| 1. |
- Amirahmadi, S. F., et al.
(författare)
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Arthritogenic anti-type II collagen antibodies are pathogenic for cartilage-derived chondrocytes independent of inflammatory cells
- 2005
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 52:6, s. 1897-1906
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Some monoclonal antibodies (mAb) to type II collagen (CII) are arthritogenic upon passive transfer to mice. We undertook this study to investigate whether such mAb are pathogenic in the absence of mediators of inflammation. METHODS: The arthritogenic mAb CIIC1 and M2139, and the nonarthritogenic mAb CIIF4, each reactive with a distinct and well-defined conformational epitope on CII, were compared with control mAb GAD6. Bovine chondrocytes were cultured with one of the mAb, and on days 3, 6, and 9, antibody binding by chondrocytes and newly synthesized extracellular matrix (ECM) was examined by immunofluorescence, morphologic effects were studied by electron microscopy, and synthesis of matrix components was determined by metabolic labeling with (3)H-proline for collagen and (35)S-sulfate for proteoglycans. RESULTS: All 3 mAb to CII bound to the matrix. CIIC1 and M2139 adversely affected the cultures, whereas CIIF4 did not. CIIC1 caused disorganization of CII fibrils in the ECM without affecting chondrocyte morphology, and increased matrix synthesis. M2139 caused thickening and aggregation of CII fibrils in the ECM and abnormal chondrocyte morphology but matrix synthesis was unaffected. CONCLUSION: The unique arthritogenic capacity of particular anti-CII mAb upon passive transfer could be explained by their adverse, albeit differing, effects in primary cultures of chondrocytes. Such effects occur independent of inflammation mediators and are related to the epitope specificity of the mAb. Interference with the structural integrity of CII could precede, and even initiate, the inflammatory expression of disease.
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| 2. |
- Bas, D. B., et al.
(författare)
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Collagen antibody-induced arthritis evokes persistent pain with spinal glial involvement and transient prostaglandin dependency
- 2012
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 64:12, s. 3886-3896
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivePain is one of the most debilitating symptoms reported by rheumatoid arthritis (RA) patients. While the collagen antibody–induced arthritis (CAIA) model is used for studying the effector phase of RA pathologic progression, it has not been evaluated as a model for studies of pain. Thus, this study was undertaken to examine pain-like behavior induced by anticollagen antibodies and to assess the effect of currently prescribed analgesics for RA. In addition, the involvement of spinal glia in antibody-induced pain was explored.MethodsCAIA was induced in mice by intravenous injection of a collagen antibody cocktail, followed by intraperitoneal injection of lipopolysaccharide. Disease severity was assessed by visual and histologic examination. Pain-like behavior and the antinociceptive effect of diclofenac, buprenorphine, gabapentin, pentoxifylline, and JNK-interacting protein 1 were examined in mechanical stimulation experiments. Spinal astrocyte and microglia reactivity were investigated by real-time polymerase chain reaction and immunohistochemistry.ResultsFollowing the induction of CAIA, mice developed transient joint inflammation. In contrast, pain-like behavior was observed prior to, and outlasted, the visual signs of arthritis. Whereas gabapentin and buprenorphine attenuated mechanical hypersensitivity during both the inflammatory and postinflammatory phases of arthritis, diclofenac was antinociceptive only during the inflammatory phase. Spinal astrocytes and microglia displayed time-dependent signs of activation, and inhibition of glial activity reversed CAIA-induced mechanical hypersensitivity.ConclusionCAIA represents a multifaceted model for studies exploring the mechanisms of pain induced by inflammation in the articular joint. Our findings of a time-dependent prostaglandin and spinal glial contribution to antibody-induced pain highlight the importance of using appropriate disease models to assess joint-related pain.
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| 3. |
- Bergman, Stefan, 1959-, et al.
(författare)
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Lifestyle factors were seldom discussed with patients visiting a rheumatology clinic
- 2013
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Ingår i: Arthritis and Rheumatism. - Hoboken, NJ : John Wiley & Sons. - 0004-3591 .- 1529-0131. ; 65:Special issue, Supplement 10, s. S982-S983, Meeting Abstract: 2307
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Tidskriftsartikel (refereegranskat)abstract
- Background/Purpose: There is increasing evidence that lifestyle factors are of importance for outcome of rheumatic diseases, and lifestyle interventions should be a natural part of management.The aim was to study if lifestyle factors (diet, physical activity, smoking and alcohol use) were discussed with patients on a regular visit to a specialized rheumatology clinic.Methods: A questionnaire was distributed to 318 patients visiting an outpatient clinic, and 223 (70%) responded. The questionnaire assessed if lifestyle factors (diet, physical activity, smoking and alcohol use) were discussed at the visit. If not, it also assessed if the patients themselves felt that this discussion would have been desirable.Results: The questionnaire was answered by 69 (31%) men and 154 (69%) women, and 69% were younger than 65 years. Diet was more frequently discussed with men (14.7% vs. 4.8%) although more women (11.6% vs 4.4%) would have desired it to be discussed. 83% of the patients did not consider that it was needed to discuss at all. Physical activity was discussed with 28% of the patients, without any significant difference between men and women. Only 8% of those not having this discussion thought that they needed it. Smoking was discussed with 15%, without any significant difference between men and women. Alcohol use was discussed with more men than women (15.9% vs. 4.0%). Of those not having this discussion 3% of the women but none of the men thought that they needed it.Conclusion: Although recommended as part of management, lifestyle factors are seldom discussed with the patients, and this discussion is not actively thought for by the patients. Lifestyle factors are more frequently discussed with men although women would have desired to have this discussion to a higher extent. There is a need for health care to actively take the initiative and discuss lifestyle as part of regular care.
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| 4. |
- Bremander, Ann, 1957-, et al.
(författare)
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Smoking Is Associated with Worse and More Widespread Pain, Worse Disease Activity, Function, Fatigue and Health Related Quality of Life in Patients with Axial Spondyloarthritis : Results From a Population Based Cohort
- 2012
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Ingår i: Arthritis and Rheumatism. - Hoboken, NJ : John Wiley & Sons. - 0004-3591 .- 1529-0131. ; 64:S10, s. S43-S43
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Tidskriftsartikel (refereegranskat)abstract
- Background: In subjects with early axial Spondyloarthritis (SpA) smoking has recently been associated with earlier onset of disease, worse lesions of the sacroiliac joints and in later stages syndesmophyte progression. The aim was to study associations of smoking habits with self-reported information in a large population based cohort of patients with axial SpA.Methods: A cross-sectional questionnaire survey performed in 2009 included all health care seeking subjects aged >18 years with a diagnosis of SpA according to ICD 10 codes identified by a regional health care register (n=3711). Smoking habits were studied in patients with ankylosing spondylitis (AS, ICD M45) and in patients who fulfilled criteria for “non AS axial SpA” (without having one of AS). Criteria for non AS axial SpA were based on data from the questionnaire: pain for 3 months or more during the last 12 months together with 2 or more features out of 5 (inflammatory back pain, history of psoriasis, uveitis/tendinitis, inflammatory bowel disease or heredity). The questionnaire included data on smoking (never smokers vs. ever smokers), disease activity (BASDAI) physical function (BASFI), general health (BAS-G) all measured with numerical rating scales 0-10 (best to worst), health related quality of life (EQ-5D, 0-1 worst to best), pain, fatigue (numerical rating scales 0-10 best to worst) and number of painful regions noted on a pain mannequin (0-16 best to worst). Linear regression analysis was performed and all data were controlled for sex and age.Results: Response rate was 76% whereof 2167 (58%) returned the questionnaire and 18% declined participation in the study. 598 subjects had an AS diagnose and 572 fulfilled the criteria for non AS axial SpA.The AS group had a mean age of 54 (SD14) years and 35% were women. Never smokers constituted 48% of the AS group. Ever smokers had worse scores in all studied variables compared with never smokers.The linear regression analysis showed that ever smokers in the AS group had worse self-reported scores in BASDAI with age-sex adjusted parameter estimate (B) = 0.60 (95% CI 0.21 ; 1.00), BASFI B = 0.51 (95% CI 0.11 ; 0.91) and fatigue B = 0.51 (95% CI 0.06 ; 1.00) . There was a tendency to worse scores for ever smokers also in EQ-5D B = -0.04 (95% CI -0.09 ; 0.001)Mean age in the non AS axial SpA group was 55 (SD 14) years and 68% were women. Never smokers constituted 38% of this group. Also in the non AS axial SpA group the linear regression analysis showed that ever smokers had worse self-reported scores in BASDAI with age-sex adjusted parameter estimate (B) = 0.59 (95% CI 0.23 ; 0.94), BASFI B = 0.59 (95% CI 0.17 ; 1.00), pain B = 0.45 (95% CI 0.08 ; 0.82) and fatigue B = 0.43 (95% CI 0.03 ; 0.83), no of painful areas B = 0.73 (95% CI 0.06 ; 1.46) and also in EQ-5D B = -0.06 (95% CI -0.11 ; -0.002). Conclusion: In a large population based axial SpA cohort, both patients with AS and non AS axial SpA who were ever smokers reported worse clinical features compared with never smokers. Further longitudinal studies are needed to better understand cause and effect. However, smoking cessation should be recommended not only due to general health perspectives but also due to disease specific issues.References1Smokers in early axial spondyloarthritis have earlier disease onset, more disease activity, inflammation and damage, and poorer function and health-related quality of life: results from the DESIR cohort. Chung HY, Machado P, van der Heijde D, D'Agostino MA, Dougados M. Ann Rheum Dis. 2012 Jun;71(6):809-16.
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| 5. |
- Bremander, Ann, 1957-, et al.
(författare)
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Smoking is Associated with Worse and More Widespread Pain, Worse Fatigue, General Health and Quality of Life in a Swedish population Based Cohort of Patients with Psoriatic Arthritis
- 2012
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Ingår i: Arthritis and Rheumatism. - Hoboken, NJ : John Wiley & Sons. - 0004-3591 .- 1529-0131. ; 64:S10, s. S777-S778
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Tidskriftsartikel (refereegranskat)abstract
- Background/Purpose: Smoking has been found to be associated with an increased risk of developing psoriatic arthritis (PsA)1. The purpose of this study was analyse possible associations of smoking habits with self-reported clinical features in a large population based cohort of patients with a diagnosis of PsA.Methods: All health care seeking subjects with a diagnose of PsA according to ICD 10 codes (given at least once by a rheumatologist/internist or twice by any other physician) were identified by a regional health care register during 2003-20072. In 2009 all identified subjects aged 18 years or older (n=2003) were invited to participate in a cross sectional questionnaire survey. The questionnaire included self-reported data on smoking (never smokers or ever smokers), age at disease onset, physical function (HAQ, 0-3 best to worst), pain, fatigue and global health (numerical rating scales 0-10 best to worst) health related quality of life (EQ-5D, 0-1 worst to best), and number of painful regions noted on a pain mannequin (0-16, best to worst). Linear regression analysis was performed and all data were controlled for sex and age.Results: Response rate was 77% whereof 369 patients (18%) declined participation and 1185 (59%) returned the questionnaire, mean age 57.5 (SD 13.5) years and 58% were women. 1173 subjects responded to the smoking question whereof 448 (38%) were never smokers and 725 (62%) were ever smokers. Mean age at disease onset was 42.3 (SD 13.4) years in never smokers vs. 46.0 (SD 13.2) in ever smokers. Never smokers vs. ever smokers had mean HAQ 0.59 (SD 0.6) vs. 0.71 (SD 0.6), mean pain 3.9 (SD 2.4) vs.4.4 (SD 2.5), mean fatigue 4.4 (SD 2.8) vs. 5.0 (SD 2.7), mean global health 3.9 (SD 2.4) vs. 4.4 (SD 2.3), mean EQ-5D 0.68 (SD 0.23) vs. 0.63 (SD 0.26) and mean no of painful regions were 7.2 (SD 4.0) vs. 7.9 (SD 4.3).The regression analysis showed that ever smokers had worse pain with age-sex adjusted parameter estimates (B) = 0.38 (95% CI 0.09 ; 0.67), worse fatigue B = 0.34 (95% CI 0.02 ; 0.66), worse global health B = 0.36 (95% CI 0.09 ; 0.64), worse EQ-5D B = -0.04 (95% CI -0.07 ; -0.01) and an increased no of painful regions B = 0.54 (95% CI 0.02 ; 1.07) compared with never smokers.Conclusion: In this population based PsA cohort, patients who were ever smokers reported worse clinical features compared with never smokers. Further longitudinal studies are needed to better understand cause and effect. However, smoking cessation should be recommended due to general health perspectives and also due to disease specific issues.
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| 6. |
- Bremander, Ann, et al.
(författare)
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Validation of the Rheumatoid and Arthritis Outcome Score (RAOS) for the lower extremity
- 2003
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Ingår i: Health and Quality of Life Outcomes. - : Springer Science and Business Media LLC. - 1477-7525. ; 48:9 Suppl. S, s. 687-687
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with inflammatory joint diseases tend due to new treatments to be more physically active; something not taken into account by currently used outcome measures. The Rheumatoid and Arthritis Outcome Score (RAOS) is an adaptation of the Knee injury and Osteoarthritis Outcome Score (KOOS) and evaluates functional limitations of importance to physically active people with inflammatory joint diseases and problems from the lower extremities. The aim of the study was to test the RAOS for validity, reliability and responsiveness. METHODS: 119 in-patients with inflammatory joint disease (51% RA) admitted to multidisciplinary care, mean age 56 (+/-13), 73% women, mean disease duration 18 (+/-14) yr were consecutively enrolled. They all received the RAOS, the SF-36, the HAQ and four subscales of the AIMS2 twice during their stay for test of validity and responsiveness. Test-retest reliability of the RAOS questionnaire was calculated on 52 patients using the first or second administration and an additional mailed questionnaire. RESULTS: The RAOS met set criteria of reliability and validity. The random intraclass correlation coefficient (ICC 2,1) for the five subscales ranged from 0.76 to 0.92, indicating that individual comparisons were possible except for the subscale Sport and Recreation Function. Inter-item correlation measured by Cronbach's alpha ranged from 0.78 to 0.95. When measuring construct validity the highest correlations occurred between subscales intended to measure similar constructs. Change over time (24 (+/- 7) days) due to multidisciplinary care was significant for all subscales (p < 0.001). The effect sizes ranged from 0.30-0.44 and were considered small to medium. All the RAOS subscales were more responsive than the HAQ. Some of the SF-36 subscales and the AIMS2 subscales were more responsive than the RAOS subscales. CONCLUSION: It is possible to adapt already existing outcome measures to assess other groups with musculoskeletal difficulties in the lower extremity. The RAOS is a reliable, valid and responsive outcome instrument for assessment of multidisciplinary care. To fully validate the RAOS further studies are needed in other populations.
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| 7. |
- Brodin, N., et al.
(författare)
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Coaching patients with early rheumatoid arthritis to healthy physical activity : A multicenter, randomized, controlled study
- 2008
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Ingår i: Arthritis and Rheumatism. - Hoboken, NJ : Wiley. - 0004-3591 .- 1529-0131. ; 59:3, s. 325-331
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate the effect of a 1-year coaching program for healthy physical activity on perceived health status, body function, and activity limitation in patients with early rheumatoid arthritis. Methods. A total of 228 patients (169 women, 59 men, mean age 55 years, mean time since diagnosis 21 months) were randomized to 2 groups after assessments with the EuroQol visual analog scale (VAS), Grippit, Timed-Stands Test, Escola Paulista de Medicina Range of Motion scale, walking in a figure-of-8, a visual analog scale for pain, the Health Assessment Questionnaire disability index, a self-reported physical activity questionnaire, and the Disease Activity Score in 28 joints. All patients were regularly seen by rheumatologists and underwent rehabilitation as prescribed. Those in the intervention group were further individually coached by a physical therapist to reach or maintain healthy physical activity (=30 minutes, moderately intensive activity, most days of the week). Results. The retention rates after 1 year were 82% in the intervention group and 85% in the control group. The percentages of individuals in the intervention and control groups fulfilling the requirements for healthy physical activity were similar before (47% versus 51%, P > 0.05) and after (54% versus 44%, P > 0.05) the intervention. Analyses of outcome variables indicated improvements in the intervention group over the control group in the EuroQol VAS (P = 0.025) and muscle strength (Timed-Stands Test, P = 0.000) (Grippit, P = 0.003), but not in any other variables assessed. Conclusion. A 1-year coaching program for healthy physical activity resulted in improved perceived health status and muscle strength, but the mechanisms remain unclear, as self-reported physical activity at healthy level did not change. © 2008, American College of Rheumatology.
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| 8. |
- Burkhardt, H., et al.
(författare)
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Epitope-specific recognition of type II collagen by rheumatoid arthritis antibodies is shared with recognition by antibodies that are arthritogenic in collagen-induced arthritis in the mouse
- 2002
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Ingår i: Arthritis & Rheumatology. - : Wiley. - 2326-5191 .- 2326-5205. ; 46:9, s. 2339-2348
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To analyze the fine specificity of IgG autoantibodies in sera from rheumatoid arthritis (RA) patients for type II collagen (CII) epitopes that are arthritogenic in collagen-induced arthritis (CIA), a relevant murine model of RA. METHODS: For enzyme-linked immunosorbent assay (ELISA) analysis of conformation-dependent autoantibody binding, recombinant chimeric collagens that harbor the respective CII epitopes as an insertion within the frame of a constant type X collagen triple helix were constructed. In addition, synthetic peptides mimicking the native collagen structures were applied for the first time in the ELISA assessment of humoral CII autoimmunity. RESULTS: The pathogenicity of IgG responses to certain CII determinants in CIA was demonstrated by arthritis development in BALB/c mice upon the combined transfer of 2 mouse monoclonal antibodies specific for precisely mapped conformational CII epitopes (amino acid residues 359-369 [C1(III)] and 551-564 [J1]), whereas antibodies to another epitope (F4) were not arthritogenic. To test whether human autoimmune responses are similarly directed to these conserved CII determinants, serum IgG was analyzed. The prevalence of sera with increased IgG binding to the C1(III) epitope was significantly higher in RA compared with sera from healthy donors or from patients with other rheumatic conditions, e.g., osteoarthritis (OA), systemic lupus erythematosus (SLE), or relapsing polychondritis (RP), whereas levels of antibodies specific for the nonarthritogenic F4 epitope were associated with OA rather than RA. CONCLUSION: Autoimmunity to CII, although detectable in different rheumatic conditions, differs in fine specificity between distinct disease entities. In RA, in contrast to degenerative joint disease, RP, and SLE, autoantibody responses are directed to an evolutionary conserved CII structure that is also targeted by pathogenic autoimmune responses in murine models of arthritis.
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| 9. |
- Carlsén, Stefan, et al.
(författare)
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Cartilage oligomeric matrix protein induction of chronic arthritis in mice
- 2008
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 58:7, s. 2000-2011
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To develop a new mouse model for arthritis using cartilage oligomeric matrix protein (COMP) and to study the role of major histocompatibility complex (MHC) and Ncf1 genes in COMP-induced arthritis (COMPIA). METHODS: Native (pentameric) and denatured (monomeric) COMP purified from a rat chondrosarcoma was injected into mice with Freund's adjuvant to induce arthritis. C3H.NB, C3H.Q, B10.P, B10.Q, (B10.Q x DBA/1)F1, (BALB/c x B10.Q)F1, Ncf1 mutated, H-2Aq, H-2Ap, and human DR4+-transgenic mice were used. Anti-COMP antibodies and COMP levels in the immune sera were analyzed, and passive transfer of arthritis with purified immune sera was tested. RESULTS: Immunization with rat COMP induced a severe, chronic, relapsing arthritis, with a female preponderance, in the mice. The disease developed in C3H.NB mice, but not in B10.P mice, although they share the same MHC haplotype. Both H-2q and H-2p MHC haplotypes allowed the initiation of COMPIA. Using H-2Aq-transgenic and H-2Ap-transgenic mice, we demonstrated a role of both the Aq and Ep class II molecules in this model. Interestingly, the introduction of a mutation in the Ncf1 gene, which is responsible for the reduced oxidative burst phenotype, into the COMPIA-resistant B10.Q mouse strain rendered them highly susceptible to arthritis. In addition, the transfer of anti-COMP serum was found to induce arthritis in naive mice. Mice transgenic for the rheumatoid arthritis (RA)-associated DR4 molecule were found to be highly susceptible to COMPIA. CONCLUSION: Using rat COMP, we have developed a new and unique mouse model of chronic arthritis that resembles RA. This model will be useful as an appropriate and alternative model for studying the pathogenesis of RA.
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| 10. |
- Croxford, Allyson M., et al.
(författare)
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Specific antibody protection of the extracellular cartilage matrix against collagen antibody-induced damage
- 2010
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Ingår i: Arthritis and Rheumatism. - Hoboken, NJ : John Wiley & Sons. - 0004-3591 .- 1529-0131. ; 62:11, s. 3374-3384
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The type II collagen (CII)-specific monoclonal antibodies (mAb) M2139 and CIIC1 induce arthritis in vivo and degrade bovine cartilage explants in vitro, whereas mAb CIIF4 is nonarthritogenic and prevents arthritis development when given in combination with M2139 and CIIC1. To determine the nature of the protective capacity of CIIF4 antibody, we examined the effects of adding CIIF4 to cartilage explants cultured in vitro with M2139 and CIIC1. METHODS: Bovine cartilage explants were cultured in the presence of M2139 and CIIC1, with or without CIIF4. Histologic changes were examined, and chemical changes to collagens and proteoglycans were assessed by Fourier transform infrared microspectroscopy (FTIRM). Fresh cartilage and cartilage that had been freeze-thawed to kill chondrocytes cultured with or without the addition of GM6001, a broad-spectrum inhibitor of matrix metalloproteinases (MMPs), were compared using FTIRM analysis. RESULTS: M2139 and CIIC1 caused progressive degradation of the cartilage surface and loss of CII, even in the absence of viable chondrocytes. CIIF4 did not cause cartilage damage, and when given with the arthritogenic mAb, it prevented their damage and permitted matrix regeneration, a process that required viable chondrocytes. Inhibition of MMP activity reduced cartilage damage but did not mimic the effects of CIIF4. CONCLUSION: CII-reactive antibodies can cause cartilage damage or can be protective in vivo and in vitro, depending on their epitope specificity. Since CII antibodies of similar specificity also occur in rheumatoid arthritis in humans, more detailed studies should unravel the regulatory mechanisms operating at the effector level of arthritis pathogenesis. © 2010 by the American College of Rheumatology.
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