but are by no means interchangeable. Thus, different ANA tests reflect different aspects of these autoantibodies. The diagnostic utility of ANA testing still mainly refers to IF-microscopy and precipitin tests. IF-ANA should not be abandoned as the golden standard in clinical routine, until diagnostic and classification criteria for systemic lupus erythematosus and other systemic inflammatory autoimmune diseases have been revised. However, in addition we strongly advocate that a specific test for anti-Ro/SS-A antibodies is always included.
|
|
| 9. |
- Frodlund, Martina, 1978-
(författare)
-
Antinuclear and antiphospholipid antibodies versus disease manifestations and clinical outcomes in systemic lupus erythematosus
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systemic lupus erythematosus (SLE) has an exceptionally heterogeneous clinical spectrum, ranging from mild disease limited to skin and joints to severe manifestations with renal disorder, central nervous system disease, severe cytopenias and thromboembolic events. Important clinical challenges include the prediction of disease flares and the identification of individuals that are likely to evolve severe disease with accrual of organ damage and worse prognosis. Autoantibodies, i.e. antinuclear antibodies (ANA) and antiphospholipid antibodies (aPL), and interferon alpha (IFN-α) that contribute to formation of immune complexes with nuclear antigens, are hallmarks considered to drive the disease in a vicious circle of antigen exposure, autoantibody production, inflammation and organ damage. There are few good biomarkers to predict severe SLE and organ damage. The aim of this PhD project was thus to increase the knowledge regarding ANA as well as aPL, and other potential biomarkers in relation to clinical features and disease outcomes in SLE.As expected, we found that the homogeneous ANA staining pattern was most common, and that it was associated with the occurrence of the ‘immunological disorder’ criterion. Speckled ANA was the second most common staining pattern, and it was inversely associated with arthritis, the ‘immunological disorder’ criterion and organ damage (Paper I). We also demonstrated that a considerable proportion of the patients lost ANA-positivity over time, whereas consistent staining patterns were most frequent (Paper V).Survival of patients with SLE has improved. Yet, in comparison to the general population, irreversible organ damage and increased mortality remains a critical concern. In Paper II, our cross-sectional analysis showed that more than a quarter of the patients had any aPL isotype (IgG, IgM or IgA class), and 14% were classified with antiphospholipid antibody syndrome (APS). A positive lupus anticoagulant (LA) test and/or IgG aPL tests were associated with most APS-related events and organ damage. Lupus nephritis, tobacco smoking, LA-positivity and the use of statins and/or corticosteroids were strongly associated with damage accrual, while hydroxychloroquine seemed to be protective. IgA aPL was not uncommon (16%) in Swedish cases of SLE, and analysis of IgA aPL may add information among clinically suspected APS-patients testing negative for LA and other aPL isotypes.Despite modern management and tax-funded health care with universal access, almost two thirds of the patients accrued organ damage over time, and the main causes of death were identified as malignancy, infection, and cardiovascular disease. We could confirm well established risk factors for organ damage such as APS, hypertension, and/or the use of corticosteroids, but we also observed that other factors such as pericarditis, haemolytic anaemia, lymphopenia and myositis seems to be of importance in this view (Paper IV).We also demonstrated that levels of the extracellular matrix protein osteopontin (OPN) was correlated with disease activity in patients with recent-onset SLE. In addition, OPN levels reflected global organ damage and were associated with APS and could have potential as a valuable biomarker in SLE (Paper III).Additional studies are warranted to further establish the clinical and mechanistic relevance of ANA seroconversion, OPN, as well as the importance of IgA aPL. Vigilance for malignancies, a restricted use of corticosteroids and prevention of cardiovascular disease and APS events are among modifiable factors to prevent organ damage and premature mortality.This thesis emphasizes the importance of autoantibodies in the pathogenesis, and diagnosis, of SLE. The autoantibody profile can be of great importance for tailored therapy in order to minimize the risk of organ damage accrual, morbidity as well as mortality.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Johansson, AG, et al.
(författare)
-
IgG immune complex binding to and activation of liver cells. An in vitro study with IgG immune complexes, Kupffer cells, sinusoidal endothelial cells and hepatocytes
- 2000
-
Ingår i: International Archives of Allergy and Immunology. - 1018-2438 .- 1423-0097. ; 121:4, s. 329-336
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: The aim was to study IgG immune complex (IC) binding to isolated hepatocytes, Kupffer cells (KCs) and sinusoidal endothelial cells (SECs). Further, we wished to analyze the capacity of IgG ICs to induce release of reactive oxygen metabolites by the IC-binding liver cells. Methods: ICs were formed between 125I-tyramine-cellobiose-labelled dinitrophenyl-conjugated human serum albumin (125I-TC-DNP10HSA) and polyclonal rabbit IgG antibodies. Binding of ICs to different rat liver cells in suspension was studied at 4░C. Production of reactive oxygen metabolites was measured by luminol-enhanced chemiluminescence at 37░C. Results: IgG mediated binding of 125I-TC-DNP10HSA to both KCs and SECs, but not to hepatocytes. The binding showed saturation kinetics and was blocked by an excess of unlabelled IgG-ICs. IgG-ICs activated KCs, but not SECs, to a chemiluminescence response. Conclusions: Both KCs and SECs bind IgG-ICs in vitro, probably via Fc receptor interaction. IgG-ICs activate KCs to produce reactive oxygen metabolites. The binding of IgG-ICs to isolated hepatocytes is small.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Reckner Olsson, Åsa, 1965-, et al.
(författare)
-
Aetiological factors of importance for the development of rheumatoid arthritis
- 2004
-
Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. ; 33:5, s. 300-306
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate exposure to external factors associated with risk or prevention of rheumatoid arthritis (RA).Methods: Two hundred and ninety‐three incident cases of RA and 1346 population‐based referents were included in a case‐referent study, in which previous exposure experiences were collected through a postal questionnaire.Results: An inverse association between RA and additional schooling after compulsory school was seen for men. Current smoking was associated with significantly increased risks of RA for men and women [odds ratio (OR) 2.9, 95% confidence interval (CI) 1.4–6.4, and OR 1.8, 95% CI 1.1–2.9, respectively], as was previous smoking for men (OR 2.3, 95% CI 1.2–4.4). There were also indications of relationships between previous use of a private well and RA in both men and women.Conclusion: Several previously published associations have been reproduced in the present study, which also generates some new hypotheses that suggest further research.
|
|
| 17. |
- Reckner Olsson, Åsa, 1965-, et al.
(författare)
-
Comorbidity and lifestyle, reproductive factors, and environmental exposures associated with rheumatoid arthritis
- 2001
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 60:10, s. 934-939
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate the influence of lifestyle, reproduction, and some external factors on the development of rheumatoid arthritis (RA) and to describe its comorbidity.METHODS Cases were identified retrospectively from 1980 to 1995 at the University Hospital in Linköping, Sweden. The study comprised 422 cases and 859 randomly selected population referents. Data on possible aetiological factors and comorbidity were collected by postal questionnaire.RESULTS The response rates were 67% among cases and 59% among referents. A decrease in the occurrence of atopic allergy was seen in the cases (odds ratio (OR) 0.6, 95% confidence interval (CI) 0.4 to 1.0). There was a positive association between RA and insulin treatment (OR 10.2, 95% CI 1.7 to 60.8) in women, and women with a short fertile period had an increased risk of RA (OR 2.5, 95% CI 1.1 to 5.4). Current and previous smoking were associated with increased risks for RA in both sexes, and in men a dose-response relationship was found with number of tobacco pack years (p for trend <0.005). The risk for RA decreased with increasing level of education in both men and women. Increased risks were seen in men born into households with private wells (OR 2.8, 95% CI 1.5 to 5.2), residentially exposed to mould (OR 4.6, 95% CI 1.1 to 20.2), or exposed to farm animals (OR 3.3, 95% CI 0.7 to 16.6). In women there were positive associations between RA and reporting a previous joint injury (OR 2.5, 95% CI 1.0 to 6.6) and prolonged exposure to hair dyes (OR 1.9, 95% CI 0.8 to 4.5).CONCLUSIONS RA, a disease with features of T helper 1 (Th1) dominated immune response, was inversely associated with atopic allergy, a Th2 dominated condition, while there were indications of a strong positive association with Th1 related diabetes mellitus. The results support a causal relationship between smoking and RA. The level of education was inversely associated with RA, while there was a positive association between RA and certain residential factors in men and a short fertile period in women.
|
|
| 18. |
- Reckner Olsson, Åsa, 1965-, et al.
(författare)
-
Occupations and exposures in the work environment as determinants for rheumatoid arthritis
- 2004
-
Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 61:3, s. 233-238
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Several occupational categories have been associated with rheumatoid arthritis (RA); this study was conducted to further evaluate these associations.Methods: Lifelong occupational history together with exposure experiences were collected through a postal questionnaire answered by 293 incident cases and 1346 population based referents. Occupational determinants were evaluated through stratified and multivariate analyses; pooled analyses with previously gathered data on 422 prevalent cases and 858 referents were also performed.Results: In both materials, significantly increased logistic odds ratios (LORs) were seen for male conductors, freight and transport workers (LOR 17.8, 95% CI 1.5 to 207.8 and LOR 4.7, 95% CI 1.4 to 16.3, respectively), and farmers and farm workers (LOR 2.4, 95% CI 1.1 to 5.2, and LOR 2.2, 95% CI 1.3 to 3.5, respectively). Among women, increased LORs were seen in the separate and the pooled material for printmakers and process engravers (LOR 5.5, 95% CI 0.9 to 32.6, and LOR 3.0, 95% CI 0.9 to 10.3, respectively). Increased risks were seen in both materials for men exposed to asbestos (LOR 2.5, 95% CI 1.0 to 6.8, and LOR 1.6, 95% CI 0.8 to 3.3, respectively), and vibrations (LOR 2.0, 95% CI 0.9 to 4.4, and LOR 2.2, 95% CI 1.3 to 3.8, respectively). The risk for RA increased with increasing duration of exposure to vibrations and mineral dust, respectively.Conclusions: There was evidence of a causal relation between exposures to vibrations and mineral dust and development of RA among men. Occupational factors seem to be aetiologically more important for men, and most occupations at risk involve multiple exposures. Several exposures associated with an increased risk for RA are frequent among farmers, and some of the occupations at risk include exposure to organic dust.
|
|
| 19. |
- Reckner, Åsa, 1965-, et al.
(författare)
-
Occupational determinants for rheumatoid arthritis
- 2000
-
Ingår i: Scandinavian Journal of Work, Environment and Health. - : Scandinavian Journal of Work, Environment and Health. - 0355-3140 .- 1795-990X. ; 26:3, s. 243-249
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of the present study was to evaluate possible occupational determinants for rheumatoid arthritis according to lifetime occupational history.Methods The cases were identified retrospectively from 1980 to 1995 at the University Hospital in Linköping, Sweden. The study comprised 422 cases and 859 randomly selected referents. Exposure data were collected through a postal questionnaire.Results For men, occupations with increased, although nonsignificant, odds ratios (OR) were farmers or farm workers [OR 1.8, 95% confidence interval (95% CI) 1.0-3.5], textile workers (OR 2.0, 95% CI 0.3-16.2), asphalters (OR 14.0, 95% CI 1.2-799.0 without latency requirement), and employees at service stations (OR 2.2, 95% CI 0.5-9.5). Among the women, hairdressers and beauticians (OR 2.7, 95% CI 0.8-8.6) had an increased risk for rheumatoid arthritis, as well as those exposed to hairdressing chemicals (OR 3.0, 95% CI 1.0-9.4) and meat products (OR 2.0, 95% CI 1.0-4.0).Conclusion Several of the findings in this study are in accordance with those of previous studies. The increased risks of rheumatoid arthritis for asphalters and employees at service stations are however new associations previously not described in the literature.
|
|
| 20. |
- Rydén, Ingvar, et al.
(författare)
-
Fucosylation of α1-acid glycoprotein (orosomucoid) compared with traditional biochemical markers of inflammation in recent onset rheumatoid arthritis
- 2002
-
Ingår i: Clinica Chimica Acta. - 0009-8981 .- 1873-3492. ; 317:1-2, s. 221-229
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Fucosylation of α1-acid glycoprotein (AGP, orosomucoid) has previously been found to be increased in patients with rheumatoid arthritis. Furthermore, the degree of fucosylation has been suggested to reflect disease activity. Therefore, we investigated the fucosylation of AGP in 131 patients (96 women and 35 men) with recent onset rheumatoid arthritis (RA). We compared the results with traditional biochemical markers of inflammation, i.e. plasma concentrations of AGP (P-AGP), and C-reactive protein (P-CRP).Methods: AGP fucosylation measured with a novel lectin enzyme-linked immunosorbent assay (ELISA) was compared with a disease activity score (DAS28) and its components, and with P-AGP, and P-CRP at the time of diagnosis, and at a follow-up visit 1 year later.Results: Both men and women with RA had increased AGP fucosylation compared to healthy individuals. We found a weak correlation between AGP fucosylation and DAS28 only in men. In men with initially increased AGP fucosylation, the level of fucosylation correlated with the change in DAS28 during the first year following diagnosis. Conclusion: We conclude that AGP fucosylation is not superior to traditional markers of disease activity in RA. However, AGP fucosylation may give some additional information to traditional biochemical markers on the disease progression in men.
|
|
| 21. |
|
|
| 22. |
- Samuelsson, A-K, et al.
(författare)
-
Evaluation of anti-hsp70 antibody screening in sudden deafness
- 2003
-
Ingår i: Ear and Hearing. - 0196-0202 .- 1538-4667. ; 24:3, s. 233-235
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the diagnostic utility of anti-hsp70 antibody screening in sudden deafness. Design: Sera from 27 patients with sudden deafness and 100 healthy blood donors were analyzed by Western blotting (WB) for the presence of antibodies against 68 kD heat shock protein (anti-hsp70). Results: 19% of the patient sera and 14% of the control sera turned out positive, which was not significantly different. Conclusions: The anti-hsp70 WB test lacks clinical utility for diagnostic screening in patients with sudden deafness.
|
|
| 23. |
- Sjöwall, Christopher, 1975-, et al.
(författare)
-
Abnormal Antinuclear Antibody Titers Are Less Common Than Generally Assumed in Established Cases of Systemic Lupus Erythematosus
- 2008
-
Ingår i: Journal of Rheumatology. - 0315-162X .- 1499-2752. ; 35, s. 1994-2000
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate antinuclear antibody (ANA) tests in established cases of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) by indirect immunofluorescence microscopy (F-ANA) and enzyme-immunoassays detecting antinucleosomal antibodies (ANSA-EIA). METHODS: Sera from 50 patients with SLE and 65 patients with RA were analyzed regarding abnormal concentrations of F-ANA (serum dilution >/= 1:200 = 95th percentile among 300 healthy blood donors). The sera were also analyzed with 2 commercial ANSA-EIA kits. RESULTS: An abnormal F-ANA titer occurred in 76% of the SLE sera compared to 23% in RA, and was not related to present use of antirheumatic drugs. At dilution 1:50, 84% of the SLE sera were F-ANA-positive compared to 20% of healthy women. Forty percent and 56%, respectively, of the SLE sera tested positive in the 2 ANSA-EIA kits. By the most sensitive assay, 96% of the ANSA-positive SLE sera produced a homogenous (chromosomal) F-ANA staining pattern compared to 18% of the ANSA-negative SLE sera. Ten of the 15 F-ANA-positive RA sera (63%) generated homogenous F-ANA staining and 13 (20%) tested positive in the most sensitive ANSA-EIA, but with no correlation to the F-ANA staining pattern. CONCLUSION: The sensitivity of F-ANA at an abnormal titer was surprisingly low (76%) in established cases of SLE. ANSA occurred in 56% of the SLE sera, but also in a fair number (20%) of RA sera. Practically all ANSA-positive SLE sera were identified by chromosomal F-ANA staining. We conclude that the antigen-specific antinucleosomal EIA does not have high enough diagnostic specificity to justify use of this analysis for routine diagnostic purposes.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Skogh, Thomas, 1952-
(författare)
-
Does a positive anti-CCP test identify a distinct arthritis entity?
- 2005
-
Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6354. ; 7:6, s. 230-232
-
Tidskriftsartikel (refereegranskat)abstract
- The introduction of tests recognizing 'anti-citrullinated protein antibodies' (ACPA) has caused a revolution in rheumatology. Immunization against citrullinated proteins is a feature almost unique for rheumatoid arthritis, although ACPA may occur long before the onset of symptoms. Even if the presence of ACPA does not seem to reveal a distinct arthritis phenotype at symptom onset, it predicts an aggressive disease course with unfavourable outcome. Despite the very high diagnostic specificity for rheumatoid arthritis, ACPA-positivity does not always accord with a traditional diagnosis of rheumatoid arthritis at clinical presentation. However, even when these patients are judged to suffer from mild undifferentiated arthritis, they call for follow-up and special attention by rheumatologists. © 2005 BioMed Central Ltd.
|
|
| 27. |
|
|
| 28. |
- Skoglund, Caroline, 1981-, et al.
(författare)
-
C-reactive protein and C1q regulate platelet adhesion and activation on adsorbed immunoglobulin G and albumin.
- 2008
-
Ingår i: Immunology and cell biology. - : Wiley. - 0818-9641 .- 1440-1711. ; 86:5, s. 466-74
-
Tidskriftsartikel (refereegranskat)abstract
- Blood platelets and C-reactive protein (CRP) are both used clinically as markers of ongoing inflammation, and both participate actively in inflammatory responses, although the biological effects are still incompletely understood. Rapidly adhering platelets express receptors for complement factor 1q (C1q) and the Fc part of immunoglobulin G (IgG), and CRP is known to activate/regulate complement via C1q binding, and to ligate FcgammaRs. In the present study, we used normal human IgG pre-adsorbed to a well-characterized methylated surface as a model solid-phase immune complex when investigating the effects of CRP and C1q on platelet adhesion and activation. Protein adsorption was characterized using ellipsometry and polyclonal antibodies, and human serum albumin (HSA) and non-coated surfaces were used as reference surfaces. Platelet adhesion to IgG and HSA was inhibited by both C1q and CRP. Furthermore, CRP (moderately) and C1q (markedly) decreased the spreading of adhering platelets. The combination of C1q and CRP was slightly more potent in reducing cell adhesion to IgG, and also impaired the adhesion to HSA and non-coated surfaces. Platelet production of thromboxane B2 (TXB(2)) was also reduced by C1q both in the presence and absence of CRP, whereas CRP alone had no effect on TXB(2) production. We conclude that CRP and C1q regulate the behaviour of platelets, and that this may be an important immunoregulatory mechanism during inflammatory conditions.
|
|
| 29. |
- Skoglund, Caroline, 1981-, et al.
(författare)
-
C-reactive protein inhibit complement-mediated platelet activation suggesting a protective role in atherogenesis
- 2006
-
Ingår i: Atherosclerosis Supplements. - Clare, Ireland : Elsevier. - 1567-5688 .- 1878-5050. ; 7:3, s. 284-284
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objective: C-reactive protein (CRP) represents a powerful predictor of coro- nary artery disease. However, its physiological role is not fully understood. The binding of CRP to its ligand phosphorylcholine (PC) activates the com- plement system via the classical pathway, although limited to the initial stages, i.e. no membrane attack complex is formed. The aim of this study was to chaxacterize CRP-induced complement activation on PC-coated surfaces, and to investigate the regulatory effects of PC-bound crp on complement induced platelet activation.Methods: PC conjugated to keyhole limpet hemocyanin was immobilized to cross-linked fibrinogen on silica particles. Ellipsometry and polyclonal anti- bodies were used to quantify deposition of serum proteins, complement factors and CRP on the surfaces. Washed platelets as well as serum were prepared according to standard protocols. CRP concentrations were measured with a high sensitivity assay. Lumi-aggregometry was used to evaluate the effects of PC-coated particles and CRP on complement-induced platelet aggregation and secretion.Results: Serum (5%) induced platelet aggregation and secretion through complement-dependent mechanisms. PC-coated particles antagonized the complement-mediated platelet activation but only if CRP was present. Inter- estingly, we found that a minor elevation of CRR below 5 rag/1 was sufficient to inhibit platelet activation.Conclusions: We suggest that CRP bound to PC-expressing ligands, e.g. bacteria or modified low-density lipoproteins in an atherosclerotic lesion, modulate complement activation and thereby prevent a harmful platelet activation.
|
|
| 30. |
- Svärd, Anna, et al.
(författare)
-
Presence and utility of IgA-class antibodies to cyclic citrullinated peptides in early rheumatoid arthritis : the Swedish TIRA project
- 2008
-
Ingår i: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 10:4
-
Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe present study was carried out to assess whether IgA-class antibodies against cyclic citrullinated peptides (IgA anti-CCP) in recent-onset rheumatoid arthritis add diagnostic and/or prognostic information to IgG anti-CCP analysis.MethodsSerum samples were obtained from 228 patients with recent-onset (<12 months) rheumatoid arthritis at the time of inclusion in the Swedish TIRA cohort (Swedish Early Intervention in Rheumatoid Arthritis). Sera from 72 of these patients were also available at the 3-year follow-up. Disease activity and functional ability measures (erythrocyte sedimentation rate, serum C-reactive protein, 28-joint count Disease Activity Score, physician's assessment of disease activity, and the Swedish version of the Health Assessment Questionnaire) were registered at inclusion and at regular follow-ups during 3 years. An IgA anti-CCP assay was developed based on the commercially available IgG-specific enzyme immunoassay from EuroDiagnostica (Arnhem, the Netherlands), replacing the detection antibody by an anti-human-IgA antibody. A positive IgA anti-CCP test was defined by the 99th percentile among healthy blood donors.ResultsAt baseline, a positive IgA anti-CCP test was observed in 29% of the patient sera, all of which also tested positive for IgG anti-CCP at a higher average level than sera containing IgG anti-CCP alone. The IgA anti-CCP-positive patients had significantly higher disease activity over time compared with the IgA anti-CCP-negative patients. After considering the IgG anti-CCP level, the disease activity also tended to be higher in the IgA anti-CCP-positive cases – although this difference did not reach statistical significance. The proportion of IgA anti-CCP-positive patients was significantly larger among smokers than among nonsmokers.ConclusionAnti-CCP antibodies of the IgA class were found in about one-third of patients with recent-onset rheumatoid arthritis, all of whom also had IgG anti-CCP. The occurrence of IgA-class antibodies was associated with smoking, and IgA anti-CCP-positive patients had a more severe disease course over 3 years compared with IgA anti-CCP-negative cases. Although IgA anti-CCP analysis does not seem to offer any diagnostic information in addition to IgG anti-CCP analysis, further efforts are justified to investigate the prognostic implications.
|
|
| 31. |
|
|
| 32. |
- Weile, B, et al.
(författare)
-
High prevalence rates of adult silent coeliac disease, as seen in Sweden, must be expected in Denmark
- 2001
-
Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - 0903-4641 .- 1600-0463. ; 109:11, s. 745-750
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To disclose the prevalence of adult "silent" coeliac disease in Denmark and Sweden. Experimental design: 1573 Danish and 1866 Swedish healthy blood donors were screened for the presence of serum anti-gliadin antibodies (AGA) by enzyme-linked immunosorbent assay. AGA-positive serum samples were further analysed for IgA anti-endomysium antibodies (EmA) by indirect immunofluorescence microscopy. Main results: The Danish donor population had a higher mean age than the Swedish (41.4 years versus 37.6 years) and a higher proportion of females (41% versus 32%), and had a lower mean level of AGA (17.3 units versus 20.6 units). Sixty-one (3.9%) Danish donors had AGA above the cut-off limit, and four of these also had positive EmA tests. Sixty (3.2%) Swedish donors had AGA above the cut-off limit, and five of these also had positive EmA. Coeliac pathology was proven by biopsy in all five coeliac disease-suspected Swedish donors. No small intestinal biopsy was performed in the coeliac disease-suspected Danish donors. Conclusions: Based upon the finding of EmA in AGA-positive serum samples, silent coeliac disease may be suspected in 1 per 394 Danish blood donors (2.5 per 1,000). A similar rate was proven in 1 per 373 Swedish blood donors (2.7 per 1,000), indicating no major differences in the prevalence of adult silent coeliac disease between the two neighbouring countries.
|
|
| 33. |
- Wirestam, Lina, 1986-
(författare)
-
Biomarkers of disease activity and organ damage in systemic lupus erythematosus
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systemic lupus erythematosus (SLE) is a systemic inflammatory disease. Clinically, the distinction between ongoing inflammation attributed to SLE, and organ damage due to medication or co-morbidities remains challenging. In addition, SLE is a heterogeneous disease where the various disease phenotypes complicate the search for biomarkers that adequately reflect disease activity and/or signs of increasing organ damage. The aim of the thesis was to investigate and evaluate potential new biomarkers of disease activity and/or organ damage in SLE patients.High mobility group box protein-1 (HMGB1) is a nuclear non-histone protein that can shuttle to the cytoplasm, become secreted extracellularly, and participate in systemic inflammation. Administration of monoclonal anti-HMGB1 antibodies has been reported both to attenuate and intensify disease in animal models of arthritis and lupus. In Paper I of the thesis, circulating anti-HMGB1 was found in 23% of the SLE patients and correlated with disease activity variables. The biological role of these autoantibodies remains to be elucidated.As a consequence of massive circulating levels of cellular debris and immune complexes, SLE patients have insufficient capacity to remove such material via the reticuloendothelial system. Pentraxin 3 (PTX3) may possibly protect against lupus flares due to classical complement activation, opsonization of apoptotic cells, and cytokine induction. In Paper II, circulating PTX3 was found to be inhibited or exhausted by interferon (IFN)-α, a key cytokine of SLE pathogenesis, and serum levels of PTX3 in SLE patients were inversely related to IFN-α levels. Suppressed PTX3 levels may contribute to a vicious circle resulting in impaired waste clearance, autoantigen exposure and autoantibody production, and sustained disease activity.Osteopontin (OPN), a protein known to influence cell signaling and apoptosis, has been proposed as a marker of organ damage in pediatric lupus. In a Swedish cross-sectional study, circulating OPN levels were found to be raised in SLE (Paper III). In patients with recent-onset disease, OPN reflected disease activity, while in established disease, OPN appeared to mirror damage accrual and cardiovascular damage. In Paper IV, OPN was instead analyzed in an international longitudinal multi-center study based on patients with recent-onset SLE and follow-up data. OPN turned out to be a poor predictor of organ damage, but significant associations were observed between OPN and disease activity both at disease onset, as well as over 5 years of follow-up.In conclusion, increased anti-HMGB1 antibody and decreased PTX3 levels could potentially sustain the impaired waste-disposal. Of the molecules analyzed in this thesis, OPN seems to be the best marker of disease activity. Further studies of these proteins may help to better understand SLE pathogenesis and to optimize treatment of patients.
|
|
| 34. |
- Wirestam, Lina, 1986-, et al.
(författare)
-
Osteopontin is associated with disease severity and antiphospholipid syndrome in well characterised Swedish cases of SLE
- 2017
-
Ingår i: Lupus Science and Medicine. - : BMJ Publishing Group Ltd. - 2053-8790. ; 4:1
-
Tidskriftsartikel (refereegranskat)abstract
- Objective The variety of disease phenotypes among patients with SLE challenges the identification of new biomarkers reflecting disease activity and/or organ damage. Osteopontin (OPN) is an extracellular matrix protein with immunomodulating properties. Although raised levels have been reported, the pathogenic implications and clinical utility of OPN as a biomarker in SLE are far from clear. Thus, the aim of this study was to characterise OPN in SLE.Methods Sera from 240 well-characterised adult SLE cases classified according to the American College of Rheumatology (ACR) and/or the Systemic Lupus International Collaborating Clinics (SLICC) criteria, and 240 population-based controls were immunoassayed for OPN. The SLE Disease Activity Index 2000 (SLEDAI-2K) was used to evaluate disease activity and the SLICC/ACR Damage Index (SDI) to detect damage accrual.Results Serum OPN levels were in average raised fourfold in SLE cases compared with the controls (p<0.0001). OPN correlated with SLEDAI-2K, especially in patients with a disease duration of <12 months (r=0.666, p=0.028). OPN was highly associated with SDI (p<0.0001), especially in the renal (p<0.0001), cardiovascular (p<0.0001) and malignancy (p=0.012) domains. Finally, OPN associated with coherent antiphospholipid syndrome (APS; p=0.009), and both clinical and laboratory criteria of APS had significant positive impact on OPN levels.Conclusions In this cross-sectional study, circulating OPN correlates with disease activity in recent-onset SLE, reflects global organ damage and associates with APS. Longitudinal studies to dissect whether serum OPN also precedes and predicts future organ damage are most warranted.
|
|
| 35. |
- Ziegelasch, Michael, 1966-
(författare)
-
Diagnostic and prognostic potential of joint imaging in patients with anti-citrullinated protein antibodies
- 2018
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The introduction of novel therapeutic strategies set new goals for the patients’ outcome, which aims to achieve remission. This goal requires early diagnosis of RA and prompt efficient pharmacotherapy. The introduction of anti-citrullinated protein antibodies (ACPA) two decades ago allowed an earlier RA diagnosis. However, there are indications that ACPA positivity is still associated with higher rates of radiographic damage. As the small joints in hands and feet commonly are the first involved sites of inflammation, the role of different imaging modalities were studied regarding their diagnostic and prognostic impact for assessment of arthritis in RA. Further, ultrasound (US) and radiography were used to study the association between RA-specific antibodies and the occurrence of arthritis and joint damage in systemic lupus erythematosus (SLE).The use of US allows assessment of soft tissue like joint capsules, tendons and bursae. Used for a live scanning, it is easy to detect effusions and edema. Doppler indicates vasoproliferation were inflammation is present. Also, US seems to be more sensitive than radiography to detect minimal structural changes located at bone surfaces. We wanted to investigate whether US findings in a pre-RA stage can predict development of arthritis.Digital X-ray radiogrammetry (DXR) is a technique based on computerized analyses of standard hand radiographs to calculate peripheral bone mineral density (BMD) of the three middle metacarpal bones (DXR-BMD). In order for early treatment decisions, we aimed to study whether changes in DXR-BMD loss after 3 months can predict radiographic damage in early RA.In conclusion, the studies showed that ACPA-positivity is still associated with a higher risk of radiographic damage regardless of early treatment decisions. Therefore, close radiographic monitoring and readiness to intensive treatment is warranted in ACPA-positive patients. This thesis also shows that erosions detected by US in ACPA-positive patients with arthralgia predict development of clinical arthritis. Also, the magnitude of DXR-BMD loss helps identify patients at higher risk for future radiographic damage, and may therefore help to improve early treatment decisions. Finally, US and radiography confirm a higher rate of arthritis and erosions also in SLE patients who are positive for RA-specific antibodies.
|
|
