Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1

Hormone replacement therapy (HRT) modulates the imbalance in bone remodeling, thereby decreasing bone loss. Sex hormones are known to influence rheumatic diseases. The aim of this study was to investigate the effects of HRT on the serum levels of hormones and cytokines regulating bone turnover in 88 postmenopausal women with active rheumatoid arthritis (RA) randomly allocated to receive HRT plus calcium and vitamin D(3 )or calcium and vitamin D(3 )alone for 2 years. An increase in estradiol (E(2)) correlated strongly with improvement of bone mineral density in the hip (P < 0.001) and lumbar spine (P < 0.001). Both baseline levels and changes during the study of IL-6 and erythrocyte sedimentation rate were correlated positively (P < 0.001). HRT for 2 years resulted in an increase of the bone anabolic factor, insulin-like growth factor 1 (IGF-1) (P < 0.05) and a decrease of serum levels of soluble IL-6 receptor (sIL-6R) (P < 0.05), which is known to enhance the biological activity of IL-6, an osteoclast-stimulating and proinflammatory cytokine. Baseline levels of IL-6 and IGF-1 were inversely associated (P < 0.05), and elevation of IGF-1 was connected with decrease in erythrocyte sedimentation rate (P < 0.05) after 2 years. Interestingly, increase in serum levels of E(2 )was associated with reduction of sIL-6R (P < 0.05) and reduction of sIL-6R was correlated with improved bone mineral density in the lumbar spine (P < 0.05). The latter association was however not significant after adjusting for the effect of E(2 )(P = 0.075). The influences of IGF-1 and the IL-6/sIL-6R pathways suggest possible mechanisms whereby HRT may exert beneficial effects in RA. However, to confirm this hypothesis future and larger studies are needed

Bone mineral density by digital X-ray radiogrammetry is strongly decreased and associated with joint destruction in long-standing Rheumatoid Arthritis: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The aims were to explore bone mineral density (BMD) by digital X-ray radiogrammetry (DXR) in postmenopausal women with long-lasting rheumatoid arthritis (RA) in relation to dual x-ray absorptiometry (DXA)-BMD, joint destruction by conventional radiographs and disease related variables in a cross-sectional study.</p> <p>Methods</p> <p>Seventy-five postmenopausal women with RA were examined by DXA measuring DXA-BMD of the forearm, total hip and lumbar spine, by scoring joint destruction on plain radiographs by the method of Larsen and by DXR-BMD in metacarpals two to four. The DXR-BMD results of the RA women were compared with an age and sex-matched reference database. A function of DXR-BMD in relation to age and disease duration was created. Associations were investigated by bivariate and multiple linear regression analyses.</p> <p>Results</p> <p>DXR-BMD was strongly decreased in RA patients compared to the reference database (p < 0.001). Calculations showed that DXR-BMD was not markedly influenced the first years after diagnosis of RA, but between approximately 5-10 years of disease there was a steep decline in DXR-BMD which subsequently levelled off. In multiple regression analyses disease duration, CRP and DXR-BMD were independent variables associated with Larsen score (R²= 0.64). Larsen score and BMD forearm were independent determinants of DXR-BMD (R²= 0.79).</p> <p>Conclusions</p> <p>DXR-BMD was strongly reduced and associated with both Larsen score and DXA-BMD forearm in these postmenopausal women with RA implying that DXR-BMD is a technique that reflects both the erosive process and bone loss adjacent to affected joints.</p

Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases

Objective Copy number variation of the C4 complement components, C4A and C4B, has been associated with systemic inflammatory autoimmune diseases. This study was undertaken to investigate whether C4 copy number variation is connected to the autoimmune repertoire in systemic lupus erythematosus (SLE), primary Sjögren's syndrome (SS), or myositis. Methods Using targeted DNA sequencing, we determined the copy number and genetic variants of C4 in 2,290 well-characterized Scandinavian patients with SLE, primary SS, or myositis and 1,251 healthy controls. Results A prominent relationship was observed between C4A copy number and the presence of SSA/SSB autoantibodies, which was shared between the 3 diseases. The strongest association was detected in patients with autoantibodies against both SSA and SSB and 0 C4A copies when compared to healthy controls (odds ratio [OR] 18.0 [95% confidence interval (95% CI) 10.2–33.3]), whereas a weaker association was seen in patients without SSA/SSB autoantibodies (OR 3.1 [95% CI 1.7–5.5]). The copy number of C4 correlated positively with C4 plasma levels. Further, a common loss-of-function variant in C4A leading to reduced plasma C4 was more prevalent in SLE patients with a low copy number of C4A. Functionally, we showed that absence of C4A reduced the individuals’ capacity to deposit C4b on immune complexes. Conclusion We show that a low C4A copy number is more strongly associated with the autoantibody repertoire than with the clinically defined disease entities. These findings may have implications for understanding the etiopathogenetic mechanisms of systemic inflammatory autoimmune diseases and for patient stratification when taking the genetic profile into account.publishedVersio

Decreased levels of T follicular helper (CD4+CXCR5+) cells and CD27+CD38+ and CD27+CD38− B cells in ankylosing spondylitis patients correlate with markers of inflammation

The purpose of this study was to study CD4+CXCR5+ T follicular helper (TFH) cells, CD27+CD38+ plasmablasts and CD27+CD38− memory B cells, as well as disease-related factors in patients with ankylosing spondylitis (AS) from northern Sweden. Peripheral blood mononuclear cells (PBMC) from 50 patients with AS (mean age 52 ± 9 years, 66% men, 100% HLA-B27 positive) and 50 pairwise matched blood donor controls (mean age 54 ± 9 years, 66% men) were stained with antibodies for CD27, CD38, CD19, CD3, CD4 and CXCR5 markers and analysed by flow cytometry. Patients with AS were examined with spinal x-ray for radiographic alterations (mSASSS), and plasma levels of C-reactive protein, erythrocyte sedimentation rate, as well as selected proinflammatory and regulatory cytokines were determined. Physical mobility, function and disease activity were registered by BASMI, BASFI and ASDAS-CRP, BASDAI, respectively. Comparing AS patients and controls pairwise, we observed a 56% reduction of TFH cells in PBMCs from AS patients (P =.000008). Furthermore, a 20%-30% reduction in plasmablasts and B memory cells (P ≤.002 and P ≤.007, respectively) was observed. In female patients, negative correlations between ESR and TFH, plasmablasts and B memory cells were observed; Rs = −0.551, P ≤.02; Rs = −0.476, P ≤.05 and Rs = −0.522, P ≤.03, respectively. In addition, positive correlations between the regulatory cytokine IL-10 and the proportion of B cells, IL-22, and the proportion of plasmablasts as well as a negative correlation between levels of the proinflammatory cytokine IL-6 and TFH were detected. Our observations indicate a role of an aberrant humoral immune response related to inflammation in AS

Drug adherence, response and predictors thereof for tocilizumab in patients with rheumatoid arthritis: results from the Swedish biologics register.

To evaluate drug adherence, clinical response and predictors thereof for tocilizumab in patients with RA in routine care based on prospectively collected data from the Swedish biologics register, Anti-Rheumatic Therapies in Sweden

Patterns of comorbidity and disease characteristics among patients with ankylosing spondylitis : a cross-sectional study

The knowledge of the development of comorbidities in patients with ankylosing spondylitis (AS) is limited. The aim of this study was to analyse associations between AS disease characteristics and comorbidity and to evaluate patterns of comorbidities in patients with AS. Patients with AS, fulfilling the modified New York Criteria, were identified (n =3D 346, mean age 56 +/- 15 years, 75% men, 99% HLA B27 positive). Through a review of the patient records, data on disease activity parameters, laboratory results, disease manifestations, and diagnoses of any clinically significant comorbidity was obtained. Four categories of comorbidities of interest were identified: A. arrhythmias, conduction disorders, and valvular heart disease; B. atherosclerosis and atherosclerotic CVD; C. spinal and non-spinal fractures; and D. obstructive sleep apnoea syndrome. Associations between AS disease characteristics and comorbidities in categories were assessed in logistic regression models. Differences in proportions of comorbidities was analysed using two-sided chi-square. Age was associated with all four categories of comorbidities, and male sex with arrhythmias, conduction disorders, valvular heart disease, and obstructive sleep apnoea syndrome. Early disease onset and long disease duration, respectively, were associated with arrhythmias, conduction disorders, and valvular heart disease. Obstructive sleep apnoea syndrome was associated with features of the metabolic syndrome. Patients with atherosclerotic cardiovascular disease had an increased risk of most other comorbidities, similar to, but more pronounced than patients with arrhythmias, conduction disorders and valvular heart disease. Comorbid conditions motivate clinical awareness among patients with AS. Longitudinal studies are needed to establish preventive measures

Seasonal variations in fatigue in persons with rheumatoid arthritis : a longitudinal study

Background: Fatigue is a prominent symptom in persons with rheumatoid arthritis (RA). Although this symptom has been described to vary in duration and frequency little is known about fluctuations in fatigue over time and season. The aim of this study was to describe monthly and seasonal variations in fatigue, in persons with RA of working age. Methods: Sixty-five participants diagnosed with RA and aged 20-65 years were recruited from a rheumatology clinic in Sweden. The participants provided self-assessments of their fatigue at seven time points during the four seasons using a 0-100 mm visual analogue scale (VAS) and the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ). Multiple regression analysis using mixed models was used to analyze changes in fatigue over time. Results: The mean +/- SD of fatigue rated on the VAS was 51 +/- 13, indicating substantial fatigue. Analysis of monthly variation showed statistically significant variation in fatigue ratings concerning VAS fatigue score (p &lt; 0.01) as well as the BRAF-MDQ total score and Living, Cognition (p &lt; 0.001), and Physical (p &lt; 0.05) sub-scores, but not the BRAF-MDQ Emotional sub-score. The greatest variations were seen from January to September, with higher fatigue ratings in January. The changes in VAS fatigue scores over time were considered to be of clinical importance. Analysis of seasonal variation revealed a statistically significant seasonal variation in fatigue levels, with higher fatigue values during the winter as measured by VAS fatigue score (p &lt; 0.01) as well as BRAF-MDQ total score (p &lt; 0.01) and Physical and Living sub-scores (both p &lt; 0.01). The greatest variation was seen between winter and autumn for VAS fatigue and between winter and summer for BRAF-MDQ total score and Physical and Living sub-scores. There were no statistical differences in fatigue levels, monthly or seasonal, between sexes or age groups. Conclusions: The majority of rating scales used in this study showed fluctuations in fatigue, general and physical fatigue being significantly greater during the winter. As fatigue is a substantial symptom in many persons with RA, this information is important for rheumatology professionals when dealing with persons with RA in routine care