High serum levels of pro-matrix metalloproteinase-3 are associated with greater radiographic damage and the presence of the shared epitope in patients with rheumatoid arthritis

OBJECTIVE: To determine if there is a relationship between serum pro-matrix metalloproteinase-3 (proMMP-3) levels and radiographic damage in rheumatoid arthritis (RA), and to investigate whether high levels are associated with presence of the HLA-DRB1 shared epitope (SE). METHODS: Serum proMMP-3 levels were measured by ELISA on 45 RA patients with early disease and 292 with established disease. Early RA was arbitrarily defined as disease duration <3 years. Clinical and laboratory measures of disease activity and severity were obtained. Radiographic damage was assessed by scoring radiographs of the hands and feet using the method of Larsen. HLA-DRB1 typing was performed by sequence-specific oligonucleotide probing. Data were analyzed by multiple regression analysis. RESULTS: In all patients, there was a correlation (r = 0.318, p<0.0001) between serum proMMP-3 levels and Larsen scores. Other correlations were found with Health Assessment Questionnaire score (r = 0.261, p<0.0001) and C-reactive protein (CRP) (r = 0.357, p<0.0001) levels. ProMMP-3 levels were significantly higher in SE+/+ patients than in those completely lacking the SE, with the highest levels in patients carrying an HLA-DRI+/DR4+ phenotype. The greatest difference in proMMP-3 levels between SE+/+ and SE-/- patients was in those with a disease duration <3 years (381.6 vs. 71.7 ng/ml; p = 0.02). CONCLUSION: Our data indicate that there is a significant relationship between radiographic damage and serum levels of proMMP-3. As well, higher circulating levels of proMMP-3 are found in patients positive for the SE, particularly in early RA, and this may partly explain the association between the SE and more erosive disease.     

Serum and synovial fluid interleukin-17 concentrations in rheumatoid arthritis patients: Relation to disease activity,radiographic severity and power Doppler ultrasound

Aim of the workTo investigate serum and synovial fluid levels of IL-17 in rheumatoid arthritis (RA) patients, and its correlation with disease activity and severity.Patients and methods20 RA patients together with 20 primary knee osteoarthritis (KOA) patients and 15 healthy individuals matched for age and sex as control groups were enrolled in this study. Both RA and KOA patients presented with knee effusion. Paired samples of serum and synovial fluid (SF) were collected from RA, OA patients and serum samples from the healthy individuals. RA disease activity was assessed using DAS-28 score and power Doppler ultrasound (PDUS) according to the European League against Rheumatism (EULAR). Radiographic damage was evaluated according to Larsen score.ResultsSerum levels of IL-17 were significantly elevated in RA patients compared to controls (p < 0.001). Also, SF of IL-17 was significantly higher in RA patients compared to OA patients (p < 0.001). In addition, synovial level of IL-17 was significantly higher in RA patient compared to their serum level (p < 0.001). Regarding disease activity grading among RA patients, significant differences (p < 0.05) in mean serum and synovial IL-17 levels were reported being higher in severe active disease. Positive correlations of serum and SF IL 17 levels with PDUS findings and Larsen score were reported.ConclusionSerum and synovial IL-17 levels were significantly elevated in RA patients which clarifies its possible role in RA pathogenesis and correlates positively with disease activity parameters, PDUS findings and Larsen score. Thus targeting IL-17 may provide a promising role in suppressing RA.     

The levels of serum-soluble Fas in patients with rheumatoid arthritis and systemic sclerosis

Different defects in Fas/APO-1 interaction with its ligand or in signaling of apoptosis may contribute to autoimmune disease. The aim of this study was to examine whether elevated serum-soluble Fas (sFas) levels are associated with rheumatoid arthritis (RA) or systemic sclerosis (SSc). sFas level was assayed using a sandwich ELISA in serum from 37 patients with RA, 30 patients with SSc and 20 healthy controls. The RA patients were classified according to disease activity, anatomical joint damage, and the presence of pulmonary involvement. Presence of pulmonary fibrosis, CO diffusion capacity (DLCO) and skin score were determined in patients with SSc. Serum sFas levels were not significantly different between study groups. Serum sFas level in the active RA patients was significantly higher than in the patients with inactive disease (p<0.05). The untreated active RA patients had significantly higher sFas level than healthy controls (p<0.05). In RA patients, sFas level was significantly correlated with rheumatoid factor titer (p=0.01), C-reactive protein (p<0.05), and erythrocyte sedimentation rate (p<0.05). The RA patients with severe joint damage had significantly higher sFas level than those with mild joint damage (p<0.05). The untreated SSc patients had significantly higher sFas levels than the treated SSc patients and healthy controls (p<0.01). Serum sFas level was not correlated with presence of pulmonary fibrosis, DLCO or skin score. The soluble Fas molecule may provide a useful additional marker for assessment of disease activity and severity in patients with RA.Abbreviations CRP C-reactive protein - DLCO CO diffusion capacity - ESR Erythrocyte sedimentation rate - RA Rheumatoid arthritis - RF Rheumatoid factor - sFas Serum-soluble Fas - SSc Systemic sclerosis     

血清骨桥蛋白水平与类风湿关节炎活动性的关系及在伴肺间质病变中的意义

目的 检测类风湿关节炎(RA)患者血清骨桥蛋白(OPN)水平,分析血清OPN水平与RA疾病活动的相关性,初步探讨OPN在RA合并肺间质病变(ILD)发病机制中的作用.方法 收集临床确诊的65例RA患者血清.其中活动期RA患者43例,缓解期RA患者22例;其中合并ILD者24例,未合并ILD者41例.以20名健康体检者血清为健康对照组.采用酶联免疫吸附法(ELISA)检测血清OPN水平,并与RA患者的临床及实验室指标进行相关性分析.结果 ①RA组血清OPN水平(中位数18.0 ng/ml),高于健康对照组(中位数14.0 ng/ml,P<0.01);活动期RA组血清OPN水平(中位数20.0 ng/ml),高于缓解期RA组(中位数1.5 ng/ml,P<0.01).②RA组血清OPN水平与病程、关节压痛数、红细胞沉降率(ESR)、C反应蛋白(CRP)等呈显著正相关,与关节肿胀数无相关性.③RA合并ILD组血清OPN水平(中位数20.0 ng/ml),高于RA未合并ILD组(中位数17.0 ng/ml,P<0.05);且与动脉氧分压(PaO2)呈负相关;与肺功能(肺活量、一氧化碳弥散吸收率)无相关性.④RA合并ILD组关节压痛数,关节肿胀数、ESR、CRP等与RA未合并ILD组相比差异具有统计学意义(P均<0.01);RA合并ILD组血清类风湿因子(RF)(IgM)高于RA未合并ILD组(P<0.05).结论 OPN在RA发病机制中具有一定意义且与RA活动性有关,可作为评价疾病活动度的炎性指标;OPN参与了RA合并ILD的发生及进展,并与肺损害严重程度有关.     

Serum sclerostin levels in rheumatoid arthritis

BackgroundRheumatoid arthritis (RA) is an autoimmune disease that may lead to joint destruction and disability. Wingless (Wnt) pathway is involved in bone formation and has been found to contribute to bone loss in RA. Sclerostin is a key molecule in Wnt pathway.ObjectiveTo study the serum levels of sclerostin in rheumatoid arthritis patients and to study its association with radiological changes.MethodsForty-five patients with RA and 45 age and gender matched healthy controls were enrolled. Serum sclerostin was measured by ELISA. Modified version of Larsen score was used to assess joint damage in radiographs and Magnetic resonance imaging (MRI) of wrist and hand was assessed for synovitis and bone erosion.ResultsSerum sclerostin levels were higher in patients with RA as compared to controls (p < 0.01). Serum sclerostin levels correlated with ESR (r = 0.655), CRP(r = 0.623), modified DAS 28 (r = 0.711), MRI synovitis (r = 0.802) and MRI erosion score (r = 0.832).ConclusionIncreased serum levels of sclerostin may play a role in joint damage and bone erosion in RA.     

Serum matrix metalloproteinase 3 as a predictor of the degree of joint destruction during the six months after measurement, in patients with early rheumatoid arthritis

OBJECTIVE: To evaluate whether matrix metalloproteinase 3 (MMP-3), a proteinase that is expressed in rheumatoid synovial tissue and shows potent activity in degrading the proteoglycan of cartilage, plays a pivotal role in the joint destruction seen in early rheumatoid arthritis (RA). METHODS: In a prospective study of patients with early RA, the relationship between the serum concentration of MMP-3, as determined by a sandwich enzyme immunoassay system, and the progression of joint destruction in patients with early RA, as measured by the Larsen radiologic score, was investigated. RESULTS: Serum MMP-3 levels were elevated in the RA patients compared with healthy controls, not only in the late stage, but also in the early stage of the disease in patients whose duration of RA was <4 months. The serum MMP-3 level at entry into the study had a strong correlation with the Larsen score at 6 months and 12 months after entry (r = 0.58 and r = 0.49, respectively). Similarly, the serum MMP-3 level at 12 months and 24 months after entry showed a positive association with the Larsen score in the subsequent 6-12 months. Suppression of the serum MMP-3 level in the first year led to a decline in joint damage in the second year. CONCLUSION: The serum concentration of MMP-3 is a useful marker for predicting bone damage in the early stage of RA, and the suppression of MMP-3 production may be an effective therapeutic approach for patients with early RA.     

Cytokines, metalloproteinases, their inhibitors and cartilage oligomeric matrix protein: relationship to radiological progression and inflammation in early rheumatoid arthritis. A prospective 5-year study

OBJECTIVE: To assess how serum concentrations of some cytokines, proteases and their inhibitors and cartilage oligomeric matrix protein (COMP) relate to the evolution of clinical disease and joint damage in early rheumatoid arthritis (RA). METHODS: Annual assessment was performed in 24 RA patients subdivided into three groups according to disease severity as determined by the radiological progression rate. All patients were followed for 5 yr after inclusion. Functional status, Larsen's radiographic index in hands and feet (joint damage score, JDS) and C-reactive protein (CRP) were assessed annually and compared with interleukin (IL)-6, IL-10, the IL-1 receptor antagonist (IL-1Ra), promatrix metalloproteinase 3 (proMMP-3), tissue inhibitor of metalloproteinases 1 (TIMP-1) and COMP, which were determined by specific immunological tests. RESULTS: The median JDS was initially between 4.5 and 7. During the study time the progression of JDS was 1 (median) for patients with slow progression, 33 for patients with intermediate progression and 62 for patients with rapid progression. Changes in CRP and proMMP-3 concentrations over time differed significantly between the groups, but no significant difference was observed for IL-1Ra, TIMP-1 or COMP. ProMMP-3 was closely related to CRP at each time point. IL-6 correlated significantly with CRP at the last four annual follow-up examinations. CRP and proMMP-3 correlated with JDS at the last two or three examinations and the combined levels of these markers over 5 yr correlated significantly with joint damage progression (Spearman rank correlation 0.73 and 0.74 respectively). IL-1Ra showed a weak negative correlation with JDS, and COMP tended to correlate with JDS only at the start. The initial proMMP-3 concentration was the only significant variable predicting rapidly developing joint damage, but the predictive value was low. CONCLUSIONS: ProMMP-3 correlated closely at all time points with CRP, but gave little or no additional clinical information regarding inflammation or radiographic progression. IL-1Ra and TIMP-1 showed weaker, acute-phase-like variation, which may reflect pathogenic agonist/inhibitor imbalance in the evolution of RA. COMP, in contrast, did not reflect the inflammatory CRP-related component of the disease or the destructive aspect in this study.     

Serum matrix metalloproteinase 3 levels in comparison to C-reactive protein in periods with and without progression of radiological damage in patients with early rheumatoid arthritis

OBJECTIVE: To evaluate serum matrix metalloproteinase 3 (MMP-3) levels in comparison to C-reactive protein (CRP) in periods with and without progression of radiological damage in patients with early rheumatoid arthritis (RA). METHODS: Thirty-two patients with RA and radiological progression (> or = 5 points according to the Sharp/van der Heijde method) during 6 months followed by a 6-month period without radiological progression (< or = 1 point) were selected from a prospective follow-up study of early RA patients. Serum MMP-3 levels, CRP, the erythrocyte sedimentation rate (ESR), disease activity index (DAS), swollen joint count (SJC), tender joint count (TJC), and Ritchie articular index (RAI) were measured monthly and results were transformed into mean values for the 6-month periods. RESULTS: During the period with radiological progression the mean serum MMP-3 correlated significantly with the mean CRP (r = 0.68, p < 0.001), ESR (r = 0.54, p = 0.001) and swollen joint count (r = 0.48, p = 0.006). In the period without radiological progression the mean serum MMP-3 only correlated with the mean CRP (r = 0.44, p = 0.012). Individual changes--expressed in percentages (%)--between the two periods showed a decrease in both the mean serum MMP-3 and CRP in 19 and an increase in 3 patients, in parallel with other markers of disease activity in these patients (69% of cases). The individual change (%) in mean serum MMP-3 or CRP did not correlate with the difference in radiological progression between the two periods. CONCLUSIONS: Serum MMP-3 and CRP are closely related and there seems to be no difference between serum MMP-3 and CRP with regard to the monitoring of the progression of radiological damage.     

The relationship of serum calprotectin with disease activity,functional status,ultrasonographic findings and radiological damage in rheumatoid arthritis patients

Aim of the workTo measure the levels of serum calprotectin (CLP) in rheumatoid arthritis (RA) patients and to assess its association with disease activity, functional status, ultrasonographic findings, and radiological damage.Patients and methodsThis study included 47 RA patients and 33 controls. The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (anti-CCP), rheumatoid factor (RF), C-reactive protein (CRP), disease activity score (DAS28), health assessment questionnaire (HAQ), modified Larsen radiological score, musculoskeletal ultrasound and serum CLP levels were assessed.ResultsThe mean age of the patients was 42.5 ± 12.8 years; 34 females and 13 males (F:M 2.6:1) with a mean disease duration of 2.6 ± 1.1 years. RF was positive in 72%. CLP level was significantly increased in patients compared to control (2.78 ± 0.89 μg/ml vs. 0.84 ± 0.5 μg/ml; p < 0.001) and in those with activity (3.27 ± 0.75 μg/ml) compared to those in remission (1.92 ± 0.15 μg/ml). A significant correlation was detected between CLP and DAS28, ESR, CRP, HAQ, and modified Larsen scores (p < 0.001). On regression, tender and swollen joint counts, ESR, CRP, HAQ, modified Larsen, ultrasound 7 score and CLP level were significant predictors of activity but were insignificant on multivariate analysis. At a cut-off value of 2.35 μg /ml CLP can significantly differentiate active RA patients from those in remission (AUC 0.95; p < 0.001) at a sensitivity of 90%, specificity of 100%, and accuracy of 95%.ConclusionThe serum CLP levels were significantly high in RA patients and these high levels were associated with disease activity, functional status, ultrasonographic findings, and radiological damage.     

Relationship between pentosidine levels in serum and urine and activity in rheumatoid arthritis

Pentosidine is one of the advanced glycation end-products and is formed by glycosylation and oxidation. The aim of this study is to investigate the relationship between serum and urinary pentosidine levels and the activity of rheumatoid arthritis (RA). Using HPLC with column switching, we measured pentosidine in serum and urine from 77 patients with RA and 62 normal control subjects. The clinical features, blood biochemistry and activity of inflammation were examined in RA patients. Serum and urinary pentosidine in RA were significantly higher than in controls. Pentosidine significantly correlated with age, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor, joint score and Lansbury Index in RA. The levels of pentosidine were higher in patients with active RA than in those with inactive RA. Serum and urine levels of pentosidine correlated with the activity of RA, and serum and urinary pentosidine may be a significant and novel marker for evaluating the disease status and the activity of RA.      

The relationship between serum levels of YKL-40 and disease progression in patients with early rheumatoid arthritis

YKL-40 concentrations in serum were determined by an ELISA at 3 occasions during 19 months for 57 early RA patients. The results were related to biochemical and radiographic measures at each time point. YKL-40 correlated significantly to ESR and CRP throughout the study. Correlations between YKL-40 and radiographic findings scored by the Larsen method were fairly weak both for absolute values at each time point (Rs 0.212-0.319) and for progression over time (Rs 0.152-0.301). Baseline YKL-40 could predict radiographic progression with a specificity and sensitivity of only slightly over 50%. ESR and CRP correlated stronger than YKL-40 to joint damage progression and in a multiple regression model ESR was the only significant variable explaining the variance of this radiographic measure. We conclude that serial measurements of serum YKL-40 did not provide information that could not be obtained by conventional biochemical measures of disease activity.     

类风湿关节炎患者血清肽酰基精氨酸脱亚氨酶4水平及其意义

目的 通过检测肽酰基精氨酸脱亚氨酶(PADI)4在类风湿关节炎(RA)患者血清中的水平,探讨其在RA发病机制中的意义.方法 采用ELISA检测100例RA患者、23例其他风湿病患者、24例健康体检者血清中PADI4及抗环瓜氨酸多肽(CCP)抗体水平.结果 (1)RA患者PADI4水平为(620.10±259.82)μg/L,较其他风湿病患者[(404.41±195.38)μg/L]、健康体检者[(522.19±142.40)μg/L]明显升高,差异有统计学意义(F=8.75,P＜0.001).(2)RA患者PADI4-94(rs 2240340)基因型T/T、C/C、T/C PADI4水平分别为(597.43±255.76)μg/L、(674.63±320.67)/μgL、(628.78±274.13)μg/L;PADI4-104(RS 1748033)基因型T/T、Cμg/C、T/C PADI4水平分别为(571.56±138.34)μg/L、(653.41±300.35)μg/L、(640.07±302.82)μg/L.各基因型间PADI4水平差异无统计学意义(P＞0.05).(3)相关性分析:RA组PADI4水平与RA疾病活动评分(DAS28)、ESR呈正相关(r=0.24,P=0.03;r=0.23,P=0.03),而与抗CCP抗体、抗PADI4抗体、C反应蛋白无相关性(r=0.02,P=0.83;r=-0.17,P=0.10;r=0.14,P=0.18).结论 PADI4可能是RA的一个致病性抗原,参与了RA发病,其水平高低反映病情活动程度.

Abstract：

Objective To detect the levels of serum peptidylarginine deiminase (PADI)4 and explore its significance in rheumatoid arthritis ( RA ). Methods The presence of PADI4, anti-PADI4antibodies and anti-cyclic citrullinated peptide (CCP) antibodies levels were examined by enzyme-linked immunosorbent assay (ELISA). Serum samples were obtained from 100 patients with RA, 23 patients with other rheumatic diseases, and 24 healthy controls. The associations between PADI4 and the disease activity score using 28 joint counts ( DAS28 ) score, anti-CCP antibodies, erythrocyte sedimentation rate ( ESR ),C-reactive protein ( CRP), PADI4-94 ( rs 2240340 ) and PADI-104 ( rs 1748033 ) gene polymorphisms and other indexes were analyzed in RA. Results The levels of PADI4 in RA patients were significantly higher than in other rheumatic diseases and healthy controls ( F = 8. 75, P ＜ 0. 001 ). There was no significantly difference in levels of PADI4 among ADI4-94 ( rs 2240340)/PADI-104 ( rs 1748033 ) genotypes. Conclusions PADI4 is associated with disease activity involved in the RA pathogenesis and may be a RA pathogenic antigen.     

Cartilage Oligomeric Matrix Protein (COMP): Die Rolle eines nichtkollagenen Knorpel-Matrix- Proteins als Marker der Krankheitsaktivität und Gelenkzerstörung bei Patienten mit rheumatoider Arthritis und Arthrose

Today, we can assess criteria to predict the tissue destruction and progression of Rheumatoid Arthritis (RA) and Osteoarthritis (OA) only in a late stage of the disease. It would be an advantage to have biochemical markers of disease activity and joint destruction to optimize therapy. PATIENTS AND METHODS: In this cross-sectional study with 37 RA and 20 OA patients (disease duration 119 +/- 130 months for RA and 41 +/- 73 months for OA), ESR, CRP, disease activity score (DAS), the functional status of RA (American College of Rheumatology), and the radiological scoring systems of Larsen and Kellgren/Lawrence, respectively, were used as parameters for disease activity and joint destruction. Cartilage oligomeric matrix protein (COMP) was measured with an enzyme-linked immunosorbent assay (ELISA) in serum and synovial fluid, COMP fragments with immunoblot in the synovial fluid. RESULTS: The mean COMP value in synovial fluid was 38 ug/ml (RA) and 46 ug/ml (OA); 6.5 ug/ml (RA) and 3.4 ug/ml (OA) in serum. RA patients had a higher amount of small COMP fragments in synovial fluid than OA patients. In RA patients, there was a significant positive correlation between disease activity (DAS) and COMP in synovial fluid and serum, a negative correlation between functional status of RA and serum COMP and between radiologic joint destruction of the knee and serum COMP. In OA patients, there was a significant correlation of joint space width and synovial fluid COMP. DISCUSSION: A high clinical disease activity (DAS) correlated with high COMP values in serum and synovial fluid and with increasing proteolytic activity (higher amount of small COMP fragments especially in RA). An increased turnover of cartilage matrix in joint inflammation might explain this correlation. The correlation of decreased COMP with decreased functional status in RA and increased joint destruction is compatible with a loss of cartilage and less turnover. The correlation between joint space width and increased COMP in OA patients with short disease duration might be explained with a higher turnover of the cartilage matrix in the early stage of the disease.     

Serum MMP-3 and MMP-1 and progression of joint damage in early rheumatoid arthritis

OBJECTIVE: Expression and activation of matrix metalloproteinases such as MMP-3 (stromelysin-1) and MMP-1 (collagenase-1) are increased in patients with rheumatoid arthritis (RA). Previous negative reports of their value as predictors of joint damage may be due to the lack of a large longitudinal study of early RA patients. This study evaluated their use in assessing early untreated patients with RA and predicting subsequent joint damage. METHODS: Ninety-eight patients with early untreated RA of less than 12 months duration and 20 normal controls had baseline serum samples tested with a double-antibody enzyme-linked immunosorbent assay for each of MMP-1 and MMP-3. The subsequent changes in Larsen score (DeltaLarsen) and Health Assessment Questionnaire (DeltaHAQ) over the first 12 months were recorded. RESULTS: Baseline serum levels of MMP-3 and MMP-1 correlated significantly with baseline C-reactive protein (CRP) (r=0.42 and 0.49, P<0.001), DeltaHAQ (r=0.32 and 0.30, P<0.01) and DeltaLarsen (r=0.23 and 0.32, P<0.05) respectively. Analysis of the group of patients with a normal CRP at presentation (n=21) showed correlation of the baseline MMP-3 and MMP-1 with the presence of erosive disease during the first 12 months (r=0.52 and 0.65 respectively, P<0.05). Logistic regression analysis, in the patients who were non-erosive at presentation, showed that the strongest correlation with progression in Larsen score was the baseline MMP-3 level (r=0.30, P=0.01). CONCLUSIONS: Baseline serum MMP-1 and MMP-3 levels correlate with disease activity and predict functional and radiographic outcome in early untreated RA. They may have a particular value in predicting the progression of erosive disease in patients who are not erosive at presentation.     

Serum vascular endothelial growth factor in late rheumatoid arthritis.

OBJECTIVES: To investigate the serum levels of VEGF in patients with rheumatoid arthritis of long duration. METHODS: Serum VEGF levels were measured in 118 patients with long-standing rheumatoid arthritis according to the ACR criteria (mean duration 12 years). The disease activity score was evaluated by the method of van der Heijde et al. RESULTS: Serum levels of VEGF in patients with RA were significantly higher than in healthy controls. VEGF levels showed no correlation with CRP, SAA amyloid protein, or the disease activity score. CONCLUSIONS: Our findings suggest that, contrary to the results reported in patients with early onset RA, where VEGF appears to play an active part in joint inflammation, in long-standing RA elevated VEGF serum levels may be an independent marker although its significance remain to be established.     

类风湿关节炎患者血清和关节液趋化因子RANTES的测定及其意义

目的：探讨血清、关节液中激活正常T细胞表达和分泌因子（RANTES）水平与类风湿关节炎（RA）病变活动的相关性。方法：有和酶联免疫吸附法（ELISA）测定28例类风湿关节炎患者血清及关节液中RANTES水平,并与骨关节炎（OA）患者对照,结果：RA患者血清RANTES水平明显高于OA,且RA滑液中RANTES水平高于血清,血清RANTES水平与关节肿胀指数,血沉,C反应蛋白呈正相关,结论：RA病变关节组织是RANTES产生的主要部位;血清RANTES水平与RA的活动性病变相关。     

Relation between body mass index and radiological progression in patients with rheumatoid arthritis

OBJECTIVE: To determine if there is an influence of body mass index (BMI) on the radiological progression in early and longer duration rheumatoid arthritis (RA). METHODS: Fifty-four patients with RA were observed in a progressive 2 year followup for radiological progression of joint damage. At the beginning of study, 27 (50%) patients had a duration of complaints less than 6 months, grouped as early RA. BMI at the beginning and end of the study were monitored, together with HLA-DRB1 alleles, initial joint erosions, duration of disease, age, sex, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Outcome was defined as radiographic damage according to yearly increase of Larsen score. RESULTS: Increased radiographic joint damage of patients was significantly correlated with lower BMI at the beginning of the study (r = 0.363, p < 0.05), the presence of initial joint erosions (r = 0.341, p < 0.01), ESR (r = 0.315, p < 0.05), and CRP at study entry (r = 0.427, p < 0.01). Patients with an increase of Larsen score > or = 5.8/year were found to have a lower weight at the beginning of their complaints (BMI 24.8 +/- 4.7 vs 27.8 +/- 3.8; p < 0.05) as well as after the time of observation (BMI 24.6 +/- 3.7 vs 27.6 +/- 4.9; p < 0.05). Stepwise logistic regression analysis revealed a BMI < 27 at the beginning of disease (beta = 2.04, p = 0.003, odds ratio = 7.69), the presence of HLA-DR4 shared epitope (beta = 1.76, p = 0.015, OR 5.82), and joint erosions at study entry (beta = 1.56, p = 0.044, OR 4.78) as significant predictors for rapid joint damage. CONCLUSION: Together with the presence of HLA-DR4 shared epitope and erosive disease at study entry, a low BMI at the beginning of RA was found in association with higher radiographic progression in RA. Accordingly, BMI could be of interest as a sensitive and inflammation-independent predictor for radiological outcome of RA.     

血清高迁移率族蛋白1水平与类风湿关节炎临床指标的相关性

目的通过检测活动性类风湿关节炎(rheumatoid arthritis,RA)患者血清高迁移率族蛋白1(high mobility group box protein 1,HMGB1)表达水平,探讨HMGB1与RA患者疾病活动性、自身抗体及临床指标的相关性。方法采用双抗体夹心酶联免疫吸附试验测定67例活动性RA患者和21位健康对照者血清HMGB1水平。收集RA患者的同期临床资料并测定相关实验室指标:疼痛视觉模拟评分(visual analog scale,VAS)、疲乏VAS、肿胀关节数、压痛关节数、患者对疾病总体状况的VAS(patient′s global assessment,PGA)、健康评估问卷(health assessment questionnaire,HAQ)、疾病活动评分28(dise aseactivity score28,DAS28)、血沉、C-反应蛋白、类风湿因子-IgM、抗环瓜氨酸肽抗体等,分析以上指标与血清HMGB1的相关性。结果活动性RA组血清HMGB1中位数为8.7ng/ml,四分位间距为16.59ng/ml;健康对照组血清HMGB1中位数为3.47ng/ml,四分位间距为7.43ng/ml,活动性RA组血清HMGB1表达水平显著高于健康对照组,两组间比较差异有统计学意义(P0.01)。活动性RA患者血清HMGB1表达水平与类风湿因子呈正相关(P0.01),与疼痛VAS评分、疲乏VAS评分、肿胀关节数、压痛关节数、PGA、HAQ、DAS28评分及血沉、C-反应蛋白、抗环瓜氨酸肽抗体无相关性(P0.05)。结论活动性RA患者血清HMGB1表达水平较健康对照组显著升高,但可能与疾病活动无关。     

Value of serum and synovial fluid activin A and inhibin A in some rheumatic diseases

Aim: The purpose of the study is to measure serum and synovial fluid levels of activin A and inhibin A in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and osteoarthritis (OA) and correlate them with disease activity parameters. Subjects and methods: This study included 60 patients with various rheumatic diseases (20 with RA, 20 with SLE and 20 with OA), as well as 10 healthy controls. All of them were subjected to complete history‐taking, examination and estimation of disease activity index. The following investigations were done for all subjects: serum and synovial activin A, inhibin A, erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), anti‐dsDNA and complements 3 and 4. Results: Serum levels of activin A were significantly higher in RA, SLE and OA than controls and in RA and SLE versus OA The mean values of serum inhibin A were significantly higher in all studied groups than controls. Synovial activin A and inhibin A were significantly higher in RA than OA. Positive correlations were found between serum activin A and disease activity parameters of RA. In SLE, positive correlations were found between serum activin A and inhibin A with ESR and SLE Disease Activity Index. Conclusions: Serum activin A and inhibin A were significantly higher in RA and SLE. Serum levels correlated positively with disease activity parameters of RA and SLE. However, synovial levels were significantly higher in RA than OA but showed no correlation or negative correlation with disease activity. We recommend further studies to detect the exact role of activin A and inhibin A in these conditions.     

A comparative evaluation of quality of life and life satisfaction in patients with psoriatic and rheumatoid arthritis

Both rheumatoid arthritis (RA) and psoriatic arthritis (PsA) have a negative impact on patients’ quality of life (QOL). The aim of this study was to compare QOL and life satisfaction in patients with RA and PsA. Forty patients with PsA, 40 patients with RA, and 40 healthy control subjects were included in the study. Demographic data and clinical characteristics including age, sex, disease duration, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), peripheral pain assessed by visual analog scale (VAS) and Larsen scores of hand X-rays were recorded. Nottingham Health Profile (NHP) was used to evaluate QOL, and Life satisfaction index (LSI) was used to measure psychological well-being in both groups. The demographic data of the subjects were similar between the groups. The scores of all NHP subscales were significantly higher and the scores of LSI were significantly lower in PsA and RA patients than in control subjects. The inflammation markers including ESR, CRP, pain by VAS and Larsen scores were found to be significantly higher in RA patients. The scores of LSI were similar between the groups. Although the scores of physical domains of NHP (pain and physical disability) were statistically higher in RA patients (p<0.05), the scores of psychosocial subgroups of NHP were similar between RA and PsA patients (p>0.05). Both PsA and RA patients had disturbed QoL and decreased life satisfaction. In conclusion, peripheral joint damage, inflammation, and physical disability are significantly greater in RA but psychosocial reflection of QOL and life satisfaction are the same for both groups which can be explained by the additional impact of skin disease in patients with PsA.