Scandinavian Journal of Rheumatology最新文献

Objectives: In axial spondyloarthritis (axSpA), patient-perceived quality of life/global functioning and health (GH) can be assessed using disease-specific [Assessment of SpondyloArthrit is international Society Health Index (ASAS-HI)] or generic [(3-level EuroQol 5 Dimensions (EQ-5D-3L)] scores. Our objectives were to explore the link between these scores and to define thresholds for good and poor GH.

Method: We conducted a post-hoc analysis of the cross-sectional ASAS-PerSpA study for patients fulfilling ASAS criteria for axSpA. The ASAS-HI and EQ-5D scores were analysed visually (distribution, scatterplot) and through Spearman correlation and agreement (deciles). To determine cut-offs for good and poor GH on EQ-5D based on the validated ≤5 and ≥12 cut-offs for ASAS-HI, respectively, receiver operating characteristics (ROC) curves and distribution-based methods were applied. Validity was assessed using crude concordance and prevalence-adjusted bias-adjusted kappa; discordance between groups was explored.

Results: In 2651 patients (median age 41.0 years, 66.5% men), the correlation between ASAS-HI and EQ-5D was high (r = -0.73) and agreement (between deciles) was moderate (weighted kappa = 0.51). Both ROC areas under the curve were 0.86; thresholds of 0.69 and 0.54 for EQ-5D were chosen for good and poor GH, respectively. Crude concordances and agreement were satisfactory (0.80-0.81 and 0.60-0.61, respectively). The EQ-5D cut-off for good GH performed better than that for poor GH.

Conclusion: ASAS-HI and EQ-5D were highly correlated but did not fully overlap. We propose EQ-5D thresholds corresponding to the ASAS-HI thresholds for good and poor GH; however, caution is needed when assessing poor GH with EQ-5D. These findings will be useful to compare GH when only one of the outcome measures is available.

Objective: The north-south gradient hypothesis proposes that individuals with rheumatoid arthritis (RA) residing in southern regions manifest a younger age of onset and milder disease compared to their northern counterparts. This study aimed to compare treatment-naïve, new-onset RA patients in Denmark and Turkey, examining demographic, clinical, laboratory, and genetic parameters.

Method: Prospective data collection was conducted, with all patients meeting the 2010 American College of Rheumatology/European League Against Rheumatism criteria. Shared epitope (SE) allele carrier frequencies were examined for genetic comparisons between patients and normal controls.

Results: Out of 223 RA patients, 109 were Danish and 114 Turkish. Danish patients exhibited a median age at onset of 60 years, whereas Turkish patients were younger at 51 years (p = 0.0007). The Danish cohort displayed significantly more swollen and tender joints, resulting in higher Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP). Danish RA patients and controls possessed more RA risk-enhancing alleles (S2 + S3P) and fewer risk-protective (S1 + S3D) alleles than Turkish patients and controls.

Conclusion: This study substantiates the north-south gradient hypothesis, highlighting that new-onset RA patients in Denmark tend to experience an older age of onset and more severe disease activity than their Turkish counterparts. Variations in risk-enhancing alleles and fewer risk-protective alleles in Danish patients and controls are associated with these distinctions. Future research should investigate the genetic and environmental factors underlying these regional disparities, exploring their persistence in the long-term course of the disease through follow-up studies.

Objective: To investigate the function of mitophagy in instructing T-cell differentiation of patients with rheumatoid arthritis (RA).

Method: The mRNA and protein levels of optic atrophy protein-1 were detected in T cells from 94 RA patients and 37 age- and sex-matched healthy individuals by quantitative polymerase chain reaction and Western blotting. The impact of mitophagy on the differentiation of T cells was determined by flow cytometry. The therapeutic effect of targeting mitophagy was explored in humanized RA chimeras.

Results: Our study showed that T cells exerted high levels of mitophagy in RA patients. Since multiple T-cell subtypes play crucial roles in RA, we determined that mitophagy had a significant impact on the differentiation of tissue-resident memory T (Trm) cells, but not Th1 or Th17 cells. Importantly, we demonstrated that inhibiting mitophagy significantly reduced the number of Trm cells and downregulated inflammatory responses, as evidenced by diminished levels of T cell receptor β, interferon-γ, and interleukin-17A, in the humanized RA chimeras.

Conclusions: Mitophagy is elevated in RA T cells, leading to maldifferentiation of Trm cells in RA patients. Since these findings were obtained from clinical patients, mitophagy may be a potential therapeutic target for RA treatment.

Objectives: Rheumatoid arthritis (RA) is an autoimmune disease of the synovial joints. Pro-inflammatory cytokines produced by various immune cells drive the chronic inflammatory processes that lead to joint damage. Many drugs are available for the treatment of RA, but a significant proportion of patients do not respond adequately to them and/or have severe adverse effects. Accordingly, there is an urgent need for new therapeutics for RA. Therefore, we tested pristimerin, a natural triterpenoid, for its anti-arthritic activity in experimental RA.

Method: Collagen antibody-induced arthritis (CAIA) was induced in DBA/1 mice. After the onset of arthritis, mice were injected daily intraperitoneally with pristimerin or vehicle for 9 days. The severity of clinical arthritis was graded and further validated by micro-computed tomography and histological examination of the hind paws. Defined mediators of arthritogenic processes were quantified by gene expression in the spleen and further validated by immunohistochemistry of paws.

Results: We observed that pristimerin can effectively control arthritis progression in CAIA mice. A preliminary exploration of the mechanisms showed that pristimerin targeted key pro-inflammatory cytokines and chemokines, along with specific mediators of angiogenesis, bone remodelling, and cellular signalling, including the Notch signalling pathway.

Conclusions: This is the first report on pristimerin for its use in the treatment of antibody-induced arthritis and for the targeting of Notch pathway in arthritis by this triterpenoid. As pristimerin can control the effector phase of arthritis, our results are promising for the translation of this experimental therapy to RA patients.

Objective: We conducted a longitudinal observational study over 11 years to identify the risk factors for developing shoulder pain, stiffness, or both.

Method: The study population (n = 1645) was identified from Health 2000 Survey, a nationally representative sample of Finns aged ≥ 44 years, without shoulder pain and stiffness at the start of the study based on a questionnaire. The independent variables included age, sex, body mass index (BMI), education level, diabetes, physical work exposures, and Beck's depression score. We used multinomial logistic regression models to estimate relative risk ratios and 95% confidence intervals for three outcomes: shoulder pain, shoulder stiffness, and both combined.

Results: We found that excess body mass and depressive symptoms were shared statistically significant risk factors for all three outcomes. However, we also observed distinct risk factor profiles: older age was associated with lower risk of shoulder pain but higher risk for shoulder stiffness with or without pain, while females had a lower risk of shoulder stiffness with or without pain. Participants with diabetes had higher risk of shoulder stiffness only. Physical workload factors predicted an increased risk of the combination of shoulder pain and stiffness.

Conclusions: Our study identified increased BMI and depressive symptoms as consistent risk factors for shoulder pain, stiffness, or both. Older age increased the risk of shoulder stiffness but lowered the risk of pain alone, while females had a lower risk of stiffness. Diabetes was specifically linked to shoulder stiffness, and physical workload increased the risk of combined pain and stiffness.

Objective: Lung computed tomography (CT) is a valid method for the detection and assessment of the progression of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients. The objective of this study is to conduct a comparative analysis of the characteristics of individuals with RA-ILD, with and without radiographic progression, determined using lung CT scans.

Method: In this retrospective observational study, three radiologists re-evaluated CT scans of RA-ILD patients who had at least one follow-up CT. The lungs were divided into upper, middle, and lower zones, with equal slices. Progression was defined as the involvement of more zones in the vertical extent by the same elementary findings or the emergence of more severe findings in the same zones compared to the previous examination. Logistic regression analysis was used to assess the possible factors identified in univariate analysis.

Results: This study included 104 patients with 215 lung CT scans for analysis. Radiographic progression was seen in 43 patients (41.3%). Male sex, findings compatible with ILD on the last X-ray, age at diagnosis of ILD > 50 years, and presence of ground-glass opacity on CT were more common in the group with progression. In multivariate analysis (adjusted for ILD disease duration), findings consistent with ILD on chest X-ray and male sex were independent risk factors for progression, while taking methotrexate (ever) was an independent protective factor for progression.

Conclusion: Our findings indicate a negative association between methotrexate use and ILD progression. These results should be confirmed in further studies.

Objective: Osteoarthritis (OA) is a degenerative disease of the joints characterized by inflammation and cartilage degeneration. Zinc finger E-box binding homeobox 2 (ZEB2) contains various function domains that interact with multiple transcription factors involved in various cellular functions. However, the function of ZEB2 in OA has not been clearly illustrated.

Method: Interleukin-1β (IL-1β) was used to establish an OA model in vitro. We quantified the ZEB2 expression in cartilage tissues from OA patients and IL-1β-induced chondrocytes through reverse transcription-quantitative polymerase chain reaction and Western blot. We then used functional assays to explore the function of ZEB2 during OA progression.

Results: ZEB2 expression was increased in OA cartilage tissues and chondrocytes. The silencing of ZEB2 increased aggrecan and collagen II levels, and reduced the content of matrix metalloproteinase-3 (MMP-3), MMP-9, and MMP-13. ZEB2 knockdown inhibited the effects of IL-1β on the production of nitric oxide and prostaglandin E₂, and the expression of inducible nitric oxide synthase and cyclooxygenase-2. ZEB2 inhibition also suppressed the levels of IL-6 and tumour necrosis factor-α, and increased the IL-10 level in IL-1β-treated cells. Mechanically, ZEB2 knockdown blocked the activation of the Wnt/β-catenin pathway in chondrocytes.

Conclusion: Knockdown of ZEB2 alleviated IL-1β-induced cartilage degradation and the inflammatory response through the Wnt/β-catenin pathway in chondrocytes.

Objective: To study the impact of tumour necrosis factor-α inhibitor (TNFi) therapy on the use of non-steroidal anti inflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) in Iceland.

Method: This registry cohort study used data from the nationwide database on biologics in Iceland (ICEBIO) and the Icelandic Prescription Medicines Register on disease activity, and filled prescriptions for NSAIDs, to study the period from 2 years before to 2 years after initiation of a first TNFi. Five randomly selected individuals from the general population matched on age, sex, and calendar time for each patient served as comparators.

Results: Data from 940 patients and 4700 comparators were included. Patients with arthritis were prescribed 6.7 times more defined daily doses of NSAIDs than comparators (149 vs 22 per year). After TNFi initiation, NSAID use decreased to a mean of 85 DDD per year, or by 42% in RA, 43% in PsA, and 48% in axSpA. At TNFi initiation, the quintile of axSpA patients who used most NSAIDs reported significantly worse pain (mean ± sd 66 ± 21 vs 60 ± 23 mm), global health (70 ± 20 vs 64 ± 23 mm), and Health Assessment Questionnaire score (1.21 ± 0.66 vs 1.02 ± 0.66) than the other patients, whereas no significant differences were observed in the groups with peripheral arthritis.

Conclusion: Patients with inflammatory arthritides requiring TNFi therapy use more NSAIDs than matched comparators, and consumption decreased following TNF initiation. Patient-reported measures are not associated with high NSAID use in patients with peripheral arthritis.