Calprotectin levels in rheumatoid arthritis and their correlation with disease activity: a meta-analysis

Objective: We evaluated the relationship between calprotectin levels and rheumatoid arthritis (RA), and the correlation between plasma/serum calprotectin and RA activity.

Methods: We searched PUBMED, EMBASE, and Cochrane databases and performed meta-analyses comparing plasma/serum or synovial fluid calprotectin levels in RA patients and controls, and correlation coefficients between calprotectin levels and disease activity for 28 joints (DAS28) as well as C-reactive protein (CRP) in RA patients.

Results: Sixteen studies including 849 RA patients and 266 controls were available for meta-analysis. Meta-analysis showed that calprotectin levels were significantly higher in the RA group than in the control group (SMD = 2.337, 95% CI = 1.544–3.130, p < 1.0 × 10^–8). Stratification by rheumatoid factor (RF) status revealed significantly elevated calprotectin levels in the RF-positive RA group compared to that of the RF-negative RA group (SMD = 0.574, 95% CI = 0.345–0.804, p = 9.2 × 10^–7). Meta-analysis of correlation coefficients identified a significant positive correlation between calprotectin levels and CRP or DAS28 (correlation coefficient for CRP = 0.566, 95% CI = 0.512–0.615, p < 1.0 × 10^–8; correlation coefficient for DAS28 = 0.438, 95% CI = 0.269–0.518, p = 2.5 × 10^–6). Calprotectin levels in synovial fluid were significantly higher in the RA group than in the control group (SMD = 2.891, 95% CI = 1.067–4.715, p = 0.002).

Conclusions: Our meta-analysis demonstrates that circulating and synovial fluid calprotectin levels are high in patients with RA, and that circulating calprotectin levels positively correlate with RA activity.     

类风湿性关节炎患者血脂水平分析

目的 通过检测类风湿性关节炎(rheumatoid arthritis,RA)患者同型半胱氨酸(homocysteine,HCY)、脂蛋白(a) [lipoproteins,LP(a)]、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)及白细胞介素17(interleukin-17,IL-17)和白细胞介素6(interleukin-6,IL-6)的水平变化,探讨RA患者是否是动脉粥样硬化的高风险人群.方法 研究对象共92例,其中病例组60例,健康对照组32例(对照组),采用循环酶法检测HCY;免疫比浊法检测LP(a);免疫抑制直接法检测HDL-C及LDL-C的水平;流式液相多重蛋白定量技术(cytometric bread array,CBA)检测IL-17和IL-6的水平.结果 病例组血清中HCY、IL-17、IL-6、LDL-C的水平明显高于对照组,差异具有统计学意义(P＜0.05),病例组血清HDL-C的水平低于健康对照组(P＜0.05),病例组LP(a)水平与对照组比较差异无统计学意义(P＞0.05).另外,男性RA患者LP(a)的水平高于女性(P＜0.05).结论 RA患者的炎症反应对脂质代谢有一定的干扰作用,RA患者可能是动脉粥样硬化的易感人群,提示临床在治疗RA的同时,也应考虑预防动脉粥样硬化的发生.     

The relationship between serial measures of disease activity and outcome in rheumatoid arthritis

Disease activity was measured annually over a median periodof 7 years (range 5–9) in a cohort of 127 patients withrheumatoid arthritis. The measurements were plotted, and thearea under the resultant curve measured. The relationship ofserial measures of disease activity (area under the curve) tooutcome (measured radiologically, functionally and by globalassessment) was investigated. A significant correlation wasfound between persistent disease activity and radiographic deterioration.Similar results were found for functional outcome, as measuredby Steinbrocker grade, health assessment questionnaire scoreor global assessment (by analogue score). Single measures ofdisease activity did not predict outcome. Although imprecise,current methods of measuring disease activity in RA, if measuredserially, are valuable in predicting outcome over a 5–10year period.     

Serum levels of C1 subunits in rheumatoid arthritis

Modifications of radial immunodiffusion and of hemolytic assays of C1q are described, which enable the results of these assays to be in agreement with those obtained by hydroxyproline assay. Using these assays, we show that C1q serum levels are significantly increased in rheumatoid arthritis (RA) and that the excess C1q levels in this disease are not accompanied by increased levels of C1r and C1s. Active RA is therefore characterized by increased levels of hemolytically active C1q that has a physiologically active stem region unbound to C1r and C1s.     

Serum levels of interleukin-6 and tumour-necrosis-factor-alpha are not correlated to disease activity in patients with rheumatoid arthritis after treatment with low-dose methotrexate

Abstract. Cytokines are major mediators of inflammatory responses in rheumatoid arthritis. Some of them have been shown to correlate with the disease activity and thus are proposed to be used for monitoring patients. Therefore the effects of a low-dose therapy with methotrexate on serum concentrations of interleukin-6 (IL-6) and tumour-necrosis-factor-alpha (TNF-α) were examined in eight patients with seropositive rheumatoid arthritis. Serum levels of IL-6 and TNF-α were significantly elevated in patients compared to healthy controls. Before the onset of MTX treatment IL-6 concentrations were correlated to the c-reactive protein ( P < 0·05) but the correlation was abolished after treatment. For TNF-α no correlations neither before nor after treatment were observed. Both cytokines remained substantially elevated after MTX treatment despite a clear reduction in disease activity. Thus we suggest that one of the effects of MTX might be the inhibition of some of the actions of IL-6 and TNF-α.     

Serum progranulin level is associated with disease activity following orthopedic surgery in rheumatoid arthritis patients

BackgroundFew studies have focused on the ability of progranulin to predict postoperative disease activity in rheumatoid arthritis (RA) patients who have undergone surgery. This study evaluated serum progranulin levels in active RA patients and analyzed its relationship with postoperative disease activity.MethodsOne hundred thirty-two patients with active RA and 72 healthy subjects were included in this study. Serum progranulin was measured, and clinical data were collected. The postoperative 1-year Disease Activity Score in 28 joints calculated with C-reactive protein (DAS28-CRP) scores was evaluated as an indicator of disease activity. The predictive value of progranulin in postoperative 1-year disease activity in RA patients was also analyzed.ResultsSerum progranulin was significantly associated with the postoperative 1-year RA disease activity. The mean serum progranulin level in patients with a high disease activity was significantly higher than that of RA patients with low-to-moderate disease activity (54.2 ± 10.6 ng/mL vs. 46.7 ± 8.8 ng/mL). Serum progranulin was also evaluated as an independent predictive factor for postoperative 1-year RA disease activity in multivariate analysis (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.02–8.85).ConclusionsSerum progranulin levels may be a promising indicator of postoperative disease activity in RA patients who underwent orthopedic surgery.     

RA患者免疫功能失衡与疾病活动情况的关系研究

目的探讨类风湿关节炎(RA)患者免疫功能失衡与患者疾病活动程度的关系。方法选取我院类风湿免疫科确诊的RA患者90例(RA组)、健康体检志愿者60例作为对照组;检测两组对象外周血中Th17细胞、调节性T细胞(Treg)、血清γ干扰素(IFN-γ)、白细胞介素-4(IL-4)、C反应蛋白(CRP)、血沉(ESR),并分析Th17细胞、Treg、IFN-γ、IL-4与患者关节疼痛数目、类风湿关节炎病情评价(DAS28评分)的相关性。结果 RA组患者的Th17细胞、血清IFN-γ均高于对照组(P<0.05),RA组患者的Treg细胞低于对照组(P<0.05);RA组患者的血清CRP、ESR水平均高于对照组(P<0.05);DAS28评分>5.1分RA患者的Th17细胞、血清IFN-γ均高于≤5.1分的患者(P<0.05),DAS28评分>5.1分RA患者的Treg细胞低于≤5.1分的患者(P<0.05);RA患者的Th17细胞、血清IFN-γ与DAS28评分、压痛关节数目呈显著正相关(P<0.05),RA患者的Treg细胞与DAS28评分、压痛关节数目呈显著负相关(P<0.05)。结论 RA患者T细胞及免疫学因子失衡可能与患者疾病活动程度、病情严重程度有关。     

Soluble CD206 plasma levels in rheumatoid arthritis reflect decrease in disease activity

Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and infiltration by activated macrophages. TNFα is a central mediator in this process. The mannose receptor, CD206, is a scavenger receptor expressed by M2_A-macrophages and dendritic cells. It is involved in collagen internalization and degradation. The soluble form has been suggested as a biomarker of M2_A-macrophage activation. The aim of this study was to investigate sCD206 plasma levels in early RA patients initiating anti-TNFα treatment. Plasma levels of sCD206 were measured by ELISA in samples from 155 early RA patients with an average symptom duration of 3 months. Patients were randomized to 12 months’ methotrexate and placebo (PLA) or methotrexate and adalimumab (ADA) treatment, followed by open-label treatment with disease-modifying anti-rheumatic drugs (DMARD) and if needed, ADA. Disease activity was assessed at baseline and after 3, 6, 12 and 24?months. Baseline plasma level of sCD206 in treatment naïve RA patients was 0.33?mg/L (CI: 0.33–0.38?mg/L) corresponding to the upper part of the reference interval for healthy controls (0.10–0.43?mg/L). In the PLA group, sCD206 levels decreased after 3?months, but did not differ from baseline after 6?months. In the ADA group, however, levels remained lower than baseline throughout the treatment period. In conclusion, initially, plasma sCD206 in early RA patients decreased in accordance with disease activity and initiation of DMARD treatment. Treatment with anti-TNFα preserved this decrease throughout the study period.     

类风湿关节炎患者血清IL-35的水平及其与疾病活动度的关系

目的探讨类风湿关节炎(RA)患者血清IL-35表达水平与疾病活动度的相关性。方法选取确诊RA患者118例,分为活动期组62例和缓解期组56例。同时选取90例健康人作为对照,ELISA法检测RA患者及对照者血清IL-35水平,实时荧光定量PCR检测外周血单个核细胞(PBMC)中IL-35亚基EBI3和P35 mRNA表达水平。分析血清IL-35水平与DAS28评分、C反应蛋白(CRP)、红细胞沉降率(ESR)、类风湿因子(RF)、关节肿胀数(SJC)和关节压痛数(TJC)等的相关性。结果活动期组RA患者血清中IL-35浓度(38.09±16.90)pg/m L显著低于对照组[(82.25±15.82)pg/m L,P0.01)]和缓解期组[(72.96±11.74)pg/m L,P0.01)];依据DAS28评分将活动期组RA患者分为轻度、中度和重度组,血清IL-35水平(pg/m L)在3组中依次降低(轻度60.95±7.31,中度39.68±9.51,重度28.02±9.16),轻度组与中度或重度组间差异具有统计学意义(P0.05)。活动期组和缓解期组患者血清IL-35水平与SJC、CRP和DAS28评分呈负相关性(P0.05),与ESR、TJC、RF无相关性。PBMC中P35 mRNA在RA活动期组中显著降低,低于健康对照组和缓解期组(0.47±0.18 vs 1.91±1.121.82±0.53,P0.01),但EBI3 mRNA在活动期组(1.62±0.68)、缓解期组(1.48±0.77)及对照组(1.86±1.21)中差异无统计学意义(P0.05)。结论活动期组RA患者血清IL-35水平显著下降,且伴随P35 mRNA水平下降,并与RA疾病活动度密切相关,可作为RA疾病活动度评价的潜在指标。     

Serum copper/zinc superoxide dismutase levels in patients with rheumatoid arthritis

Rheumatoid arthritis is characterized by a chronic hypertrophic synovitis leading to destruction of connective tissue and functional damage of cartilage and bone structures. Reactive oxygen species play an important role in tissue injury in this disease. To clarify the role of the cellular antioxidant system in the protection against oxygen free radicals, we examined the levels of copper/zinc superoxide dismutase in the sera of patients with rheumatoid arthritis. We used an enzyme-linked immunosorbent assaywhich determines the concentration of copper/zinc superoxide dismutase indepedently from its enzymatic activity. We found that patients with rheumatoid arthritis have higher serum copper/zinc superoxide dismutase levels than control subjects. Copper/zinc superoxide dismutase also correlated positively with serum levels of both neopterin and rheumatoid factor, sensitive markers for disease activity in rheumatoid arthritis. These results support the hypothesis that the increased amount of copper/zinc superoxide dismutase is probably inadequate to exert an effective antioxidant protection but can result in a pro-inflammatory, pathogenic effect enhancing tissue damage. Furthermore, copper/zinc superoxide dismutase might be used as a marker of inflammatory activity in rheumatoid arthritis.     

Serum interleukin 2 levels in patients with rheumatoid arthritis and correlation with insulin sensitivity

Interleukin 2 (IL-2), a Th1 lymphocyte-derived cytokine, is thought to play an important role in the pathogenesis of type 2 diabetes and rheumatoid arthritis (RA). The aim of our study was to evaluate changes in serum IL-2 levels and their correlation with glucose metabolism abnormalities, such as insulin resistance, in patients with RA. Thirty-six subjects with varying degrees of disease activity and 20 healthy age-, sex- and body mass index-matched control individuals were evaluated. Patients with any causes of peripheral insulin resistance were excluded. After a 12-h overnight fast, fasting insulin levels, homeostatic model assessment-insulin resistance (HOMA-IR) estimated insulin sensitivity, and serum IL-2 levels were significantly higher in all patients with RA than in the control individuals. Fasting insulin, HOMA-IR scores and IL-2 levels were correlated in the RA group. This study showed that patients with RA have altered IL-2 regulation, and that there was a significant correlation between serum IL-2 levels and insulin sensitivity.     

Serum levels of parathyroid hormone and markers of bone metabolism in patients with rheumatoid arthritis. Relationship to disease activity and glucocorticoid treatment.

OBJECTIVE: To evaluate the influence of inflammatory activity and glucocorticoid (GC) treatment on serum parathyroid hormone (s-PTH) and bone metabolism in patients with rheumatoid arthritis (RA). Furthermore, in patients with active RA, to examine the PTH secretion and Ca2+ set point before and after treatment with GC. METHODS: A range of biochemical markers of bone metabolism and calcium homeostasis were measured in 95 patients with definite RA stratified into groups according to disease activity and GC treatment. In a subgroup of 12 patients with active disease, initiating slow-acting-anti-rheumatic-drugs (SAARDs) +/- GC, the PTH secretion and calcium set point were evaluated by use of the Cica clamp technique before and after 1 month of treatment. RESULTS: S-osteocalcin, s-total alkaline phosphatase (s-TAP) and s-carboxyterminal cross-linked telopeptide of type I collagen (s-ICTP) were elevated in all groups. The levels of urine pyridinoline (Pyr) and s-albumin-corrected calcium (s-AlbCorrCa2+) were elevated in patients with active disease and patients treated with GC. S-PTH and s-phosphate were within normal ranges. S-TAP, s-ICTP, Pyr and s-AlbCorrCa2+ correlated positively with indices of disease activity. In the subgroups undergoing the Cica clamp technique, no difference in PTH responsiveness of B-Ca2+ was unveiled. CONCLUSION: Neither active disease nor GC therapy appears to induce secondary hyperparathyroidism, nor is there an alteration in PTH responsiveness of B-Ca2+ in patients with RA. The increased levels of markers of type I collagen metabolism (s-ICTP, Pyr) and s-AlbCorrCa2+ in patients with active disease and patients treated with GC may be a result of increased degradation in synovium, cartilage and bone due to the inflammatory process.     

高频超声对于类风湿关节炎疾病活动性的研究应用

类风湿关节炎是临床常见的以关节滑膜炎症为主要表现的自身免疫性疾病,临床治疗依据疾病活动度制定相关治疗方案,疾病活动度是评估药物疗效和病程的重要指标,目前评估疾病活动度最常使用的是DAS28评分,由于该评分资料收集繁琐,计算过程较为复杂且需要等待血液学检测结果,在日常工作尤其是门诊工作中其应用受到极大的限制;近些年来,高频超声各项技术在类风湿关节炎的诊疗中发挥重要作用,本文就高频超声各项技术在类风湿关节炎疾病活动度方面的应用研究做一概述。     

Serum collagenase-like peptidase activity in rheumatoid arthritis and systemic lupus erythematosus

Collagenase-like (CL) peptidase activity in serum, which was measured using a newly synthesized substrate, (succinyl-Gly-Pro-Leu-Gly-Pro)-4-methylcoumaryl-7-amide, was significantly lower in patients with advanced rheumatoid arthritis or with systemic lupus erythematosus than that in normal controls. Decrease of the serum enzyme activity was more pronounced in systemic lupus erythematosus. No significant change in serum CL-peptidase activity was found in other connective tissue diseases such as mixed connective tissue disease and Sj?gren's syndrome.     

Edaravone inhibits the disease activity in rheumatoid arthritis

A male patient with rheumatoid arthritis (RA) developed acute stroke and was treated with the free radical scavenger, edaravone. Polyarthralgia improved with a reduction in serum C-reactive protein concentration soon after the start of edaravone administration. The disease activity score 28 (DAS28) also decreased. Edaravone appears to be effective for the control of RA. The usefulness of this potentially novel therapeutic agent should be tested in a well designed randomized controlled trial.     

Serum kynurenine in rheumatoid arthritis

The concentration of kynurenine has been measured in the serum of patients with rheumatoid arthritis and in a control group. The mean serum concentration was 2.27 +/- 0.688 mug/ml for patients with rheumatoid arthritis and 2.95 +/- 0.825 mug/ml for the control group.KYNURENINE: creatinine clearance ratios were higher in the rheumatoid arthritis than in the control group. These data suggest that the increased urinary excretion of kynurenine by patients with rheumatoid arthritis is due at least in part to renal factors.