Serum Krebs von den Lungen-6 and lung ultrasound B lines as potential diagnostic and prognostic factors for rheumatoid arthritis–associated interstitial lung disease

Introduction

Rheumatoid arthritis (RA)–associated interstitial lung disease (ILD) (RA-ILD) is a serious systemic RA manifestation with high mortality that needs proper, accurate, and sensitive assessment tools.

Objectives

Firstly, evaluate serum Krebs von den Lungen-6 (KL-6) levels and lung ultrasound B lines (LUS B lines) score in RA-ILD correlating them with the severity of ILD assessed by high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs). Secondly, determine cut-off values for LUS and KL-6 in RA-ILD assessment and outcome prediction.

Methods

A case-control study included seventy-five RA-ILD patients with an equal number of matched RA patients without ILD. Clinical assessment includes DAS-28 and PFTs, laboratory assessment of serum KL-6 by latex-enhanced immunoturbidimetric assay, and radiological evaluation of ILD using semiquantitative CT grade and LUS B lines.

Results

RA-ILD patients had significantly higher serum KL6 compared to those without ILD (1025.5?±?419.6 vs. 237.5?±?51.9, p?≤?0.001). Serum KL6 was positively correlated with HRCT and LUS scores (r?=?0.93, r?=?0.97, respectively) with negative correlation with FVC% and FEV1% (r?=???0.93, r?=???0.91, respectively). LUS was positively correlated with KL6 and HRCT (r?=?0.97, r?=?0.944, respectively) while, negatively correlated with PFTs. Cut-off values of KL6 and LUS were 277.5 U/ml and < 5.5, with AUC 0.878 and 1, sensitivity 86.7% and 100%, and specificity 88% and 100%, respectively.

Conclusions

The non-invasive, radiation-free LUS with a score < 5.5 combined with serum KL6 could be helpful for RA-ILD assessment correlating with HRCT and disease severity. Serum KL6 combined with LUS is important new and potential prognostic factor predicting poor outcomes in RA-ILD. Further large-scale, multi-center, and prospective studies are needed to confirm these findings.

Key Points

? Combination of the non-invasive, radiation-free LUS with a score < 5.5 and serum KL6 levels of 277.5 U/ml is recommended as prognostic tools for RA-ILD.

? Easily obtainable tests such as serum KL-6, inflammatory markers, and LUS are sensitive for assessing RA-ILD and the risk of poor outcomes in patients with RA-ILD.

? RA-ILD patients with higher KL6 levels, higher LUS scores had a poor prognosis with short survival.

? LUS B lines could be used as the first imaging tool for the evaluation of RA-ILD decreasing the risk of HRCT radiation exposure in asymptomatic or mild RA-ILD patients.

     

High-resolution CT and pulmonary function tests in rheumatoid arthritis patients with subclinical interstitial lung disease in Kuwait

BackgroundInterstitial lung disease (ILD) is a frequent extra-articular manifestation of RA and can cause significant morbidity and mortality.Aim of the workTo characterize and define the frequency of radiological and functional abnormalities capable of identifying “subclinical” RA-ILD with particular concern to the effect of methotrexate (MTX) therapy.Patients and methodsSixty patients with RA were recruited with no respiratory manifestations. They were classified into two groups: group 1 included 35 patients receiving MTX and group 2 included 25 patients receiving only nonsteroidal anti-inflammatory drugs. Patients were also classified according to chest high resolution CT (HRCT) as RA-ILD or RA-noILD. Pulmonary function test (PFT) abnormalities were also used to further characterize occult respiratory defects.Results38.3% of RA patients had subclinical ILD (25% in group 1 and 13.3% in group 2), while 61.7% were RA-no ILD. The percentage of patients with RA-ILD was insignificantly more in group 1 than group 2 (42.9% and 32% respectively). HRCT score revealed minimal to mild involvement in both groups. Long-standing RA with mean articular duration >50 months carries a significant risk for ILD. Other variables as age, gender, smoking, disease activity or rheumatoid factor seropositivity were not significant risk factors for development of RA-ILD.ConclusionsLung involvement should always be considered in patients with RA particularly those on MTX therapy even in the absence of chest symptoms. A tight control by PFTs, chest radiography and/or HRCT is necessary. Further studies evaluating the potential effect of MTX on progressive ILD with RA are needed.     

类风湿关节炎合并肺间质病变的临床特点

目的 分析类风湿关节炎（RA）合并肺间质纤维化（ILD）患者的临床特点,为尽早发现和诊断RA-ILD提供有价值的临床信息.方法 回顾性分析2008年1月～2009年1月于我院就诊的40例RA-ILD患者与42例未合并ILD的RA患者的临床资料,并对两组患者的临床资料加以比较.结果 RA-ILD组患者多数以咳嗽为首发症状,全部患者高分辨率CT检查均存在不同程度的ILD表现.RA-ILD组患者的病程、晨僵时间长于未合并ILD的RA组患者（P＜0.05）.RA-ILD患者组的DAS28评分、血沉、C反应蛋白、抗环瓜氨酸（CCP）抗体、Ro-52阳性率高于未合并ILD的RA组患者（P均＜0.05）.结论 RA-ILD患者多数以咳嗽为首发症状,高分辨率CT能较早的提示ILD并评价其严重程度.RA病程、活动性、炎性指标、抗CCP抗体及抗Ro-52可能是与RA-ILD密切相关的重要指标.     

Retrospective study of the clinical characteristics and risk factors of rheumatoid arthritis-associated interstitial lung disease

This study aims to explore the clinical characteristics and risk factors of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). This is a retrospective study of 550 patients with RA. All patients underwent chest high-resolution computed tomography (HRCT) scanning. (1) Two hundred thirty-seven out of five hundred fifty (43.1%) patients with RA were diagnose with ILD. 13.5% ILD occurred before RA onset, 69.6% ILD occurred within 10 years of RA onset, and 16.9% ILD occurred more than 10 years after RA onset. (2) The most common chest CT characteristics of RA-ILD included reticular patterns (57.8%), pleural thickening (57%), ground-glass attenuation (53.2%), followed by interlobular septum thickening, nodules, emphysematous bullae, honeycombing, and bronchiectasis. The proportion of the UIP pattern and NSIP on HRCT was 18.6% and 57.8%. (3) RA-ILD was often associated with other lung lesions, including pleural disease, bronchiectasis, and pulmonary hypertension. (4) the comparisons between RA with ILD and RA without ILD showed that male, smoking, age, disease duration, number of swelling joints, globulin levels, erythrocyte sedimentation rate, C-reactive protein levels, lactate dehydrogenase, the positive rate of rheumatoid factor (RF) and the absolute value of RF, forced vital capacity, forced expiratory volume in 1 s, and carbon monoxide diffusion rate, were statistically different (P < 0.05). Logistic regression analysis showed that age, smoking, elevated lactate dehydrogenase, and RF positive were closely correlated to RA-ILD. RA-ILD occurs more often within 10 years of RA onset and coexists with other lung lesions. The elevated lactate dehydrogenase, RF positive, smoking, and advanced age are closely correlated with RA-ILD.     

Rheumatoid arthritis-related interstitial lung disease (RA-ILD): methotrexate and the severity of lung disease are associated to prognosis

Interstitial lung disease (ILD) is a severe rheumatoid arthritis (RA) manifestation. The worst survival has been associated with usual interstitial pneumonia (UIP) definitive pattern in high-resolution chest tomography (HRCT) scans. Moreover, the use of methotrexate in RA-ILD is controversial. Our aim was to evaluate prognostic factors including methotrexate in an RA-ILD cohort and their association with survival. RA-ILD patients referred for medical evaluation and treatment at a single center were included. At the baseline, pulmonary function tests were carried out and a HRCT was obtained. A radiologist evaluated the ILD tomographic pattern and the extent of lung disease. Patients were considered as receiving methotrexate therapy if this drug was specifically prescribed for the treatment of RA-ILD at the beginning of follow up. Seventy-eight patients were included. UIP definite pattern in HRCT was not associated to worse survival. Variables associated with mortality reflected the severity of lung disease. Treatment with methotrexate was associated with survival (HR 0.13, 95% CI 0.02–0.64); older patients had worse prognosis (HR 1.04, 95% CI 1.003–1.09). After adjusting for confounding variables, methotrexate was strongly associated with survival. Methotrexate treatment during follow up was associated with survival. The severity of lung disease and not the tomographic pattern is associated with mortality; older patients had worse prognosis.     

类风湿关节炎相关肺间质病变的危险因素、临床和影像学特点

目的分析类风湿关节炎(RA)相关肺间质病变(RA-ILD)的危险因素、临床特点及影像学特征,以利于早期诊断、合理治疗。方法回顾性总结233例住院诊治RA患者的临床资料,比较RA-ILD组与单纯RA组的临床特点。结果 RA-ILD的发生率为20.6%(48/233)。RA-ILD组患者平均发病年龄、平均病程、大量吸烟率、类风湿因子水平、抗环瓜氨酸肽抗体阳性率、抗核周因子阳性率和抗角质蛋白抗体阳性率均高于单纯RA组,差异有统计学意义(P<0.05);双手X线Ⅰ期改变百分数较单纯RA组低,差异有统计学意义(P<0.05)。26例(54.17%)RA-ILD患者有呼吸系统临床表现,包括咳嗽、活动后呼吸困难和肺部爆裂音;22例(45.83%)通过肺高分辨CT(HRCT)和/或肺功能(PFT)检查诊断。HRCT改变依次为纤维条索/网格影33例(68.75%)、斑片渗出影/实变影21例(43.75%)、磨玻璃影15例(31.25%)、蜂窝状影11例(22.92%)以及胸腔积液5例(10.42%);PFT均有弥散功能减退。结论 RA-ILD发病年龄较大、病程较长,与疾病严重性相平行,而与疾病活动性不相关。HRCT及PFT对早期诊治RA-ILD有重要价值。     

Quality of sleep in rheumatoid arthritis patients: Relationship with disease activity,depression and functional status

Aim of the workTo assess sleep quality in Egyptian patients with rheumatoid arthritis (RA) and its relationship with disease activity, depression and functional status.Patients and methodsThis cross-sectional study included 133 RA patients and 76 age and sex matched controls. Sleep using the Pittsburg Sleep Quality Index (PSQI), Beck depression inventory (BDI), functional status using health assessment questionnaire (HAQ), visual analogue scale-pain (VAS), and disease activity score (DAS28) were assessed.ResultsPatients were 125 females and 8 males with a mean age of 42.5 ± 9.5 years and disease duration of 3.9 ± 1.3 years. 76 age and sex matched control were also included. Poor sleep quality was detected in 54.1% of patients. Patients had significantly higher scores in the subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, day-time dysfunction domains and in terms of the total PSQI score compared to the control (p < 0.05). A significant difference was found between RA patients with poor sleep quality and those with good sleep quality as regards marital status, HAQ, erythrocyte sedimentation rate (ESR), VAS, DAS28, morning stiffness duration, anti-cyclic citrullinated peptide (anti-CCP) (p < 0.05), and the BDI (p < 0.001). The multivariate regression analysis found that disease activity, functional disability and depression were predictors for poor sleep quality (p = 0.04, p = 0.01 and p < 0.001; respectively).ConclusionThe sleep quality is impaired in RA patients. The poor sleep quality is associated with disease activity, depression and functional disability. Systemic psychiatric screening, holistic assessment and targeted interventions are required to improve sleep quality and quality of life.     

Interstitial lung disease in Egyptian patients with rheumatoid arthritis: Frequency,pattern and correlation with clinical manifestations and anti-citrullinated peptide antibodies level

Introduction

Interstitial lung disease (ILD) represents 13% of the overall mortality in rheumatoid arthritis (RA) patients.

Disease characteristics in high versus low titers of rheumatoid factor or anti-citrullinated peptide antibody in rheumatoid arthritis patients

Aim of the workTo evaluate the impact of the level of rheumatoid factor (RF) or anti-citrullinated peptide antibody (ACPA) positivity on the clinical manifestations, disease activity, functional status, and treatment strategy among rheumatoid arthritis (RA) patients.Patients and methodsIn this study, 120 consecutive RA patients were grouped according to the level of RF or ACPA positivity. Group 1: patients with low positive RF or ACPA and Group 2: those with high titer. Disease activity score (DAS28) and functional status using modified health assessment questionnaire (MHAQ) were assessedResultsThe patients mean age was 46.9 ± 10.9 years and female to male ratio was 7:1. 44 (36.7%) patients had low positive RF/ACPA titers, 59 (49.2%) had high titers and 17 (14.2%) had negative RF/ACPA and were excluded. Patients' global assessment of disease activity was significantly higher among patients with high RF/ACPA titer compared to those with low titer (p = 0.04) and MHAQ tended to be higher (p = 0.058). Subcutaneous nodules (p = 0.037) were more frequent among those with high RF/ACPA titer. The cumulative (p = 0.012) and the current (p = 0.006) steroid doses administered both turned out to be significantly higher in the high positive RF/ACPA patient group.ConclusionPatients with high titer RF and\or ACPA have factors that may contribute to poor outcome as the presence of reduced functional status which indicated by the higher MHAQ score, the need for higher daily and cumulative steroid doses as an indirect indicator of increased disease activity and in turn poor outcome.     

Pregnancy outcome in a cohort of Egyptian women with rheumatoid arthritis

BackgroundFemale patients with rheumatoid arthritis (RA) can have successful pregnancies. However, those who experience a higher disease activity during pregnancy and require continued treatment have a potential risk of maternal and neonatal complications.Aim of the workTo assess pregnancy outcome (adverse maternal and neonatal outcomes) in an Egyptian cohort of female RA patients.Patients and methodsThiscross-sectional study involved 200 female RA patients and 100 healthy age-matched controls. All were subjected to detailed gynecological history including: number of pregnancies, miscarriage, mode of delivery, maternal complication (gestational diabetes and preeclampsia), fetal complication (prematurity, low birth weight ‘LBW’ and congenital anomalies) and medicationsused during pregnancy. The disease activity score (DAS28) was assessed pre-conception and in each trimester.ResultsPatients had significantly lower number of pregnancies (p = 0.002) and deliveries (p = 0.001) and higher incidence of miscarriages (p = 0.022) compared to controls. Delivery by Cesarean section (CS) was higher inpatients (p = 0.001) with an increased risk of preeclampsia (p = 0.042). Both the antenatal and natal DAS28 significantly correlatedwith abortions, deliveries by CS and LBW (p = 0.005, p = 0.004 and p < 0.001, respectively). Pre-conceptional methotrexate use significantly correlated with the number of abortions (p = 0.02). Corticosteroid use during pregnancy was related to LBW of newborns (p = 0.03).ConclusionPregnant RA patients have higher frequency of abortion, delivery by CS, preeclampsia and LBW of newborns; especially those having higher disease activity and/ortreated with potentially harmful medications. It is crucial to educate female RA patients about these risks and they should be considered as high-risk pregnancy and followed accordingly.     

Pulmonary involvement in early rheumatoid arthritis patients

Pulmonary involvement in rheumatoid arthritis (RA) is common and can be due to the disease itself as well as to the therapies used to treat it. The purpose of this study was to disclose the pulmonary involvement in early RA patients not more than 2 years disease duration using the computed tomography (CT) as well as the pulmonary function tests as ways of pulmonary involvement assessment. Forty patients aged 37.6 ± 10.3 with early rheumatoid arthritis not more than 2 years of disease duration were recruited for the study. All patients were assessed clinically for their RA with DAS28, which was utilized for disease activity determination. Ten percent of our patients were found to be clinically involved by interstitial lung disease (ILD), where 27% have abnormal HRCT finding and 32.5% with abnormal PFT. Predilection for clinically manifest ILD was evident in active RA patients with high DAS28 score, seropositive RA patients, and in patients receiving steroids and anti-TNFα therapy. ILD occurs early in the course of RA, with more predilection for clinically active RA disease.     

Detection of hearing loss in rheumatoid arthritis patients using extended high frequency audiometry: Is it related to disease activity and severity?

Aim of the workTo evaluate audiological characteristics in rheumatoid arthritis (RA) patients compared with controls using extended high frequency audiometry and analyze their correlations with RA activity and severity to identify patients at higher risk of hearing loss.Patients and methodsThe study was carried out on 95 RA patients and 100 controls. Every subject underwent pure tone audiometry (PTA) from 250 through 8000 Hz, speech audiometry and extended high frequency audiometry (EHFA) from 10,000 to 20000 Hz. Disease activity score (DAS28) and RA medical records-based index of severity (RARBIS) were assessed.ResultsPatients were 85 females and 10 males with age mean 46.5 ± 1.1 years and disease duration of 9.57 ± 0.61 years. The hearing thresholds (HT) of patients were significantly higher than those of controls at all PTA (p < 0.001) and EHFA frequencies (p < 0.001). Hearing loss (HL) was detected in 68.4% and 64.2% by using PTA, while EHFA revealed it in 100% and 97.9% of right and left ears of RA patients respectively. Hearing loss was bilateral, symmetrical and sensorineural in all cases. HT of EHFA significantly correlated with age (r = 0.63, p < 0.001), age at onset (r = 0.51, p < 0.001), disease duration (r = 0.3, p = 0.03), DAS28 (r = 0.31, p = 0.01) and RARBIS (r = 0.21, p = 0.03).ConclusionBilateral symmetrical sensorineural hearing loss (SNHL) is significantly more frequent in RA patients compared to control. EHFA is valuable test to detect HL in patients with RA. Older age, longer disease duration, higher disease activity and severity are important factors for the development of HL in RA.     

Galectin-3 and interleukin-7 as potential serologic markers in rheumatoid arthritis patients

Aim of the workTo assess the level of serum galectin-3 and interleukin-7 (Il-7) in rheumatoid arthritis (RA) patients and to study their association with disease activity as well as other disease parameters.Patients and methodsSerum samples from 66 RA patients and 20 matched controls were tested for galectin-3 and IL-7 using enzyme-linked immunosorbent assay (ELISA). Disease activity was assessed using disease activity score (DAS28).ResultsThe mean age of the patients was 46.6 ± 12.02 years, mean disease duration was 7.5 ± 7.6 years and they were 61 females and 5 males. The mean DAS28 of the patients was 4.72 ± 1.77. Serum galectin-3 and IL-7 were higher in RA patients (7.7 ± 5.7 ng/ml and 9.03 ± 5.97 pg/ml) than the control (1.5 ± 0.8 ng/ml and 1.6 ± 1.1 pg/ml) (p < 0.001). Serum galectin-3 and IL-7 significantly correlated with age (r = 0.27, p = 0.03 and r = 25, p = 0.04), DAS28 (r = 0.64, p < 0.001 and r = 39, p = 0.001), as well as to each other (r = 0.48, p < 0.001). Serum galectin-3 significantly correlated with ESR (r = 0.29, p = 0.018) and significantly higher in those with fever (p = 0.017). At a cutoff of 2.94 ng/ml, serum galectin-3 showed 84.8% sensitivity and 100% specificity (p < 0.001) and at 2.71 pg/ml, serum IL7 showed a sensitivity of 92.4% and a specificity of 95% (p < 0.001) to diagnose RA.ConclusionSerum galectin-3 and IL-7 were higher in patients than in controls and were increased with high disease activity making them promising biomarkers for RA. Both of them showed high diagnostic power for RA. This may provide further understanding of RA pathogenesis and suggest new therapeutic interventions.     

Progressive preclinical interstitial lung disease in rheumatoid arthritis

BACKGROUND: Early detection and treatment for interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objective of this study was to identify asymptomatic lung disease and potential therapeutic targets in patients having RA and preclinical ILD (RA-ILD). METHODS: Sixty-four adults with RA and 10 adults with RA and pulmonary fibrosis (RAPF) were referred to the National Institutes of Health, Bethesda, Maryland, and underwent high-resolution computed tomography (HRCT) and pulmonary physiology testing. Proteins capable of modulating fibrosis were quantified in alveolar fluid. RESULTS: Twenty-one of 64 patients (33%) having RA without dyspnea or cough had preclinical ILD identified by HRCT. Compared with patients without lung disease, patients with RA-ILD had statistically significantly longer histories of cigarette smoking (P< .001), increased frequencies of crackles (P= .02), higher alveolar-arterial oxygen gradients (P= .004), and higher HRCT scores (P< .001). The HRCT abnormalities progressed in 12 of 21 patients (57%) with RA-ILD. The alveolar concentrations of platelet-derived growth factor-AB and platelet-derived growth factor-BB were statistically significantly higher in patients having RA-ILD (mean [SE], 497.3 [78.6] and 1473 [264] pg/mL, respectively) than in patients having RA without ILD (mean [SE], 24.9 [42.4] and 792.7 [195.0] pg/mL, respectively) (P< .001 and P=.047, respectively). The concentrations of interferon gamma and transforming growth factor beta(2) were statistically significantly lower in patients having RAPF (mean [SE], 5.59 [1.11] pg/mL and 0.94 [0.46] ng/mL, respectively) than in patients having RA without ILD (mean [SE], 14.1 [1.9] pg/mL and 2.30 [0.39] ng/mL, respectively) (P=.001 and P=.006, respectively) or with preclinical ILD (mean [SD], 11.4 [2.6] pg/mL and 3.63 [0.66] ng/mL, respectively) (P=.04 and P=.007, respectively). Compared with patients having stable RA-ILD, patients having progressive RA-ILD had statistically significantly higher frequencies of treatment using methotrexate and higher alveolar concentrations of interferon gamma and transforming growth factor beta(1) (P=.046, P=.04, and P=.04, respectively). CONCLUSIONS: Asymptomatic preclinical ILD, which is detectable by HRCT, may be prevalent and progressive among patients having RA. Cigarette smoking seems to be associated with preclinical ILD in patients having RA, and treatment using methotrexate may be a risk factor for progression of preclinical ILD. Quantification of alveolar proteins indicates that potential pathogenic mechanisms seem to differ in patients having RA-ILD and symptomatic RAPF.     

Effect of education on disease activity and functional status in rheumatoid arthritis patients

Aim of the workTo study the effect of education on rheumatoid disease in a cohort of Egyptian patients.Patients and methodsThis study included 1022 consecutive rheumatoid arthritis (RA) patients recruited from several rheumatology clinics of public and private sectors from Cairo, Kafr Elsheik and Fayoum governorates. Their mean age was 45.1 ± 12.4 years and mean disease duration was 85.9 ± 73 months. Patients were divided into groups according to their educational level (university degree/high school/illiterate) and were compared regarding their disease activity score (DAS28) and modified health assessment questionnaire (mHAQ) as a measure of the functional status.ResultsThe mean age of patients was 45.1 ± 12.4 years, they were 854 females and 168 males and disease duration of 85.9 ± 73 months. 106 (10.4%) were smokers and 333 (32.6%) were employed. 342 (33.5%) were illiterate, 455 (44.5%) were non-university-educated and 225 (22%) university educated. Educated patients showed significant lower disease activity (p = 0.001), swollen joint count (p = 0.044), tender joint count (p = 0.001), doctors global assessment (p = 0.001), erythrocyte sedimentation rate (p = 0.003) and visual analogue scale (p = 0.001). Educated patients had significantly received more biologic therapy (p = 0.001) and attended regular follow-up (p = 0.001). They showed better functional status with significantly lower MHAQ and had significant higher percentage of employment (p = 0.001). Rheumatoid patients with a university degree had significantly lower diseases activity and better functional indices compared to those without. Further regression analysis showed that university education is a predictor for low disease activity.ConclusionRheumatoid disease is influenced by education among Egyptians. Higher educated patients had lower disease activity and better functional outcome, and university education predicts low disease activity among Egyptian RA patients.     

Collagen triple-helix repeat containing 1 (CTHRC1) protein in rheumatoid arthritis patients: Relation to disease clinical,radiographic and ultrasound scores

Aim of the workto study the relationship between collagen triple helix repeat containing 1 (CTHRC1) protein serum levels and disease activity, patients’ well-being, as well as ultrasonographic and radiological scores in patients with rheumatoid arthritis (RA).Patients and methodsThe work included 70 RA patients and 70 age and gender matched controls. The disease activity score (DAS28) and health assessment questionnaire (HAQ) were assessed. Modified Larsen's score was used to score the hands and feet digital radiographs and musculoskeletal ultrasound (MSUS) examination using ultrasound-7 score was carried out. Serum CTHRC1 levels were measured by ELISA.ResultsPatients were 62 females and 8 males (F: M 7.8:1), their mean age was 42.2 ± 17.7 years and median disease duration 15 years. The median CTHRC1 serum levels were significantly higher in patients (453 ng/dl; 158–688 ng/dl) than control (99 ng/dl; 67–179 ng/dl) (p < 0.001). CTHRC1 was significantly increased in those with high activity (p < 0.001).CTHRC1 levels significantly correlated with DAS28 (r = 0.87,p < 0.001), CRP (r = 0.43,p < 0.001) and total ultrasound-7 score (r = 0.27,p = 0.03). Only total US7 score (p = 0.003) and CTHRC1 (p < 0.001) were significant predictors of activity. Serum CTHRC1 could significantly differentiate between patients and controls at cut off 179 ng/ml; sensitivity 95.7 % and specificity 100 % (p < 0.001) and between patients active and in remission at cut off 324 ng/ml; sensitivity 92.2 % and specificity 94.7 % (p < 0.001).ConclusionsPatients with RA have significantly elevated serum levels of CTHRC1. In the process of structural bone ultrasonographic abnormalities as well as disease activity in RA patients, elevated CTHRC1 levels play a key role.     

Serum irisin level in rheumatoid arthritis patients: Relationship to disease activity,subclinical atherosclerosis,and cardiovascular risk factors

Aim of the workTo assess serum irisin level in rheumatoid arthritis (RA) patients, determine the relationship between irisin levels, disease activity and cardiovascular (CV) risk factors, and to evaluate its performance in predicting subclinical atherosclerosis and disease activity.Patients and methods60 RA patients and 30 controls were recruited for serological enzyme linked immunosorbant assay (ELISA) testing of irisin levels. Disease activity score (DAS28), health assessment questionnaire disability index (HAD-DI) and American college of rheumatology classification of functional status were assessed. Levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), glycated hemoglobin (HbA1c), insulin and lipid profile were measured. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated. Carotid intimal medial thickness (C-IMT) was measured and echocardiography performed.ResultsSerum irisin levels were significantly lower in patients (9.8 ± 10.6 ng/ml) vs. controls (20.5 ± 13.8 ng; p < 0.001). Irisin levels inversely correlated significantly with C-IMT, body mass index (BMI), HOMA-IR, disease activity and disability. Patients with CV involvement showed significantly lower serum irisin level, increased disease activity and disability. Classifying patients based on cut-off values of DAS28 into low, moderate, and high disease activity, a significant difference in irisin levels was found, being lowest among highly active patients. Irisin performed as an excellent independent indicator of subclinical atherosclerosis (p < 0.001) and high disease activity (p < 0.001) in RA patients.ConclusionIn RA, decreased irisin were significantly associated with increased CV risk and performed better than traditional yardsticks in identifying disease activity. It may act as an independent indicator of subclinical atherosclerosis within RA patients.     

Collagen triple helix repeat containing 1 (CTHRC1) protein: A promising biomarker for evaluation of rheumatoid arthritis patients

Aim of the workTo assess serum collagen triple helix repeat containing 1 (CTHRC1) protein level in rheumatoid arthritis (RA) patients and compare it with healthy controls. In addition, to evaluate the relation of its level with RA activity and severityPatients and methodsThe study included 60 adult RA patients and 60 matched controls. Disease activity score (DAS28), modified health assessment questionnaire (MHAQ) and RA medical records-based index of severity (RARBIS) were assessed in RA patients. Serum CTHRC1 levels were measured in patients and controls by enzyme linked immunosorbent assay (ELISA)ResultsThey were 49 females and 11 males patients with a mean age of 43.6 ± 10.8 years and disease duration of 8.8 ± 0.9 years. The mean of DAS28 was 4.9 ± 2 (1.95–8.6). Serum CTHRC1 levels were significantly higher in patients than controls (1009.5 ± 79.4 vs. 470.7 ± 8.2 ng/ml, p < 0.001).The optimum cut-off value of CTHRC1 to discriminate patients from control was > 583.5 ng/ml with sensitivity of 98.3% and specificity of 100%. CTHRC1 significantly correlated with DAS28 (r = 0.81, p < 0.001), MHAQ (r = 0.14, p = 0.002), RARBIS (r = 0.41, p = 0.006), erythrocyte sedimentation rate (ESR) (r = 0.57, p < 0.001), C-reactive protein (CRP) (r = 0.41, p = 0.002), rheumatoid factor (RF) (r = 0.31, p = 0.037) and anti-cyclic citrullinated peptide (anti-CCP) (r = 0.27, p = 0.036). The significant predictors of increase CTHRC1 among patients were elevation in DAS28 (ß=287.6; p = 0.007, CI = 83.4–491.9) and MHAQ (ß=369.7; p = 0.042, CI = 14.5–724.9)ConclusionSerum CTHRC1 is a promising biomarker for evaluation of RA patients. It can be used as a marker for RA diagnosis and in monitoring the disease activity and severity.