Serum matrix metalloproteinase 3 in early rheumatoid arthritis is correlated with disease activity and radiological progression

OBJECTIVE: To analyze the clinical significance of serial measurements of serum matrix metalloproteinase 3 (MMP-3) levels in relation to markers of disease activity and radiological progression in early rheumatoid arthritis (RA). METHODS: In a 3 year prospective study of 33 patients with early RA (symptoms < 1 year at entry) monthly measurements of serum MMP-3 were transformed into time integrated values for 6 month periods for comparison with other markers of disease activity like swollen joint count (SJC), tender joint count (TJC), Ritchie articular index (RAI), the disease activity score (DAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and radiological progression, scored according to Sharp's method, in which erosions and joint space narrowing are scored separately and combined to a total Sharp score. RESULTS: Significant correlations were found between serum MMP-3 and SJC, ESR, and CRP during all periods and between 6 and 30 months with the DAS. There were no correlations between serum MMP-3 and TJC or the RAI. During the first 12 months serum MMP-3 was correlated only with the item joint space narrowing of the Sharp score. After 12 months of followup it was also correlated with the total Sharp score and after 18 months it was correlated with all 3 items of the Sharp score. There was a wide interindividual variation in the relation between serum MMP-3 and radiological progression but intraindividually this relation seemed to be rather constant. CONCLUSION: Time integrated values of serum MMP-3 are correlated with time integrated values of other markers of disease activity such as joint swelling, ESR, CRP, and the DAS. Of the radiological scores, as outcome measures, especially joint space narrowing correlated closely with cumulative serum MMP-3.     

Serum levels of matrix metalloproteinase-3 in relation to the development of radiological damage in patients with early rheumatoid arthritis.

OBJECTIVE: To evaluate the significance of serum matrix metalloproteinase-3 (MMP-3) levels in relation to the development of radiological damage (X-ray damage) in early rheumatoid arthritis (RA). METHODS: Serum MMP-3 levels were measured in 46 healthy controls (CTRL), 19 osteoarthritis (OA) and 78 RA patients with joint symptoms for <1 yr at presentation (T0): 48 patients without and 30 with X-ray damage at T0. Serum MMP-3, measured by ELISA, and X-ray damage, scored according to Sharp's method, were assessed at 0, 6, 12 and 24 months. RESULTS: MMP-3 levels in CTRL and OA were low or undetectable with no differences between the groups (P=0.19). Levels in RA were higher than in CTRL (P<0.01). Initial MMP-3 levels in patients with X-ray damage at T0 (n=30) were higher than the levels in patients without any X-ray damage during follow-up (n=19) (P<0.01), but were not different from those in patients who developed X-ray damage during the study (n=29) (P=0.11). In the patients without X-ray damage at T0, there was a significant correlation between MMP-3 at T0 and the total X-ray damage after 6 months (r=0.34, P=0.02) and 12 months (r=0.32, P=0.03). This correlation was almost exclusively determined by joint space narrowing in the Sharp score. CONCLUSION: The serum MMP-3 level seems to be an indicator for the development of radiological damage in patients with early RA and appears to be particularly indicative of cartilage degradation.     

Serum matrix metalloproteinase 3 levels during treatment with sulfasalazine or combination of methotrexate and sulfasalazine in patients with early rheumatoid arthritis

OBJECTIVE: To determine the effects of treatment with sulfasalazine (SSZ) or the combination of methotrexate (MTX) and SSZ on serum matrix metalloproteinase 3 (MMP-3) levels in patients with early rheumatoid arthritis (RA). METHODS: Eighty-two patients with early RA (symptoms < 1 year and DMARD-naive at presentation) were selected who had been treated with SSZ (2000 mg/day) or with the combination of MTX (7.5-15 mg/week) and SSZ. Serum MMP-3 levels, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), swollen joint count (SJC), tender joint count (TJC), Ritchie articular index (RAI), and the Disease Activity Score (DAS) were determined at 4 week intervals during a followup of 28 weeks for each treatment group. Response was based on clinical grounds and CRP at 12, 20, and 28 weeks. RESULTS: SSZ responders (n = 52) had lower baseline values of serum MMP-3, CRP, and ESR, compared to partial/nonresponders (n = 30), but did not differ in joint scores and DAS. In the SSZ responder group all variables decreased. In the SSZ partial/nonresponders, CRP, ESR, and SJC decreased in contrast to serum MMP-3, TJC. RAI, and DAS-3. After addition of MTX all variables decreased in 24 of the 30 patients who had shown a partial or no response taking SSZ. In the SSZ responders there was a delayed decrease in serum MMP-3 compared to CRP. CONCLUSION: Serum MMP-3 levels decrease in patients with early RA who respond to SSZ or to the combination of MTX and SSZ. In patients who respond to SSZ the changes in serum MMP-3 levels indicate a delayed response compared to CRP.     

Serum soluble interleukin 2 receptor levels and radiological progression in early rheumatoid arthritis.

OBJECTIVE: To investigate the association between serum soluble interleukin 2 receptor (sIL-2R) levels and radiological changes in patients with early rheumatoid arthritis (RA). METHODS: sIL-2R levels from 155 patients with active RA were measured by immunoassay over a 2 year period and the associations with radiological change and other measures of disease activity were analyzed. RESULTS: The area under the curve for sIL-2R is weakly associated with the change in the modified Larsen score over a 2 year period; this is weaker than the association of radiological change with serum C-reactive protein. CONCLUSION: We found no significant association of sIL-2R levels with erosive change in early RA.     

Relationship between time-integrated C-reactive protein levels and radiologic progression in patients with rheumatoid arthritis

OBJECTIVE: An elevated acute-phase response is associated with increased radiologic damage in rheumatoid arthritis (RA), but development of damage in previously normal joints ("new joint involvement") has not previously been investigated. This study was undertaken to investigate the hypothesis that when there is suppression of disease activity as judged by the C-reactive protein level, new joint involvement is reduced to a greater extent than is progression in already damaged joints ("damaged joint progression"). METHODS: Three hundred fifty-nine patients with active RA were studied as part of a 5-year randomized, prospective, open-label study of disease-modifying antirheumatic drug therapy. Time-averaged CRP was calculated from samples obtained every 6 months, and patients were divided into groups with CRP values of <6, 6-<12, 12-<25, and > or =25 mg/liter. Radiographs of the hands and feet were scored by the Larsen method; a damaged joint was defined as one with a score of > or =2. RESULTS: The rank correlation between time-integrated CRP and increase in Larsen score was 0.50; the correlation increased to 0.59 for patients entering the study with disease duration of < or =2 years. The percentage of new joint involvement over 5 years varied markedly with time-integrated CRP, from 7.3% in the CRP <6 mg/liter group to 39.1% in the CRP > or =25 mg/liter group (5.4-fold increase). The percentage of damaged joint progression increased from 26.1% in the CRP <6 mg/liter group to 41.6% in the CRP > or =25 mg/liter group (1.6-fold increase). CONCLUSION: The results of this study provide further confirmation that high CRP levels over time are associated with greater radiologic progression. Although radiologic progression still occurred in both previously normal and damaged joints despite the presence of normal CRP levels, this consisted of proportionately less new joint involvement compared with damaged joint progression. These findings support the idea that disease-suppressive therapy should be instituted at an early stage in patients with RA, before erosive damage has occurred.     

Relationship between time-integrated C-reactive protein levels and radiologic progression in patients with rheumatoid arthritis

Conclusions: The results of this 5-year prospective study on the correlation of time-integrated CRP levels with radiographic progression provide further evidence that high CRP levels over time are associated with greater radiographic progression. There was less new joint involvement compared to damaged joint progression. Radiologic progression occurred in previously normal and damaged joints even with normal CRP levels. These data are consistent with those of other studies supporting early institution of therapies that can normalize CRP levels to prevent erosive damage.     

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 matrix metalloproteinase activity relating to cartilage destruction in rheumatoid arthritis

Aims: The aim of this study was to determine which matrix metalloproteinases (MMPs) are involved with C‐reactive protein (CRP) and which stage of rheumatoid arthritis (RA) correlated with MMP‐9 or MMP‐13 level. Methods: In the present clinical trial, we analysed MMP‐9 activity and MMP‐13 activity in 53 RA patients. We examined the presence of MMP‐9 and MMP‐13 in the synovium tissue and articular cartilage in RA patients by immunohistochemistry. In addition, we compared these factors and clinical Steinbrocker staging. Results: We found that MMP‐9 in blood serum correlates significantly with CRP. MMP‐13 also correlates with CRP but the coefficiency with CRP is much higher in MMP‐9 (r = 0.6694) than in MMP‐13 (r = 0.4037). MMP‐9 and MMP‐13 did not correlated with rheumatoid factor (RF). MMP‐9 level is increased in stages II and III in RA. On the other hand, MMP‐13 is increased in stages III and IV. Our results indicated that early stage RA shows high MMP‐9 release in serum while late stage RA shows high MMP‐13 release. Conclusion: MMP‐9 activity may correlate with synovium proliferation with vascularization, and serum MMP‐13 activity may correlate with the grade of joint destruction in rheumatoid arthritis.     

Factors related to radiological damage in 61 Spaniards with early rheumatoid arthritis

OBJECTIVE: To determine whether the presence of radiographic erosions at disease onset in patients with early rheumatoid arthritis (RA) is associated with clinical, serological, or genetic factors of poor outcome and whether patients with erosions only in the feet have a different pattern of presentation. METHODS: Sixty one patients with early RA (<6 months of evolution) were studied. Clinical evaluation and serological, radiological, and genetic studies were performed at disease onset and after one year. RESULTS: Forty one (67%) patients showed erosions in their hands or in their feet, or in both. Subjects with erosive RA had a higher number of swollen joints (SJN; 9 (SD 6) v. 6 (3), p=0.008), and rheumatoid factor (RF) positivity was more common (80% v. 50%, p<0.02) than those without erosions. Seven (17%) of the 41 patients in the group with erosions had erosions only in their feet. This group had a longer duration of morning stiffness (120 (60) v. 72 (52) min, p<0.005), better patient's global assessment of general health (34 (22) v. 57 (25), p< 0.05), and lower erythrocyte sedimentation rate (32 (22) v. 60 (30) mm/1st h, p <0.05) than the rest of the subjects with erosions, and none of them was in remission after one year. Remission after one year was related to a lack of cortical damage at onset and RF negativity. CONCLUSIONS: Radiological damage at disease onset is associated with a worse clinical presentation and RF positivity, which are markers of poor outcome. There is a subgroup of patients, with erosions only in their feet, whose clinical presentation is less aggressive. To identify these cases of early erosive RA, radiographs of the feet should be obtained routinely.     

Circulating dickkopf-1 and radiological progression in patients with early rheumatoid arthritis treated with etanercept

OBJECTIVE: Dickkopf-1 (Dkk-1) regulates bone remodeling in animal models of inflammatory arthritis, but its role in patients with rheumatoid arthritis (RA) remains unclear. METHODS: Baseline circulating Dkk-1 was measured in 113 patients with RA (< 3 yrs) who received etanercept (10 or 25 mg twice/week, n = 63) or methotrexate alone (n = 40) for 1 year. Progression was assessed by changes in radiological Sharp score. RESULTS: Increased Dkk-1 was associated with a higher risk of progression of bone erosion, independently of age, sex, baseline radiological damage, C-reactive protein, and disease activity in patients treated with etanercept. CONCLUSION: Dkk-1 may be an important mediator of bone erosion in patients with RA.     

Serum matrix metalloproteinase 3 is an independent predictor of structural damage progression in patients with ankylosing spondylitis

OBJECTIVE: In prospective studies, only baseline radiographic damage has been identified as an independent predictor of radiographic progression in ankylosing spondylitis (AS). Several biomarkers have been identified as independent predictors of radiographic progression in rheumatoid arthritis, however, and these may be of use in AS. This study was undertaken to analyze serologic biomarkers as predictors of radiographic progression in AS. METHODS: We measured a panel of biomarkers reflecting cartilage turnover and osteoclasis. These biomarkers were cartilage oligomeric matrix protein, human cartilage gp-39 (YKL-40), type II collagen epitopes detected by the C2C and C1,2C degradation assays and the CPII synthesis assay, aggrecan 846 epitope, osteoprotegerin, and matrix metalloproteinase 3 (MMP-3). The analysis was performed in a cohort of AS patients from the Netherlands, Belgium, and France enrolled in a longitudinal study, the Outcome Assessments in Ankylosing Spondylitis International Study. We examined 2-year radiographic progression data scored using the modified Stoke AS Spine Score (mSASSS). RESULTS: Complete data were available on 97 patients. Only the biomarkers YKL-40 and MMP-3 showed weak to moderate univariate correlation with 2-year progression. After adjustment for sex, age, disease duration, C-reactive protein level, and baseline mSASSS, only MMP-3 was significantly associated with 2-year progression (beta = 0.29, P = 0.004). Logistic regression analysis revealed MMP-3 (cutoff 68 ng/ml; odds ratio 9.4 [95% confidence interval 1.6-56]) and baseline mSASSS (cutoff 10 mSASSS units; odds ratio 18.6 [95% confidence interval 2.5-138]) as the only independent predictors of 2-year progression (cutoff 3 mSASSS units; model R(2) = 50%). MMP-3 was primarily contributory in patients who already had substantial baseline damage (>10 mSASSS units). CONCLUSION: These results indicate that MMP-3 is a significant independent predictor of radiographic progression in patients with AS, particularly in those with preexisting radiographic damage.     

Antifilaggrin antibodies in early rheumatoid arthritis may predict radiological progression

OBJECTIVE: To elucidate the possibility that autoantibodies to filaggrin, detected in patients with early RA (having a disease duration of not more than one year), may predict joint destruction assessed after five years of observation. METHODS: This is a 5 yr extension of a previous study (1) of 112 consecutive patients with early RA. Serum antifilaggrin autoantibodies were detected by immunoblotting (AFA) and by indirect immunofluorescence ("AKA"). DAS28, pain on a VAS. HAQ, and CRP were measured. Plain X-ray films were taken from hands and forefeet and a Larsen score was calculated. RESULTS: Ninety-two of the original 112 patients had baseline X-rays available and constituted the study material. At 5 year follow-up, 67 of these 92 have been assessed and for 63 of these X-rays were available. For the whole patient material, significant radiological progression, measured by Larsen scores, occurred while disease activity and function (pain VAS, DAS28, CRP, and HAQ) improved significantly over five years. The groups of patients having AFA or "AKA" at baseline had significantly (p=0.006 and p<0.001, respectively) higher Larsen scores five years later than the groups without these antibodies. No clear relation of these antibodies to disease activity or function was demonstrated, except that the group of patients with "AKA" had significantly higher median CRP (p=0,003) after five years. CONCLUSIONS: The present study shows that antifilaggrin autoantibodies may predict radiological progression. The prognostic value of these antibodies will be further evaluated in relation to other potential markers in a larger patient material.     

C-reactive protein levels in patients with rheumatoid arthritis: the impact of therapy

Summary C-reactive protein levels were measured in sera of 111 patients with rheumatoid arthritis and were compared with erythrocyte sedimentation rate. The patients were divided into six groups according to drug therapy. Comparison between the groups suggests that CRP correlates best with ESR in patients treated with penicillamine and in patients in clinical remission. Patients treated with gold, NSAID or methotrexate have a weaker correlation between the two parameters, while steroid therapy yields the poorest correlation which is not statistically significant. Our data suggest that although CRP is a sensitive index of disease activity, the specific drug taken by the patient must be considered before interpreting the results.     

血清软骨寡聚基质蛋白检测在关节炎患者中的意义研究

目的 探讨血清软骨寡聚基质蛋白(COMP)在各类关节炎患者中的差别及对类风湿关节炎(RA)软骨破坏放射学改变的早期预测价值.方法 采用酶联免疫吸附试验(ELISA)方法测定并对比分析154例各类关节炎患者血清COMP水平的差异,RA患者各项临床指标及2年后关节放射学改良SHARP(vdH-Sharp)指数评分与COMP行相关性分析.结果 与仅有滑膜损害的其他关节炎患者及正常人群比较,RA患者血清COMP显著升高(P＜0.05).骨关节炎(OA)、银屑病关节炎(PSA)患者与正常人群比较血清COMP亦有差异,而与其他滑膜关节炎患者比较差异不大.RA、OA、PSA患者间血清COMP值比较差异无统计学意义.RA患者2年随访发现COMP与患者关节X线的改良SHARP评分前后差值呈正相关(P＜0.01,r=0.848).但与初诊时的抗环瓜氨酸肽(CCP)抗体、类风湿因子(RF)、关节功能、改良SHARP评分均无相关性,与初诊时的红细胞沉降率(ESR)、C反应蛋白(CRP)、晨僵时间、关节肿胀、压痛指数相关(P＜0.05).结论 COMP在各类软骨受侵犯关节炎尤其是RA患者血清中异常增高,提示其可为RA软骨病变早期诊断及判断软骨病变进展、预后和治疗效果的一项理想指标.     

Relationship between serum RANTES levels and radiological progression in rheumatoid arthritis patients treated with methotrexate.

OBJECTIVE: The aim of this study was to evaluate the relationship between serum chemokines and the clinical and radiological response to a one-year course of methotrexate (MTX) in patients suffering from rheumatoid arthritis (RA). METHODS: Twenty out-patients suffering from active RA entered a one-year open prospective study on the effects of low dose MTX therapy. Plain radiographs of the hands and feet were taken at study entry and at the end of the follow-up, and were compared for the number of eroded joints. Serum levels of both C-X-C and C-C chemokines were obtained before the initation of MTX and after 6 and 12 months of treatment. RESULTS: The levels of serum RANTES before treatment were significantly higher in RA patients than in the controls and returned to normal levels after one year of treatment. Serum levels of the other chemokines were either in the normal range or undetectable. Twelve patients (60%) did not show any new eroded joints at the end of the follow-up period and were considered as radiological responders (RR). Serum levels of GRO-alpha and RANTES after 6 months of treatment were significantly higher among the patients with radiological progression than in RR patients. CONCLUSIONS: We observed high levels of serum RANTES in a series of RA patients during the active stage of the disease. MTX treatment significantly lowered the serum levels of RANTES, GRO-alpha and MCP-1. High levels of serum RANTES or GRO-alpha after 6 months of MTX treatment seem to be predictive of radiological erosions after one year.     

Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with early rheumatoid arthritis

OBJECTIVE: To analyze serum concentrations of matrix metalloproteinases (MMP) MMP-1, MMP-3, MMP-9, MMP-13, tissue inhibitors of MMP (TIMP) TIMP-1 and TIMP-2, and MMP/TIMP ratios in patients with early rheumatoid arthritis (RA) before and after 6 months of treatment with methotrexate (MTX). METHODS: The study group consisted of 30 patients with RA, not treated with disease modifying antirheumatic drugs or corticosteroids, with disease duration < 3 years. Twenty patients with osteoarthritis (OA) served as a control group. Analysis of serum concentrations of MMP and TIMP was based on a quantitative sandwich ELISA. RESULTS: Serum concentrations of MMP-1, MMP-3, MMP-9, and MMP-13 were higher in untreated patients with early RA than in OA patients (p < 0.001 in all cases). Serum levels of TIMP-1 and TIMP-2 dominated in the serum of RA patients compared with controls (p < 0.01 and p < 0.05, respectively). Ratios of MMP to TIMP were significantly higher in patients with early RA versus controls. Six months' treatment with MTX downregulated serum concentrations of MMP-1 (p < 0.001), MMP-3 (p < 0.001), MMP-9 (p < 0.001), MMP-13 (p < 0.01), and TIMP-1 (p < 0.05) in patients with RA. These changes were accompanied by significantly reduced ratios of MMP to TIMP. MTX treatment decreased markers of RA activity such as the number of painful and swollen joints, erythrocyte sedimentation rate, Disease Activity Score, and C-reactive protein. CONCLUSION: Patients with early RA are characterized by high serum concentrations of tissue-degrading metalloproteinases. Therapy with MTX resulted in clinical improvement and reduced serum MMP levels in patients with RA, confirming effectiveness of MTX in patients in early stages of the disease.     

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.     

Serum 25-hydroxy vitamin D levels in Egyptian patients with rheumatoid arthritis: Association with disease activity,functional disability and radiological damage

Aim of the workThe aim of this study was to examine vitamin D (VD) levels and its associations with disease activity, functional disability and radiological damage in Egyptian patients with RA.Patients and methodsThis study included 150 RA patients and 150 matched controls. All participants were not receiving VD supplements. Serum 25(OH)-D levels were measured in all participants. Serum 25(OH)-D levels at 30 and 20 ng/ml were the cut-off values for VD insufficiency and deficiency, respectively. Associations of 25(OH)-D levels with disease activity score associated with C-reactive protein (DAS-28-CRP), functional disability assessed by the Health Assessment Questionnaire (HAQ) and radiological damage as assessed by the modified Larsen method were considered.ResultsLow VD levels were frequent in RA patients (22 ± 9.2 ng/ml) compared to the control (28.7 ± 9.6 ng/ml) (p < 0.001); 42.7% had VD levels <20 ng/ml and was <30 ng/ml in 80.7%. RA patients with VD deficiency were older, more frequently females and had higher swollen joint count (SJC), tender joint count, visual analogue scale for pain and DAS28-CRP. Only SJC and DAS28-CRP remained significant following the multivariate analysis (p = 0.029, p = 0.007 respectively), while rheumatoid factor, anti-cyclic citrullinated peptide antibodies, medications used, HAQ and radiologic score had no association with VD levels.ConclusionsVitamin D insufficiency and deficiency are common among Egyptian RA patients and are associated with decreased sun exposure. VD deficiency was related to older age, female gender, swollen joint count and disease activity. Vitamin D levels had no relation with RA functional disability and radiological damage.     

Reduced chemokine and matrix metalloproteinase expression in patients with rheumatoid arthritis achieving remission

OBJECTIVE: To quantify the changes in synovial expression of mediators of macrophage chemotaxis, matrix degradation, and macrophage infiltration in the synovial membrane of patients with rheumatoid arthritis (RA) achieving American College of Rheumatology (ACR) defined remission and radiological arrest. METHODS: Knee synovial biopsies were taken from a selected group of 18 patients with RA before and after treatment and immunostained with antibodies specific for CD68; the chemokines macrophage inflammatory protein (MIP)-1a and monocyte chemoattractant protein (MCP)-1; matrix metalloproteinases (MMP-1 and 3) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMP-1 and 2); as well as isotype-specific negative controls. Immunostaining was quantified using a computer assisted color video image analysis system. Radiographs were performed before and after treatment and the Larsen score determined. Patients were arbitrarily divided into 2 groups: the radiological arrest group (defined as change in Larsen score pound 5 from baseline) and radiological progressors (defined as change in Larsen score > 5). Patients were classified according to ACR response criteria. RESULTS: In the 8 patients who achieved ACR defined remission, there were tendencies toward reductions in the synovial lining layer (LL) expression of MIP-1a by 36% (p = 0.1) and MCP-1 by 48% (p = 0.1). Significant reductions occurred in the expression of MMP-1, by 53% in the LL (p = 0.008) and 59% in synovial sublining layer (SL) (p = 0.02) and MMP-3, by 76% in LL (p = 0.02), and 72% in SL (p = 0.008), but not in TIMP expression. In this group of patients there were reductions in MMP:TIMP ratios, in particular the MMP-1:TIMP-1 ratio in the LL (p = 0.05), MMP-3:TIMP-1 ratio in the LL (p = 0.05) and SL (p = 0.008), and MMP-3:TIMP-2 ratio in the LL (p = 0.04) and SL (p = 0.08). In this group of patients CD68+ macrophage infiltration was significantly reduced in the LL by 59% (p = 0.008) and in the SL by 52% (p = 0.008), which corresponded with the reductions in chemokine expression. In the remaining 10 patients who did not achieve full remission there were no significant changes in the variables studied. In the group achieving ACR 50% or 70% response there was a reduction in CD68 expression that approached significance (p = 0.06 in LL and SL), but there was no significant change in the other variables. There were no significant changes in the patients with an ACR 20% response. In the radiological arrest group (12 patients) there was a 41% reduction in LL expression of MIP-1a (p = 0.05) and MMP-1 (p = 0.06). Reductions in MMP:TIMP expression were also noted, in particular in MMP-1:TIMP-1 expression in the LL (p = 0.04) and MMP-3:TIMP-1 in the SL (p = 0.01). There were corresponding reductions in CD68 expression by 49% (p = 0.009) in LL and by 42% (p = 0.0005) in SL. In the radiological progressors (6 patients) there were no significant reductions in mediator expression. CONCLUSION: In RA, ACR defined remission is associated with reductions in MMP-1 and 3 expression, with a corresponding reduction in macrophage infiltration and a tendency to reduction in MIP-1a expression. Radiological arrest is associated with reductions in MMP-1 expression, and significant reductions in macrophage infiltration, MIP-1 expression, and MMP:TIMP ratio.