Objective To probe into the level and clinical significance of anti-carbamylated protein （CarP） antibody in serologically negative patients with rheumatoid arthritis （RA）. Methods A total of 301 RA patients and 55 healthy controls were recruited. Demographic characteristics and clinical data including serum levels of rheumatoid factor （RF） and anti-cyclic citrullinated peptide （CCP） antibody were collected. Serum levels of IgG anti-CarP antibody were determined by ELISA. Results According to the 95th percentile of the anti-CarP antibody level in 55 healthy controls, the ceiling of normal value was ≤31 U/mL. Among 301 RA patients, the positive rates of RF, anti-CCP antibody and anti-CarP antibody were 74.8% （225/301）, 75.1% （226/301） and 15.9% （48/301）, respectively. The positive rates of anti-CarP antibody were 19.7% （15/76） in RA patients with negative RF and 20.0% （15/75） in RA patients with negative anti-CCP antibody, respectively. In negative-RF RA patients, additional detection of anti-CCP antibody could reduce the percentage of serologically negative RA patients by 39.5% （30/76）. Additional detection of anti-CarP antibody could lower the percentage by 19.7% （15/76）. Additional detection of both anti-CCP antibody and anti-CarP antibody could decrease the percentage by 50.0% （38/76）. In serologically negative RA patients （negative for both RF and anti-CCP antibodies）, additional detection of anti-CarP antibody could lower the percentage of serologically negative RA patients by 17.4% （8/46）. Conclusion Additional detection of anti-CarP antibody has supplementary value for the diagnosis of serologically negative RA which is currently a difficult issue in clinical practice.

Objective:To investigate the prevalence of hypertension and its associated factors in rheumatoid arthritis (RA) patients.Methods:Consecutive Chinese patients with RA were recruited from August 2015 to September 2019 at Department of Rheumatology, Sun Yat-sen Memorial Hospital. Demo-graphic data and clinical data were collected including indicators of disease activity, functional assessment and radiographic assessment, comorbidities and previous medications. Logistic regression analysis was used to evaluate the related factors of hypertension in RA patients.Results:There were 674 RA patients recruited with 82.3%(555/674) female and mean age (50±13) years. The prevalence rate of hypertension was 32.9% (222/674), followed by dyslipidemia (9.9%, n=67), type 2 diabetes (8.8%, n=59), hyperuricemia (8.5%, n=43), fatty liver disease (8.0%, n=54), cardiovascular disease (6.2%, n=42) and chronic kidney disease (3.3%, n=22). Compared with those without hypertension, RA patients with hypertension had advanced age with longstanding disease duration, higher disease activity indicators, worse joint destruction, and higher proportions of comorbidities. Multivariate logistic regression analysis showed that comorbidities including hyperuricemia [ OR=1.977, 95% CI(1.002, 3.900)], dyslipidemia [ OR=1.903, 95% CI(1.102, 3.288)] and fatty liver disease [ OR=2.335, 95% CI(1.278, 4.265)] were risk factors of hypertension after adjustment for age and gender. Conclusion:Hyperten-sion is the most common comorbidity in RA patients which is associated with comor-bidities including hyperuricemia, dyslipidemia and fatty liver disease. Detection and management of hyperten-sion and other cardiovascular disease related comorbidities in RA patients should be emphasized.

Objectives This study aims to investigate if addition of fibroblast-stromal cell markers to a classification of synovial pathotypes improves their predictive value on clinical outcomes in rheumatoid arthritis (RA). Methods Active RA patients with a knee needle synovial biopsy at baseline and finished 1-year follow-up were recruited from a real-world prospective cohort. Positive staining for CD20, CD38, CD3, CD68, CD31, and CD90 were scored semiquantitatively (0-4). The primary outcome was radiographic progression defined as a minimum increase of 0.5 units of the modified total Sharp score from baseline to 1 year. Results Among 150 recruited RA patients, 123 (82%) had qualified synovial tissue. Higher scores of CD20+ B cells, sublining CD68+ macrophages, CD31+ endothelial cells, and CD90+ fibroblasts were associated with less decrease in disease activity and greater increase in radiographic progression. A new fibroblast-based classification of synovial pathotypes giving more priority to myeloid and stromal cells classified samples as myeloid-stromal (57.7%, 71/123), lymphoid (31.7%, 39/123), and paucicellular pathotypes (10.6%, 13/123). RA patients with myeloid-stromal pathotype showed the highest rate of radiographic progression (43.7% vs. 23.1% vs. 7.7%, p = 0.011), together with the lowest rate of Boolean remission at 3, 6, and 12 months. Baseline synovial myeloid-stromal pathotype independently predicted radiographic progression at 1 year (adjusted OR: 3.199, 95% confidence interval (95% CI): 1.278, 8.010). Similar results were obtained in a subgroup analysis of treatment-naive RA. Conclusions This novel fibroblast-based myeloid-stromal pathotype could predict radiographic progression at 1 year in active RA patients which may contribute to the shift of therapeutic decision in RA.

Objective: To investigate the value of baseline anti-mutated citrullinated vimentin (MCV) antibody for predicting one-year radiographic progression in patients with rheumatoid arthritis (RA). Methods: Consecutive RA patients were recruited from November 2014 to July 2018 at Department of Rheumatology, Sun Yat-sen Memorial Hospital, Clinical data were collected including disease activity score in 28 joints with four variables including C-reactive protein (CRP).Serum anti-MCV antibody at baseline was detected by enzyme-linked immunosorbent assay. X ray assessment of both hands/wrists was performed and assessed according to the Sharp/van der Heijde modified score (mTSS) at baseline and the 12th month. Univariate and multivariate logistic regression analyses were used to identify the risk factors for one-year radiographic progression. Results: Among 220 RA patients recruited, the positive rate of anti-MCV antibody at baseline was 77.7%. Compared with those with negative anti-MCV antibody, RA patients with positive anti-MCV antibody had higher disease activity score in 28 joints with four variables induding CRP [3.8 (2.4, 5.0) vs. 3.1 (2.1, 4.0), P=0.007], more physical dysfunction (21.6% vs. 8.2%, P=0.033) and higher radiographic indicators including mTSS [11 (2, 27) vs. 4 (1, 10), P=0.003], joint space narrowing [JSN, 4 (0, 14) vs. 2 (0, 6), P=0.024] and joint erosion[JE, 5 (1, 18)vs. 3 (0, 5), P=0.003]. After one-year follow-up, sixty-six RA patients (30.0%) developed radiographic progression, the percentage of whom was significantly higher in positive anti-MCV group than that in negative anti-MCV group (33.9% vs.16.3%, P=0.018). Multivariate logistic regression analysis suggested that positive anti-MCV antibody at baseline was an independent risk factor for one-year radiographic progression (OR=2.341, 95%CI 1.002-5.469). Conclusion: Positive anti-MCV antibody at baseline predicts one-year radiographic progression in RA patients. In the future, anti-MCV antibody can be used not only as a supplementary laboratory marker, but also in disease activity assessment and prognosis prediction for RA.

目的探讨抗突变型瓜氨酸波形蛋白（MCV）抗体在类风湿关节炎（RA）诊断中的应用。方法前瞻性纳入RA患者,分别采用散射比浊法检测血清RF、ELISA检测抗环瓜氨酸肽（CCP）抗体和抗MCV抗体。若抗体水平升高但不超过3倍正常上限定义为低滴度阳性,若超过3倍正常上限定义为高滴度阳性。结果共纳入148例RA患者,RF、抗CCP抗体和抗MCV抗体的阳性率分别为72.3%、74.3%和77.7%,高滴度阳性率分别为52.7%、54.7%和65.5%,其中抗MCV抗体高滴度阳性率明显高于RF和抗CCP抗体（均P ＜0.05）。41例RF阴性的RA患者中,抗MCV抗体阳性率为46.3%。24例RF和抗CCP抗体均阴性的RA患者中,抗MCV抗体阳性率为33.3%,其中低滴度阳性的患者占8.3%,高滴度阳性者占25.0%。22例RF或抗CCP抗体至少1个低滴度阳性且均无高滴度阳性的患者中,抗MCV抗体低滴度阳性和高滴度阳性的患者分别占9.1%和59.1%。结论抗MCV抗体对诊断RA尤其是血清学阴性的患者有一定的补充价值。

Background: Aging leads to loss of muscle mass causing functional limitation and reduced quality of life. Myopenia is a new universal term for the presence of clinically relevant muscle wasting. However, little is known about the prevalence of myopenia in elderly rheumatoid arthritis (RA) patients and its influence on RA pathogenesis and disease characteristics. We aimed to explore the characteristics of muscle mass and distribution and their clinical significance. Methods: Consecutive RA patients were recruited and clinical data including disease activity (DAS28-CRP), physical function (health assessment questionnaire disability index, HAQ-DI) and radiographic indicators (modified Sharp score) were collected. The muscle mass and distribution were assessed by bioelectric impedance analysis. Myopenia was defined as appendicular skeletal muscle mass index (ASMI) ≤7.0kg/m2 (men) and ≤5.7kg/m2 (women). Results: Among 643 RA patients recruited, there were 165 (25.7%) elderly patients (age≥60 years) with mean age 65.1±4.5 years. Compared with young patients (age<60 years), elderly RA patients had significantly higher DAS28-CRP (median 3.4 vs. 3.2), HAQ-DI (0.38 vs. 0.13) and modified total Sharp score (mTSS, 16 vs. 9), as well as higher proportion of myopenia (54.5% vs. 41.4%, all P<0.01). Elderly RA patients with myopenia (n=90, 14.0%) had significantly higher DAS28-CRP (3.6 vs. 3.0), HAQ-DI (0.50 vs. 0.12) and mTSS (21 vs. 7) than those in young RA patients without myopenia (n=280, 43.5%), and had higher mTSS (21 vs. 10) than those in elderly RA patients without myopenia (n=75, 11.7%, all P<0.0083). Multiple linear regression analysis after adjustment showed that both age (10 years as a unit, β=0.065~0.108) and ASMI (β= -0.369~ -0.220, all P<0.05) were correlated with DAS28-CRP, HAQ-DI and mTSS. Mediation analysis after adjustment showed that age had total and direct effects on DAS28-CRP, HAQ-DI or mTSS. ASMI partially mediated the associations between age and DAS28-CRP, HAQ-DI or mTSS (all P<0.05). Conclusion: Our data firstly reveal that half of elderly RA patients manifest myopenia which aggravates the whole disease including disease activity, physical dysfunction and joint destruction as a mediator of age. Myopenia, a neglected complication in elderly RA should be emphasized.

Background: Chronic inflammation in rheumatoid arthritis (RA) can induce reduced muscle mass (myopenia) and ectopic fat deposition probably showing normal body mass index (BMI). We aimed to investigate their body composition (BC) characteristics and clinical significance. Methods: BMI and BC were collected in consecutive RA patients and control subjects. Myopenia was defined by appendicular skeletal muscle mass index (ASMI) ⩽7.0 kg/m 2 in men and ⩽5.7 kg/m 2 in women. Overfat was defined by body fat percentage (BF%) as ⩾25% for men and ⩾35% for women. Results: There were 620 RA patients (57.6% with normal BMI) and 2537 control subjects (62.5% with normal BMI) recruited. After 1:1 age and sex matching with control subjects, RA patients with normal BMI ( n = 240) showed significantly higher prevalence of myopenia (43.3% versus 22.1%) and overfat (19.2% versus 7.1%) as well as myopenia overlapping overfat (17.1% versus 3.3%). In all RA patients with normal BMI ( n = 357), there were 18.2% patients with myopenia overlapping overfat who had the worst radiographic scores and highest rates of previous glucocorticoid treatment and hypertension. Compared with those without, normal BMI RA patients with previous glucocorticoid treatment (24.4% versus 10.3%) or hypertension (27.8% versus 13.6%) had a higher rate of myopenia overlapping overfat. Previous glucocorticoid treatment [odds ratio (OR) = 2.844, 95% confidence interval (CI) 1.441–5.614] and hypertension (OR = 2.452, 95% CI 1.283–4.685) were potential associated factors of myopenia overlapping overfat in RA patients with normal BMI. Conclusion: Myopenia overlapping overfat is an important extra-articular manifestation which should not be ignored in RA patients with normal BMI, especially with glucocorticoid treatment and hypertension.

BACKGROUND:Numerous cross-sectional studies have reported the associations between rheumatoid arthritis (RA) and reduced skeletal muscle. We firstly explored the dynamic change of skeletal muscle and its effect on RA clinical outcomes in a real-world prospective cohort. METHODS:Consecutive RA patients were treated according to the treat-to-target strategy and completed at least 1-year follow up. Clinical data and muscle index (assessed by bioelectric impedance analysis) were collected at baseline and visits at 3, 6, 9 and 12 months. Myopenia was defined by appendicular skeletal muscle mass index ⩽7.0 kg/m2 in men and ⩽5.7 kg/m2 in women. A 1-year radiographic progression as primary outcome was defined by a change in the total Sharp/van der Heijde modified score ⩾0.5 units. RESULTS:Among 348 recruited patients, 315 RA patients (mean age 47.9 years, 84.4% female) completed 1-year follow up. There were 143 (45.4%) RA patients showing myopenia at baseline. Compared with those without baseline myopenia, RA patients with baseline myopenia had higher rate of 1-year radiographic progression (43.4% versus 21.5%, all p < 0.05). Baseline myopenia was an independent risk factor for 1-year radiographic progression with adjusted odds ratio (AOR) of 2.5-fold, especially among RA patients in remission at baseline both defined by Disease Activity Score in 28 joints (DAS28) including C-reactive protein (DAS28-CRP) or erythrocyte sedimentation rate (DAS28-ESR) with AOR of 18.5~42.9-fold. Further analysis of six subtypes of dynamic skeletal muscle change showed that newly acquired myopenia at endpoint was associated with radiographic progression (AOR of 5.4-fold). CONCLUSIONS:Reduced skeletal muscle is an independent predicting factor for 1-year aggravated joint destruction, especially in remission RA. The importance of dynamic monitoring of skeletal muscle and muscle improvement therapy are worth exploration.

Background: Comprehensive disease control has been recommended by EULAR guidelines for rheumatoid arthritis (RA) which includes simultaneous achievement of stringent control of the signs and symptoms of inflammation, the absence of radiographic progression and normal physical function. Identifying those patients at high risk of disability at a sufficiently early stage of their disease course presents a major challenge. The associations of body mass index (BMI) and body composition (BC) with physical activity function in RA patients still obscure. Objectives: To investigate the characteristics of BC and BMI in RA patients and their association with physical activity function. Methods: Consecutive RA patients were recruited and clinical data including disease activity, function and radiographic assessment were collected. BC was assessed by bioelectric impedance analysis. Overfat was defined by body fat percentage (BF%) as ≥25% for men and ≥35% for women. Myopenia was defined by appendicular skeletal muscle mass index (ASMI) ≤7.0kg/m2 in men and ≤5.7kg/m2 in women. Subjects were categorized by BMI as underweight (BMI<18.5 kg/m2), normal weight (18.5 kg/m2≤BMI<24 kg/m2), overweight (24 kg/m2≤BMI<28 kg/m2) and obese (BMI≥28 kg/m2) according to Chinese criteria. Physical dysfunction was defined by HAQ-DI≥0.5. Results: There were 516 RA patients (mean age 49.8±12.9 years old with 83% women) recruited, and 37% with physical dysfunction. Compared with those with normal physical function, RA patients with physical dysfunction were older with longer disease duration, and had higher disease activity indicators including timing of morning stiffness, 28TJC, 28SJC, PtGA, PrGA, PainVAS, ESR, CRP, DAS28-CRP, SDAI and CDAI, as well as higher radiographic assessment including mTSS, JSN subscore and JE subscore (all P<0.05). As for BMI and BC, RA patients with physical dysfunction had higher BF% (mean 31.05% vs. 29.02%, P=0.007) and prevalence of overfat (44% vs. 27%, P<0.001), lower ASMI (mean 5.73 vs. 6.11, P<0.001) and higher prevalence of myopenia (55% vs. 38%, P<0.001) than those with normal physical function, while no difference in BMI between two groups. After adjustment confounding factors, multivariate logistic regression analysis showed overfat (OR=2.990, 95%CI: 1.695-5.274) and myopenia (OR=1.960, 95%CI: 1.191-3.225) were positively associated with physical dysfunction respectively. Further compared with patients with normal fat, patients with overfat had significantly higher rates of dysfunction of all eight physical activities including dressing, rising, eating, walking, hygiene, reaching, griping and activities respectively (all P<0.01), with the highest rate 57.5% in eating dysfunction and the lowest rate 38.6% in dressing dysfunction. Comparisons between patients with and without myopenia showed similar results with the highest rate 52.4% in eating dysfunction and the lowest rate 37.7% in rising dysfunction in those with myopenia. Conclusion: Overfat and myopenia are present in near half RA patients with physical dysfunction which are associated with dysfunction of all eight physical activities especially eating. Acknowledgement: This work was supported by National Natural Science Foundation of China (no. 81671612 and 81801606), Guangdong Natural Science Foundation (no. 2017A030313576, 2017A030310236 and 2018A030313541) and Guangdong Medical Scientific Research Foundation (no. A2017109) Disclosure of Interests: None declared