J.-D. Ma

Serum Matrix Metalloproteinase-3 as a Noninvasive Biomarker of Histological Synovitis for Diagnosis of Rheumatoid Arthritis

Objective. To explore the correlation between matrix metalloproteinase- (MMP-) 3 and histological synovitis in rheumatoid arthritis (RA). Methods. Serum MMP-3 of 62 patients with active RA was detected by ELISA. Serial synovial tissue sections from all RA patients, 13 osteoarthritis, and 10 orthopedic arthropathies patients were stained with hematoxylin and eosin and immunohistochemically for MMP-3, CD3, CD20, CD38, CD68, and CD15. Results. The percentage of lining MMP3+ cells was significantly higher in RA patients especially with high grade synovitis and it was significantly correlated with Krenns synovitis score (r = 0.574, P < 0.001) and sublining inflammatory cells. Multivariate stepwise linear regression analysis revealed that the association of the percentage of lining MMP3+ cells with activation of synovial stroma, sublining CD68+ macrophages, and CD15+ neutrophils was stronger than other histological indicators. The percentage of lining MMP3+ cells was significantly correlated with serum MMP-3 in RA (r = 0.656, P < 0.001). Serum MMP-3 was higher in RA patients with high grade synovitis than that of low grade synovitis and significantly correlated with synovitis score and activation of synovial stroma subscore (all P < 0.05). Conclusion. Serum MMP-3 may be an alternative noninvasive biomarker of histological synovitis and RA diagnosis.

Elevated Serum IgG4 Defines Specific Clinical Phenotype of Rheumatoid Arthritis

Objectives. To explore the correlation of serum IgG4 (sIgG4) with clinical manifestations or therapeutic response in rheumatoid arthritis (RA). Methods. Consecutive 136 RA patients were recruited and followed up at regular interval. SIgG4 was detected by immunonephelometry. Serial synovial tissue sections from 46 RA patients were stained immunohistochemically for IgG4. Results. Forty-six percent of 136 RA patients had elevated sIgG4. Patients with elevated sIgG4 had higher sIgG4/sIgG ratio, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and anticyclic citrullinated peptide antibodies than those with normal sIgG4 (all P < 0.05). Among 45 patients who received methotrexate and leflunomide therapy, 50% (9/18) of patients with elevated sIgG4 and 85% (23/27) of patients with normal sIgG4 reached therapeutic target (disease activity score of 28 joints < 3.2) at 6-month visit (χ 2 = 6.508, P = 0.011). IgG4-positive plasma cell count correlated positively with sIgG4, total synovitis score, and CD3-, CD20-, and CD38-positive cell counts (all P < 0.05). Conclusions. Our results showed that elevated sIgG4 in RA is common and disproportional to total IgG and RA with elevated sIgG4 may be a specific clinical phenotype with higher disease activity, higher level of autoantibodies, and poor response to methotrexate and leflunomide therapy.

Short-course tocilizumab increases risk of hepatitis B virus reactivation in patients with rheumatoid arthritis: a prospective clinical observation

To investigate the impact of short‐course tocilizumab (TCZ) on hepatitis B virus (HBV) reactivation in rheumatoid arthritis (RA) patients.

Magnetic Resonance Imaging of Bilateral Hands Is More Optimal Than MRI of Unilateral Hands for Rheumatoid Arthritis

Objective. To explore the advantages of magnetic resonance imaging (MRI) of bilateral hands in rheumatoid arthritis (RA). Methods. Consecutive patients with active RA were recruited for clinical assessments, radiographs, and MRI of bilateral hands. Bilateral hands were scanned simultaneously on 3.0 T whole-body MRI system and were scored on synovitis, osteitis, and bone erosion according to the RA MRI scoring (RAMRIS) system. Results. Among 120 patients included, wrist bones and metacarpophalangeal joint (MCPJ) 2 proximal showed bone erosion in early RA. The second to fifth metacarpal bases and the second to fourth MCPJ distal showed more bone erosion in mid-stage or late-stage RA. When MRI of dominant unilateral hand was analyzed, MRI synovitis and osteitis in 5% of wrists and 3 MRI features in 5–14% of MCPJ were misdiagnosed (McNemar test, all p < 0.05). There were 46% wrist synovitis, 29–52% MCPJ2–5 synovitis, 45% wrist osteitis, and 20%–34% MCPJ2–5 osteitis not detected by joint tenderness and/or swelling. When the clinically more severe hand was selected for MRI of unilateral hand according to physical examination, MRI synovitis in 5% of wrists and 3 MRI features in 7–15% of MCPJ were misdiagnosed (all p < 0.05). Scatter plots and linear regression analyses were used to illustrate RAMRIS between dominant or selected hand (Y values) and nondominant or nonselected hand (X values). All linear models were markedly different from a Y = X linear model, indicating the dominant or clinically more severe hand could not represent the contralateral hand to evaluate RAMRIS. Conclusion. MRI of bilateral hands is more optimal than MRI of the unilateral hand in RA.

Joint damage is amplified in rheumatoid arthritis patients with positive thyroid autoantibodies

Background Autoimmune thyroid disease (AITD), which is characterized by an increased presence of thyroid autoantibodies (TAbs), such as antibodies against thyroid peroxidase (TPOAbs) and antibodies against thyroglobulin (TgAbs), has been reported to be associated with rheumatoid arthritis (RA) because AITD and RA both involve autoimmunity. However, few data are available on the incidence of TAbs in Chinese RA patients, and studies on the association between TAbs and joint damage as well as synovitis in RA patients remain sparse. Here, we aimed to evaluate the incidence of TAbs in a consecutive Chinese RA cohort and to investigate whether the elevated presence of TAbs is associated with joint damage and synovitis in RA patients. Methods A total of 125 hospitalized RA patients were consecutively recruited. Clinical data and available synovial tissues were collected at baseline, and TAbs and thyroid function were detected by chemiluminescent immunoassay. Patients who tested positive for TPOAbs or TgAbs were classified as the TAbs-positive group, and patients who tested positive for neither TPOAbs nor TgAbs were recruited as the TAbs-negative group. Disease activity was assessed using DAS28-ESR (the disease activity score in 28 joints and including the erythrocyte sedimentation rate). X-ray assessment of the hand/wrist was performed according to the Sharp/van der Heijde-modified Sharp score (mTSS), and patients with an mTSS score >10 were defined as having radiographic joint damage (RJD). Serial tissue sections were stained immunohistochemically for CD3, CD15, CD20, CD34, CD38, and CD68, and synovitis were assessed according to Krenn’s synovitis score. Results A total of 44 (35%) patients were positive for either TPOAbs or TgAbs. Importantly, there was a significantly greater percentage of patients with RJD in the TAbs-positive group versus the TAbs-negative group (68% vs. 42%, p = 0.005). Compared with the TAbs-negative group, significantly more CD38-positive plasma cells infiltrated the TAbs-positive synovium, and a higher percentage of patients with high-grade synovitis were observed in the TAbs-positive group (5/8, 63% vs. 5/14, 36%). Moreover, RF positivity and disease activity indicators, including TJC28, DAS28-ESR, and CDAI, were significantly higher in the TAbs-positive group (all p < 0.05). Adjusted logistic regression analysis revealed that positive TAbs (OR 2.999, 95% CI [1.301–6.913]; p = 0.010) and disease duration (OR 1.013, 95% CI [1.006–1.019]; p < 0.001) were independently associated with RJD, and an odds ratio of 2.845 (95% CI [1.062–7.622]) was found for RJD in women with positive TAbs (n = 37) compared with those without TAbs (n = 59) (p = 0.038). Conclusion Our data showed that joint destruction was amplified in RA patients with an elevated presence of TAbs, which supports the importance and necessity of TAbs and thyroid function screening and monitoring in RA patient management in clinical practice.

Elevated uric acid levels in premenopausal female systemic lupus erythematosus patients: Association with potential or existing renal damage

Do premenopausal female systemic lupus erythematosus (SLE) patients have a low incidence of hyperuricaemia (HU) as healthy premenopausal females? As of yet, there have been few studies. This study aims to investigate the serum uric acid (UA) levels of premenopausal female SLE patients and the associated clinical risk factors. 107 premenopausal female SLE patients were divided into two groups: the high UA SLE group (n = 45) and the normal UA SLE group (n = 62). In total, 50 age-matched healthy premenopausal females served as the control group. Serum UA concentration, kidney damage index, lupus index, disease activity score of lupus and serum lipid index were collected and compared between the SLE subgroups. Binary logistic regression and multiple linear regression analyses were used to analyse the association of high UA levels with clinical features. The mean UA level of the SLE group was significantly higher than that of the control group (509.73 ± 150.28 μmol/L vs 296.78 ± 69.87 μmol/L, P < 0.001), as was the incidence of HU (42.06% vs 14.00%, P = 0.01). The UA levels of the high UA SLE group and the normal UA SLE group were 515.91 ± 120.64 μmol/L and 245.71 ± 63.18 μmol/L, respectively, which was statistically significant (P < 0.001). None of the patients with HU had current or previous gout attacks. The frequency of patients with renal manifestations in the high UA SLE group was significantly higher than that in the normal UA SLE group (χ2 = 26.278, P < 0.001). In the SLE group, the medications azathioprine and cyclosporine were not associated with HU (P = 0.689), as analysed by binary linear regression. Using multiple linear regression analysis, it was found that urinary blood (P = 0.048), creatinine (P = 0.016), triglycerides (P = 0.029), peripheral white blood cells (P = 0.007) and renal manifestation (P < 0.001) were associated with HU in the SLE group. Our results demonstrate that premenopausal SLE patients had higher levels of UA than healthy premenopausal females, which may be associated with potential or existing renal damage.

Deleterious role of hepatitis B virus infection in therapeutic response among patients with rheumatoid arthritis in a clinical practice setting: a case-control study

BackgroundPrevious studies have revealed that hepatitis B virus (HBV) infection may be associated with rheumatoid arthritis (RA), while there are no further clinical studies regarding the role of HBV infection in RA progression during disease-modifying anti-rheumatic drug (DMARD) therapy. Here, we aimed to explore the influence of HBV infection on radiographic and clinical outcomes among patients with RA in a clinical practice setting.MethodsThirty-two consecutive patients with RA (Disease Activity Score 28-joint assessment based on C-reactive protein (DAS28-CRP) ≥2.6) with chronic HBV infection (CHB) were retrospectively recruited as the CHB group and 128 age-matched, sex-matched, and disease activity-matched contemporary patients with RA without CHB were included in the non-CHB group. Clinical data were collected at baseline and visits at month 1, 3, 6, and 12. The therapeutic target was defined as DAS28-CRP <2.6 in all patients or <3.2 in patients with long disease duration (>24 months). The primary outcome was the percentage of patients with one-year radiographic progression (a change in modified total Sharp score ≥0.5).ResultsCompared with the non-CHB group, a significantly higher percentage of patients with one-year radiographic progression was observed in the CHB group (53% vs. 17%, p < 0.001), with smaller proportions of patients achieving therapeutic target at month 6 and month 12 (53% vs. 82% and 53% vs. 75%, both p < 0.05), remission at month 6 (DAS28-CRP <2.6, 50% vs. 72%, p = 0.039), and American College of Rheumatology (ACR)20/50 responses and good or moderate European League Against Rheumatism (EULAR) responses mainly at month 6 and 12 (all p < 0.05). Multivariate logistic regression analysis revealed that CHB status was significantly associated with one-year radiographic progression and failure to achieve therapeutic target within 6 months. HBV reactivation occurred in 34% of patients with CHB during one-year follow up, with two patients suffering hepatitis flare.ConclusionsHBV infection may play a deleterious role in radiographic and clinical outcomes in patients with RA, and HBV reactivation should be paid close attention during immunosuppressive therapy.

FRI0391 The relationship between oestrogen receptors and hyperuricemia in young female systemic lupus erythematosus patients

Background We have found that the incidence of hyperuricemia of young female systemic lupus erythematosus (SLE) patients was higher than that of healthy young women[1]. Why the high level of oestrogen didn’t show protection in uric acid (UA) level of fertile female SLE patients? There few few reports yet. Objectives To investigate the relationship between UA level and the levels of oestrogen, oestrogen receptors, antibodies to oestrogen receptors. Methods This was a cross-sectional study of 62 fertile female SLE patients that were divided into two groups including a high UA group (n=27) and a normal UA group (n=35). Serum UA levels, kidney index, SLE disease indicators and levels of oestrogen, oestrogen receptors, antibodies to oestrogen receptors were determined. Multiple linear regression analysis was applied to analyse the associations of UA levels with clinical features and levels of oestrogen, oestrogen receptors and antibodies to oestrogen receptors. Results 1. The mean ages of the two groups were (28.62±7.89) years and (28.82±8.28) years respectively, with on significantly different (t=0.096, p=0.924). There was no SLE patients manifested renal failure (CRE level higher than 120 μmol/l). All the SLE patients were at the onset of disease. 2. The mean UA levels of the high UA group and the normal UA group were (531.74±134.05) μmol/L and (238.86±61.32) μmol/L respectively, with significant difference (t=−11.48, p<0.001). 3. In the high UA group, the levels of CRE, LDL, cystatin, urine protein and were dramatically higher than those were found in the normal UA group (t=−3.617,–3.319, -2.782,–2.979, and p=0.001, 0.002, 0.007, 0.004, respectively), and oestrogen receptor β level were significantly lower than that of the normal group (t=2.138, p=0.037). The positive rate of urine blood of the high UA group were significantly higher than that of the normal UA subgroup (χ2=6.213, p=0.012). 4. Multiple linear regression analysis revealed there were significant relationships between UA level and CRE, oestrogen receptor β, and urine protein, urine blood.Abstract FRI0391 – Table 1 Independently-Associated Clinical Biomarkers with Serological UA levels in fertile SLE female patients Variable Unstandardized Coefficients Standardised Coefficients t P 95% CI B SEM CRE 1.145 0.462 0.263 2.478 0.016 0.223–2.068 oestrogen receptor β −2.758 0.933 0.239 2.299 0.033 3.132–44.38 urine protein 2.906 1.042 0.286 2.788 0.019 0.825–4.986 UBLD 56.426 28.058 0.216 2.011 0.048 0.422–112.43 Constant 177.283 42.179 4.203 0.001 93.09–216.47 Conclusions Hyperuricemia in young female SLE patients indicated the renal damage, and low level of oestrogen receptor β may contribute to hyperuricemia. Reference [1] Liu H.-J, Ma J.-D, Mo Y.-Q, et al. The study on the uric acid level of the fertile female systemic lupus erythematosus patients. Ann Rheum Dis, 2015;74(S2):1095–1096. Disclosure of Interest None declared

Patients with Coexistence of Circulating Hepatitis B Surface Antigen and Its Antibody May Have a Strong Predisposition to Virus Reactivation During Immunosuppressive Therapy: A Hypothesis

Hepatitis B virus (HBV) reactivation is a well-recognized complication in patients who undergo immunosuppressive drug therapy. Although the recommendation of antiviral prophylaxis made by the American Gastroenterological Association in 2015 focuses on the risk stratification of different immunosuppressive drugs, risk factors for HBV reactivation are also worth identifying in clinical practice. Recent studies have shown that the uncommon serological pattern of coexistent circulating HBV surface antigen (HBsAg) and its antibody (anti-HBs) was associated with double mutations (A1762T/G1764A) in the basal core promoter (BCP) region of the HBV genome, which is critical for HBV replication. Here, we depicted rheumatoid arthritis (RA) patients with coexistent HBsAg and anti-HBs in our medical center, who developed HBV reactivation during immunosuppressive drug therapy. DNA sequencing analysis of the HBV genome revealed triple mutations (A1762T, G1764A, and T1753V) in the BCP region, which could further enhance the ability of HBV replication. Hence, a novel hypothesis is advanced for the first time that patients with coexistent HBsAg and anti-HBs may have a strong predisposition to HBV reactivation due to specific BCP mutations. This hypothesis would, if correct, justify the concurrent detection of HBsAg and anti-HBs in HBV screening in patients with rheumatic diseases and quickly recognize patients with high risk of HBV reactivation. Further controlled studies are needed to confirm this hypothesis.

AB1020 High Prevalence of BF% Obesity in Chinese Patients with Rheumatoid Arthritis: A Cross-Sectional Study

Background There is about 14%–19% lipid of weight in normal people and most of the lipid stores in fat cells that can secrete adipokines to promote inflammation, which may exacerbate rheumatoid arthritis (RA) synovial inflammation, rise severity of clinical feature, disable functional capacity and reduce quality of life. A worldwide study in 15 countries (mainly in Europe and the United States) identified 18% of RA patients as obese defined by body mass index (BMI ≥30 kg/m2), while higher prevalence of 25% in a USA-based study and 31% in a UK–based study were reported. However, little is known about the prevalence of obesity in Chinese RA patients. Objectives To investigate the prevalence and character of obesity in Chinese RA patients. Methods Two hundred and forty–seven consecutive RA patients were assessed BMI, waist circumference (WC), waist–to–hip ratio (WHR) and waist–to–height ratio (WHtR). Clinical data including RA disease activity, physical function and complications were collected. Body fat percentage (BF%) was assessed by bioelectric impedance and obesity by BF% was defined as >25% for men and >30% for women. Results (1) According to Chinese criteria of BMI, there were 19% patients with overweight and 5% with obesity. According to BF%, there was 52% patients with obesity and female RA patients had significantly higher prevalence of obesity than male patients (55% vs 31%, P=0.006, Figure 1). (2) Weight, total fat mass and trunk–to–appendicular fat ratio (TAFR) were significantly higher in BF% obesity patients than normal ones (all P<0.05). The percentages of patients whose fat distributed mainly in trunk rather than appendicular extremities (TAFR >1) was also higher in BF% obesity patients than normal ones (83% vs 43%, P<0.001, Table 1). (3) According to WC, WHR and WHtR, there were 33%, 41% and 42% patients with central obesity respectively. The trunk-fat-to-weight percentage (TfW%) was significantly higher in central obesity patients (according to WC in Chinese criteria) than that in normal WC patients (female: 18.7% (16.6%–19.8%) vs 13.6% (11.0%–15.7%); male: 15.0% (12.4%–18.3%) vs 7.4% (3.8%–10.6%), both P<0.001). ROC curve analysis showed that the cut–off value of the TfW% for diagnosing central obesity was 11.8% in men with sensitivity 91.7% and specificity 87.5% and 16.3% in women with sensitivity 81.2% and specificity 83.1% (male: AUC=0.941, 95%CI: 0.868–1.0; female: AUC=0.865, 95%CI: 0.811–0.919, both P<0.001). There were 95 (38%) patients with central obesity according to the cut–off value of the TfW% (female 38% and male 39%, Figure 1). (4) Comparing with normal BF% patients, BF% obesity patients were older with higher disease activity indicators (ESR and CRP) and had more complications such as dyslipidemia and fat liver (all P<0.05, Table 1). Conclusions This cross–sectional study suggests that high prevalence of BF% obesity in Chinese RA patients especially in female patients which might be associated with disease activity. Acknowledgement This work was supported by National Natural Science Foundation of China (81471597), Specialized Research Fund for the Doctoral Program of Higher Education (20130171110075) and Guangdong Natural Science Foundation (2014A030313074). Disclosure of Interest None declared