A GITRL-mTORC1-GM-CSF positive loop promotes pathogenic Th17 response in exacerbating Primary Sjögren's Syndrome.

OBJECTIVES: Glucocorticoid-induced Tumor-Necrosis-Factor-Receptor Family-related Protein (GITR), with its ligand (GITRL), plays an important role in CD4+T-cell-mediated autoimmunity. This study aimed to investigate the underlying mechanisms of GITRL in primary Sjögren's Syndrome (pSS). METHODS: pSS patients and healthy controls were recruited. Serum GITRL and Th17-related cytokines were determinated. RNA-Sequencing was performed to decipher key signal pathways. Non Obese Diabetes (NOD) mice was adopted as experimental Sjögren models and recombinant adeno-associated virus (rAAV) transduction was conducted to verify the therapeutic potentials of targeting GITRL in vivo. RESULTS: Serum GITRL was significantly higher in pSS patients and showed a positive correlation with leukopenia, thrombocytopenia, autoantibodies, lung involvement and disease activity. Serum GITRL was correlated with Th17-related cytokines. GITRL promoted expansion of Th17 and Th17.1 cells. Expansion of granulocyte-macrophage-colony-stimulating-factor (GM-CSF+)CD4+T cells induced by GITRL could be inhibited by blockade of GITRL. Moreover, GM-CSF could stimulate GITRL expression on monocytes. RNA-Sequencing revealed mammalian target of rapamycin complexes 1 (mTORC1) might be the key modulator. The increased phosphorylation of S6 and STAT3 and expansion of Th17 and Th17.1 cells induced by GITRL were effectively inhibited by rapamycin, suggesting a GITRL/mTORC1/GM-CSF positive loop in pathogenic Th17 response in pSS. Administration of rAAV vector expressing shRNA targeting GITRL alleviated disease progression in NOD mice. CONCLUSIONS: Our results identified the pathogenic role of GITRL in exacerbating disease activity and promoting pathogenic Th17 response in pSS through a GITRL/mTORC1/GM-CSF positive loop. These findings suggest GITRL might be a promising therapeutic target in the treatment of pSS.

Clinical and immunological characteristics and prognosis of patients with autoantibody negative dermatomyositis: a case control study.

OBJECTIVES: Myositis-specific antibodies (MSAs) and myositis-associated antibodies (MAAs) are associated with distinctive dermatomyositis (DM) clinical phenotypes. The aim of this study is to explicate the clinical and immunological features of MSAs-negative DM patients. METHODS: A total of 515 individuals diagnosed with DM was screened from 2013 to 2022 and 220 DM patients were enrolled in this retrospective cohort. Clinical and laboratory data of these patients were analyzed. RESULTS: MSAs-negative DM patients were categorized into two groups: MAAs-negative (MSAs (-)/MAAs (-)) group and MAAs-positive (MSAs (-)/MAAs (+)) group. The percentage of Raynaud's phenomenon (P=0.026) was higher in the MSAs (-)/MAAs (+) DM patients than the MSAs-positive DM patients and MSAs (-)/MAAs (-) DM patients. The proportion of rapidly progressive interstitial lung disease (RP-ILD) in the MSAs-negative DM patients was lower than that in the MSAs-positive group. The MSAs (-)/MAAs (+) group had a higher proportion of organizing pneumonia and usual interstitial pneumonia (P=0.011), and elevated eosinophils in their bronchoalveolar lavage fluid (P=0.008). Counts of lymphocytes (P=0.001) and CD16+CD56+ natural killer (NK) cells (P=0.012) were higher in the MSAs-negative group. Additionally, the percentage of CD4+TNFα+ (P=0.040), CD4+IFNγ+ (P=0.037), and CD4+IL-2+ (P=0.018) cells among total CD4+ T cells were higher in the MSA-negative DM patients compared with the MSAs-positive DM patients. Besides, MSAs-negative patients demonstrated a more favorable prognosis than MSAs-positive patients. Multivariable regression analysis identified advanced onset age, higher level of carcinoembryonic antigen (CEA), and RP-ILD as risk factors for mortality in DM patients. CONCLUSIONS: Compared with MSAs-positive group, MSAs-negative DM patients suffered less from organ involvement compared with MSAs-positive group and tend to have better prognosis. Key Points MSAs-negative DM patients exhibited distinct characteristics in comparison with MSAs-positive DM patients:   • The MSAs (-)/MAAs (+) DM patients demonstrated a higher prevalence of organizing pneumonia (OP) and usual interstitial pneumonia (UIP), and elevated eosinophil counts in bronchoalveolar lavage fluid.   • CEA levels were lower in MSAs-negative patients compared with MSAs-positive patients.   • Elevated counts of lymphocytes and CD16+CD56+ NK cells were identified in the MSAs-negative patients. Additionally, proportions of CD4+TNFα+, CD4+IFNγ+, and CD4+IL-2+ cells among total CD4+ T cells were higher in the MSAs-negative DM patients compared with DM MSAs-positive DM patients.   • MSAs-negative DM patients had a more favorable prognosis than MSAs-positive DM patients. A multivariable regression analysis revealed the advanced onset age, high CEA levels, and RP-ILD were risk factors for mortality in DM patients.

Study of 43 SLE patients with autoimmune liver cirrhosis: emphasis on clinical features and differences from lupus without cirrhosis.

OBJECTIVE: To investigate the clinical characteristics of systemic lupus erythematosus accompanied by autoimmune liver cirrhosis (SLE-ALC) patients and differences from the non-cirrhosis group. METHODS: Forty-three patients with SLE-ALC were enrolled in this study from 2653 patients with SLE in Peking University People's Hospital. A descriptive case-control study was performed between SLE-ALC patients and the entry time-matched non-cirrhosis group. RESULTS: Among the 43 SLE-ALC patients, 41 (95.3%) were female. Eight patients (18.6%) were first found to have cirrhosis and then diagnosed with SLE. Eighteen patients (41.9%) had jaundice and 27 (62.8%) had esophageal and gastric varices. The age of SLE-ALC patients was 51.1 ± 17.2 years, which was significantly older than the non-cirrhosis group (P < 0.001). Lung involvement was more common as initial manifestations in SLE-ALC patients during the SLE course (P=0.027). Compared with the non-cirrhosis group, SLE-ALC patients had worse liver function. A significantly higher rate of hematological system involvement (anemia, leucopenia, and thrombocytopenia) and a higher level of immunoglobulins were observed in SLE-ALC patients (P<0.05). Moreover, SLE-ALC patients displayed a lower positive rate of anti-double-stranded DNA and anti-ribosomal P protein (P<0.05). The most common radiologic manifestations are ascitic fluid (72.1%) and splenomegaly (71.4%) in SLE-ALC patients. Six SLE-ALC patients underwent liver biopsy, and interface hepatitis was present in all patients. CONCLUSIONS: Cirrhosis is rare in SLE patients but is manifested as a unique pattern of clinical features characterized by late-onset age, lung involvement, high immunoglobulins, and impaired liver function.

Dynamics of T follicular helper cells in patients with rheumatic diseases and subsequent antibody responses in a three-dose immunization regimen of CoronaVac.

Given increased acceptance of the CoronaVac, there is an unmet need to assess the safety and immunogenic changes of CoronaVac in patients with rheumatic diseases (RD). Here we comprehensively analysed humoral and cellular responses in patient with RD after a three-dose immunization regimen of CoronaVac. RD patients with stable condition and/or low disease activity (n = 40) or healthy controls (n = 40) were assigned in a 1:1 ratio to receive CoronaVac (Sinovac). The prevalence of anti-receptor binding domain (RBD) antibodies and neutralizing antibodies was similar between healthy control (HC) and RD patients after the second and the third vaccination. However, the titers of anti-RBD IgG and neutralizing antibodies were significantly lower in RD patients compared to HCs (p < 0.05), which was associated with an impaired T follicular helper (Tfh) cell response. Among RD patients, those who generated an antibody response displayed a significantly higher Tfh cells compared to those who failed after the first and the second vaccination (p < 0.05). Interestingly, subjects with a negative serological response displayed a similar Tfh memory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-derived peptides as their anti-RBD IgG positive counterpart, and all (4/4) of the non-responders in HCs, and 62.5% (5/8) of the non-responders in patients with RD displayed a positive serological response following the third dose. No serious adverse events were observed. In conclusion, our findings support SARS-CoV-2 vaccination in patients with RD with stable and/or low disease activity. The impaired ability in generating vaccine-specific antibodies in patients with RD was associated with a reduction in Tfh cells induction. The window of vaccination times still needs to be explored in future studies. Clinical trial registration: This trial was registered with ChiCTR2100049138.

Low dose versus standard dose rituximab for the treatment of antiphospholipid syndrome: A pilot study from a tertiary medical center.

Background: To investigate the therapeutic effects and safety of low-dose and standard-dose rituximab (RTX) in the treatment of antiphospholipid syndrome (APS). Methods: In this real-world study, we included 22 consecutive patients with APS who received RTX. Standard dose (SD) was defined as an overall dosage of RTX ≥ 1000mg in the induction period, and low dose (LD) was defined as an overall dosage of RTX <1000mg. Results: Of included patients, 1 patients died, 2 patients withdrew and 19 patients completed 6-month follow-up. Nine patients received SD-RTX and 13 patients received LD-RTX, and elder patients [LD-RTX vs. SD-RTX: (49.1 ± 15.5) vs. (35.8 ± 12.3) years, p = 0.044] and patients with later-onset [LD-RTX vs. SD-RTX: (46.8 ± 16.3) vs. (31.3 ± 13.6) years, p = 0.029] were more frequently included in LD-RTX than SD-RTX. Following 6 month RTX treatment, 8 patients (42.1%) achieved complete remission, 8 patients (42.1%) achieved partial remission and 3 patients (15.8%) showed no remission. The titers of anticardiolipin antibodies [baseline vs. 6 months: 30.8 (10.7, 90) vs. 19.5 (2.45, 69.10) U/L, p = 0.023] and the levels of erythrocyte sedimentation rate [baseline vs. 6 months: 29 (6, 63) vs. '6 (3, 14) mm/h, p = 0.021] exhibited a significantly decrease in all APS patients. Remission rate and titers of anti-ß2-glycoprotein I and lupus anticoagulant did not differ significantly between two groups. Conclusion: RTX might be a safe and effective option for patients with APS, and low dose confers equal efficacy as standard dose. Further cohort studies are needed to confirm our findings.

Risk Factors and Outcomes of Acute Myocardial Infarction in a Cohort of Antiphospholipid Syndrome.

Background: Antiphospholipid syndrome (APS) is a disorder associated with thromboembolic diseases, including acute myocardial infarction (AMI). Given that AMI is a relatively common condition with poor prognostic features, identification of risk factors for AMI in APS is important. Methods: A retrospective cohort study was performed consisting of 332 patients with APS, and 239 patients with thrombotic APS were finally included. Patients were followed up in the outpatient department for 5 years. Clinical data and laboratory parameters were analyzed to identify the risk factors for AMI in APS. The primary and secondary clinical outcomes were all-cause mortality and recurrence of thrombosis, respectively. Results: AMI was observed in 12.1% (29/239) of patients with APS. Compared to patients without AMI, patients with AMI had multiple organ thrombosis (55.1 vs. 34.3%, p = 0.029), recurrent thrombosis (58.6 vs. 34.3%, p = 0.011), a higher incidence of atherosclerosis (62.1 vs. 23.8%, p < 0.001), higher neutrophil count (×109/L) [4.68 (3.25, 8.17) vs. 3.71 (2.64, 5.80), p = 0.036], longer QT interval (ms) [438 ms (423, 454) vs. 425 ms (410, 446), p = 0.016], and fewer venous thrombosis events (27.6 vs. 63.3%, p < 0.001). Multivariate logistic regression analysis (adjusted for age and gender) identified several factors that were positively associated with AMI, including multiple organ thrombosis [odds ratio (OR) 8.862, 95% confidence interval (CI): 1.817-43.212, p = 0.007), atherosclerosis (OR 5.397, 95%CI: 1.943-14.994, p = 0.001), and elevated neutrophil count (>6.3 ×109/L) (OR 3.271, 95%CI: 1.268-8.440, p = 0.014). The venous thrombosis was negatively associated with AMI (OR 0.106, 95%CI: 0.036-0.314, p < 0.001). Kaplan-Meier analysis revealed that the recurrence rates of arterial thrombosis differed significantly between patients with AMI and those without AMI [hazard ratio (HR) = 3.307, p = 0.038]. Conclusion: Atherosclerosis, multiple organ thrombosis, an increased number of neutrophils are variables positively associated with AMI in APS, and venous thrombosis had a negative association with AMI. AMI only predicts the subsequent recurrence of arterial thrombosis. These findings suggest that distinct pathophysiological mechanisms may exist and contribute to the development of venous or arterial thrombotic APS.

Low Dose Interleukin-2 Ameliorates Sjögren's Syndrome in a Murine Model.

Sjögren's syndrome (SS) is a systemic autoimmune disease with no efficient treatment, and it is associated with dysregulated immune cells and impaired interleukin (IL)-2 signaling. IL-2 is critical for the development and maintenance of Treg cells. The use of low dose of IL-2 (LDIL-2) in the treatment of autoimmune diseases is promising, but the efficacy and mechanism in SS therapy are still to be confirmed. This study aims to investigate the therapeutic effect of LDIL-2 on SS in NOD (non-obese diabetic) mice. NOD mice (female, 8 weeks old) were randomly assigned into three groups (n = 8). Low dose of IL-2 (LDIL-2), high dose of IL-2 (HDIL-2), and isometric sterile water (control) were administered subcutaneously daily from week 8 to week 16. LDIL-2 administration significantly recovered the reduction in saliva flow and suppressed lymphocyte inflammation of the submandibular glands (SMGs) when compared with those treated with sterile water as controls (p < 0.05). SS related biomarkers including ANA, Anti-SSA/Ro, and Anti-SSB/La also declined (p < 0.05). In the low dose of IL-2 treated group, the proportion of CD4+CD25+Foxp3+Tregs in both spleen and cervical-lymph-node were higher than control mice (p < 0.05). Furthermore, CD4+Bcl-6+PD-1+CXCR5+Tfh cells, CD4+IFN-γ+Th1 cells, and CD4+IL-17A+Th17 cells were significantly reduced in LDIL-2 group (p < 0.05). Analysis of the SMGs biopsies showed significantly decreased inflammation scores after LDIL-2 administration and an increase of Tregs with immunohistochemical staining. Our findings provide in vivo evidence that LDIL-2 was an effective therapeutic intervention for SS observed in NOD mice and may restore immune balance through the promotion of Treg and suppression of germinal center (GC) B cells and effector T cells.

Intestinal butyrate-metabolizing species contribute to autoantibody production and bone erosion in rheumatoid arthritis.

The imbalance between pathogenic and beneficial species of the intestinal microbiome and metabolism in rheumatoid arthritis (RA) remains unclarified. Here, using shotgun-based metagenome sequencing for a treatment-naïve patient cohort and a "quasi-paired cohort" method, we observed a deficiency of butyrate-producing species and an overwhelming number of butyrate consumers in RA patients. These outcomes mainly occurred in patients with positive ACPA, with a mean AUC of 0.94. This panel was also validated in established RA with an AUC of 0.986 in those with joint deformity. In addition, we showed that butyrate promoted Tregs, while suppressing Tconvs and osteoclasts, due to potentiation of the reduction in HDAC expression and down-regulation of proinflammatory cytokine genes. Dietary butyrate supplementation conferred anti-inflammatory benefits in a mouse model by rebalancing TFH cells and Tregs, as well as reducing antibody production. These findings reveal the critical role of butyrate-metabolizing species and suggest the potential of butyrate-based therapies for RA patients.

bFGF could be a biomarker of malignancy in RS3PE syndrome: an ambispective single-center cohort analysis of 51 patients.

OBJECTIVES: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare inflammatory arthritis, with a higher incidence of malignancy. The aim of this study is to identify biomarkers for predicting malignancy in RS3PE. METHODS: A total of 51 patients with RS3PE from September 2007 to May 2019 were retrospectively reviewed and followed for up to 5 years, with 15 patients with osteoarthritis (OA) and 14 patients with elderly-onset rheumatoid arthritis (EORA) as disease controls. Serum levels of angiogenesis cytokines were measured by electrochemiluminescent immunoassay and Luminex Human Magnetic Assay. Clinical data and laboratory parameters were analyzed to identify risk factors for malignancy. RESULTS: A total of forty-eight RS3PE patients (94.1%) were available with follow-up data; 8 patients (16.7%) were diagnosed with malignancy, of which 6 patients were hematological tumor; and 2 patients were solid tumors. Serum levels of basic fibroblast growth factor (bFGF) were exclusively higher in RS3PE patients with malignancy [14.21 (7.52, 23.18) ng/mL] than RS3PE patients without malignancy [4.32 (2.88, 7.42) ng/mL], OA [3.20 (2.20, 5.30) ng/mL], and EORA [3.20 (2.20, 5.30) ng/mL]. The optimal cut-off value of bFGF for malignancy was 10ng/mL in RS3PE. Logistic regression analysis indicated that elevation of bFGF was a risk factor for malignancy in RS3PE. CONCLUSIONS: This study indicated that bFGF was elevated in RS3PE patients with malignancy and could serve as a biomarker for predicting paraneoplastic RS3PE.

Elevated serum Dickkopf-1 is a biomarker for bone erosion in patients with psoriatic arthritis.

BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory arthropathy characterized by psoriasis and bone erosion on radiology. Dickkopf-1 (Dkk-1) is considered to be the main inhibitor of the Wnt signaling pathway and results in reduced osteoblast proliferation. The aim of this study was to investigate the serum level of Dkk-1 and its association with bone erosion in PsA patients. METHODS: Serum Dkk-1 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 69 patients with PsA and 60 controls, including 39 rheumatoid arthritis (RA) patients, and 21 healthy controls (HCs). Rheumatoid factor and anti-cyclic citrullinated peptide levels were also determined by ELISA. The association of Dkk-1 level with clinical and laboratory features of PsA was analyzed. Logistic regression analysis was used to analyze the risk factors for bone erosion in PsA. RESULTS: Dkk-1 was elevated in 68.1% (47/69) of the patients with PsA, 46.2% (18/39) of RA patients, and 9.5% (2/21) of HCs. Serum Dkk-1 concentration was significantly higher in PsA patients compared with that in HCs. The level of serum Dkk-1 was correlated with a swollen joint count, and levels of complement components 3 and 4. Elevated Dkk-1 level (odds ratio = 4.440, 95% confidence interval: 1.246-15.817, P = 0.021) was identified as the risk factor for bone erosion in PsA. CONCLUSIONS: The serum level of Dkk-1 is abnormally elevated in PsA patients. The elevation of Dkk-1 might be involved in the mechanism of bone erosion in patients with PsA.

Red meat intake is associated with early onset of rheumatoid arthritis: a cross-sectional study.

Accumulating evidence has implicated dietary factors as important risks for rheumatoid arthritis (RA) development, but analyses of the effects of red meat consumption on RA have yielded diverging results. The aim of this study was to explore the association between red meat and RA in a large-scale, cross-sectional study. From June to December 2016, a total of 733 patients were investigated, from which 707 participants were included in the analysis. These patients were divided into two groups according to their consumption of red meat (< 100 g/day; ≥ 100 g/day). The intake of red meat was assessed via physician-administered questionnaire. Generalized linear models were used to analyze relationships between the red meat intake and RA, adjusting for potential confounders including demographic, clinical, laboratory, and other dietary factors. Compared with low-intake red meat RA patients, high-intake red meat patients had an earlier onset age (p = 0.02) and had higher BMI (p = 0.003). The age at disease onset for the high-intake patients was 6.46 years earlier than for low-intake patients, after adjustment for demographic and other possible confounders (ß = - 6.46, 95% CI - 9.77, - 3.15; p = 0.0001). Further, stratified analyses showed that this inverse association of red meat intake with RA onset age was especially evident in smokers and overweight patients (BMI ≥ 24 kg/m2). In conclusion, high-intake red meat is associated with early onset of RA, especially in smokers or overweight patients. The findings indicate that eating less red meat could be a recommendation given to patients at risk for RA development.

Interleukin 17E associates with haematologic involvement and autoantibody production in primary Sjögren's syndrome.

OBJECTIVES: Primary Sjögren's syndrome (pSS) is one of the most prevalent systemic autoimmune diseases characterised by inflammation and tissue damage of exocrine glands, especially salivary or lacrimal gland. IL-17 related immune response is pathogenic with proinflammatory feature in pSS. However, whether IL-17E, an IL-17 family member, is involved in pSS pathogenesis or not, has not been determined. METHODS: Serum levels of IL-17E and IL-17A as comparison in 107 patients with pSS and 42 healthy controls were determined with multiplex cytokine assays. EULAR Sjögren's syndrome disease activity index (ESSDAI) score was calculated. Laboratory parameters were measured by standard laboratory techniques. The inflammatory infiltration of minor labial gland biopsies was graded based on numbers of lymphocyte and quantified by Focus Score (FS). Expression of IL-17E and IL-17A in the biopsy was evaluated with immunohistochemistry. RESULTS: Significantly elevated IL-17E in pSS patients associated with ESSDAI, haematologic disorders and autoantibody production, including anti-nuclear antibodies (ANA), rheumatoid factor (RF) and anti-SSA antibodies were found. Histopathological features showed that expression of IL-17E was found in labial salivary gland and correlated with lymphocytic infiltration. CONCLUSIONS: IL-17E expression in pSS patients was increased and associated with haematologic disorders, autoantibody production and lymphocytic infiltration in salivary gland. This finding indicated that IL-17E is involved in pSS pathogenesis.

Risk factors for cancer-associated myositis: A large-scale multicenter cohort study.

AIM: The aim of this study was to identify the risk factors and prognosis of patients with cancer-associated myositis (CAM). METHOD: Four hundred and eighty-seven patients with dermatomyositis (DM), clinical amyopathic dermatomyositis (CADM) and polymyositis (PM) from 3 clinical centers were enrolled retrospectively in this study. Clinical and laboratory data of CAM and non-CAM patients were compared. Logistic regression analysis was used to identify risk factors of CAM. RESULTS: Out of the 487 patients with DM/CADM/PM, 7.0% (34/487) of patients were classified as CAM. Older age (53.91 ± 13.32 vs. 48.76 ± 14.34 years), heliotrope rash (61.8% vs. 41.9%), shawl sign (41.2% vs. 22.1%), V sign (58.8% vs. 38.6%) were observed significantly more commonly in patients with CAM than those without CAM (all P < .05). Fever (17.7% vs. 37.8%), arthralgia/arthritis (23.5% vs. 45.7%), interstitial lung disease (ILD, 38.2% vs 68.9%) were significantly less common in the CAM group than the non-CAM group. Age at onset (odds ratio [OR] 1.036, 95% CI 1.001-1.072, P = .042), shawl sign (OR 2.748, 95% CI 1.107-6.822, P = .029), anti-transition initiation factor (TIF)-1γ antibody (OR 4.012, 95% CI 1.268-12.687, P = .018) were identified as the initial risk factors for the onset of CAM, and ILD was identified as a protective factor for CAM (OR 0.292, 95% CI 0.115-0.739, P = .009). All-cause mortality was significantly higher in CAM patients compared with non-CAM patients (P = .001). CONCLUSION: The mortality of patients with CAM was higher than DM/CADM/PM patients without cancer. Malignancy should be screened in DM/CADM/PM patients especially with risk factors, including older age, shawl sign, anti-TIF-1γ antibody, and lack of ILD.

Evaluation of soluble CD25 as a clinical and autoimmune biomarker in primary Sjögren's syndrome.

OBJECTIVES: Serum soluble CD25 (sCD25) is associated with T cell activation and regarded as a marker of disease activity in autoimmune disorders. The purpose of our study was to investigate the clinical relevance of sCD25 in patients with primary Sjögren's syndrome (pSS). METHODS: Sixty-five pSS patients and 60 healthy controls (HCs) with comparable age and gender were recruited. Serum samples were collected and sCD25 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory changes were examined after 12 weeks of treatment, and data were recorded in detail. The European League Against Rheumatism Sjögren's syndrome disease activity index (ESSDAI) was used to evaluate disease activity. RESULTS: Serum sCD25 levels were significantly increased in pSS patients, compared to HCs (p<0.001). The increased sCD25 were positively associated with ESSDAI scores (p=0.006), especially the haematological domain (p=0.002), and erythrocyte sedimentation rate, and levels of C-reactive protein, immunoglobulin G and γ-globulin (p<0.001, <0.001, 0.045 and 0.011, respectively). High sCD25 was strongly associated with anaemia (p=0.014) and was inversely correlated with haemoglobin levels (p=0.002). In further analysis, we found that patients with autoimmune haemolytic anaemia (AIHA) had the highest levels of sCD25, followed by patients with chronic disease of anaemia (ACD) and iron-deficiency anaemia (IDA). With the improvement after treatment, serum sCD25 levels were significantly decreased, accompanied by resolved anaemia compared to baseline (p=0.001). CONCLUSIONS: sCD25 was associated with disease severity, especially anaemia in patients with pSS and may serve as an indicator of disease activity.

Predictors and Mortality of Rapidly Progressive Interstitial Lung Disease in Patients With Idiopathic Inflammatory Myopathy: A Series of 474 Patients.

Objective: This study was conducted to identify the characteristics and prognosis of rapidly progressive interstitial lung disease (RP-ILD) in idiopathic inflammatory myopathy (IIM) and to assess the predictors for poor survival of RP-ILD in IIM. Methods: A total of 474 patients with IIM were enrolled retrospectively according to medical records from Peking University People's Hospital. Clinical and laboratory characteristics recorded at the diagnosis of patients with RP-ILD and chronic ILD (C-ILD) were compared. The Kaplan-Meier estimator and univariate and multivariate analyses were used for data analysis. Results: ILD was identified in 65% (308/474) of patients with IIM. Patients with ILD were classified into two groups based on lung features: RP-ILD (38%, 117/308) and C-ILD (62%, 191/308). RP-ILD resulted in significantly higher mortality in IIM compared with C-ILD (27.4 vs. 7.9%, P < 0.05). In this study, by comparing IIM patients with and without RP-ILD, a list of initial predictors for RP-ILD development were identified, which included older age at onset, decreased peripheral lymphocytes, skin involvement (periungual erythema, skin ulceration, and subcutaneous/mediastinal emphysema), presence of anti-MDA5 antibody, serum tumor markers, etc. Further multivariate Cox proportional hazards model analysis identified that anti-MDA5 positivity was an independent risk factor for mortality due to RP-ILD (P < 0.05), and lymphocytes <30% in BALF might also be associated with poor survival of myositis-associated RP-ILD (P < 0.05). Conclusion: Our study shows that RP-ILD results in increased mortality in IIM. Anti-MDA5 positivity and a lower lymphocyte ratio in BALF might be the predictive factor of mortality due to RP-ILD.

Effect of sustained intensive therapy with disease modifying anti-rheumatic drugs in rheumatoid arthritis: a 5-year real-world consecutive study.

BACKGROUND: Intensive therapy with disease modifying anti-rheumatic drugs (DMARDs) has been reported to improve the outcomes of rheumatoid arthritis (RA). However, real-world study on the effect of intensive therapy on RA sustained remission is still lacking. This study aimed to investigate the outcome of sustained intensive DMARD therapy (SUIT) for RA in a real-world 5-year consecutive cohort. METHODS: Based on a consecutive cohort of 610 out-patients with RA, remission of RA was assessed in 541 patients from 2012 to 2017, by dividing into SUIT, non-SUIT, and intermittent SUIT (Int-SUIT) groups. Changes in the disease activity scores were evaluated by 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR), 28-joint disease activity score based on C-reactive protein (DAS28-CRP), and clinical deep remission criteria (CliDR). Cumulative remission rates between different groups were compared using Kaplan-Meier curves and predictive factors of sustained remission were identified by univariate and multivariate logistic regression analysis. RESULTS: The remission rates of the SUIT group decreased from 12.0% (65/541) to 5.6% (20/359) based on DAS28-ESR, from 14.0% (76/541) to 7.2% (26/359) based on DAS28-CRP, and from 8.5% (46/541) to 3.1% (11/359) based on CliDR, respectively, with a gradually decreasing trend during the 5 years. The SUIT regimen led to a significantly higher cumulative remission rate than non-SUIT regimen based on DAS28-ESR (39.7% vs. 19.5%, P = 0.001), DAS28-CRP (42.0% vs. 19.6%, P = 0.001), and CliDR (24.5% vs. 8.7%, P = 0.001). The cumulative remission rates of patients treated with SUIT regimen were significantly higher than those treated with Int-SUIT regimen based on DAS28-ESR (39.7% vs. 25.7%, P = 0.043) and CliDR (24.5% vs. 14.2%, P = 0.047), but there was no significant difference between the two groups based on DAS28-CRP (42.0% vs. 27.4%, P = 0.066). Multivariate logistic regression analysis showed that the use of SUIT regimen was an independent favorable predictor according to different remission definitions (for DAS28-ESR: odds ratio [OR], 2.215, 95% confidence interval [CI]: 1.271-3.861, P = 0.005; for DAS28-CRP: OR, 1.520, 95% CI: 1.345-1.783, P = 0.002; for CliDR: OR, 1.525, 95% CI: 1.314-1.875, P = 0.013). CONCLUSION: Sustained intensive treatment of RA is an optimal strategy in daily practice and will lead to an increased remission rate.

Tea Consumption Is Associated with Decreased Disease Activity of Rheumatoid Arthritis in a Real-World, Large-Scale Study.

INTRODUCTION: The role of tea consumption on rheumatoid arthritis (RA) has been studied in recent years, but no clear conclusion has been drawn as a result of small sample size of the studies or the fact that only in vitro studies have been performed. OBJECTIVES: The aim of this study was to explore the possible association of tea consumption with RA through a large-scale, real-world study. METHODS: A total of 733 RA patients were investigated from June to December, 2016. The disease activity of RA was assessed according to disease activity score 28-erythrocyte sedimentation rate. The amount and types of tea consumption were recorded by on-site self-administered questionnaires. Logistic regression models were applied to analyze the correlation between tea consumption and disease activity, adjusting for demographics, clinical and laboratory factors. RESULTS: There was an inverse association between tea consumption and disease activity in RA patients (OR 0.66, 95% CI 0.46-0.94). Compared with non-tea drinkers, a higher-intake of tea (>750 mL/day) was associated with lower disease activity of RA (OR 0.39, 95% CI 0.19-0.79), but not low-intake (≤750 mL/day; OR 0.83, 95% CI 0.42-1.63). A significant dose-response association was found between the amount of tea consumption and disease activity (p for trend <0.01). Further hierarchical regression analysis showed that such inverse associations were mainly present in female patients (p = 0.004), non-smokers (p = 0.01) or elders (≥60 years; p = 0.01). CONCLUSION: Tea consumption is associated with decreased disease activity of RA, suggesting the potential beneficial effect of tea in the disease.

Risk factors of interstitial lung diseases in clinically amyopathic dermatomyositis.

BACKGROUND: Clinically amyopathic dermatomyositis (CADM) is a unique sub-type of idiopathic inflammatory myopathies with a high prevalence of interstitial lung disease (ILD). Poor prognosis of the patients was strongly associated with rapid progressive ILD. The aim of this study was to identify risk factors for prediction of different types of ILD in CADM. METHODS: In this study, data of 108 inpatients with CADM were collected, including 87 with ILD. The baseline clinical data and laboratory parameters, including myositis-specific and associated antibodies and tumor-associated antigens were analyzed to identify risk factors for acute or subacute interstitial pneumonitis (A/SIP) and chronic interstitial pneumonitis (CIP). RESULTS: In 87 patients with CADM-ILD, 39 (36.1%) were A/SIP, and 48 (44.4%) were CIP. There were 22 (20.4%) patients with asymptomatic ILD who were detected by routine high resolution computed tomography. Cytokeratin-19 fragment (CYFRA21-1) was significantly higher in CADM-ILD than that in CADM patients without ILD; carcinoembryonic antigen and neuron-specific enolase were significantly elevated in A/SIP than that in CIP. Patients with A/SIP had a higher positive rate of anti-melanoma differentiation-associated gene 5 (MDA5), while patients with CIP had a higher positive rate of anti PL-12 and anti-Ro-52. Logistic regression analysis indicated that elevation of CYFRA21-1 was a risk factor for ILD, higher titer of anti-MDA5 indicated increased likelihood for A/SIP, and higher titer of anti-Ro-52 was also clearly associated with CIP. CONCLUSIONS: This study indicated that the prevalence of ILD was high in CADM. Asymptomatic ILD has been previously underestimated. Anti-MDA5 was a risk factor for the presence of A/SIP, and CYFRA21-1 was a risk factor for ILD.

Clinical deep remission and related factors in a large cohort of patients with rheumatoid arthritis.

BACKGROUND: Clinical remission is the treatment target in rheumatoid arthritis (RA). This study aimed to investigate clinical remission and related factors in a large cohort of patients with RA. METHODS: This study composed of 342 patients with RA. Data were collected by face-to-face interview of 1049 patients with RA who visited the Department of Rheumatology of three teaching hospitals from September 2015 to May 2016. The patients with RA were clinically assessed by rheumatologists and a four-page questionnaire was completed on site. Subsequently, patients fulfilled remission criteria were further analyzed. The practicability of different definitions of remission of RA was rated by a panel of rheumatologists. Sustained intensive disease modifying anti-rheumatic drug (DMARD) treatment was defined as a combination treatment with two or more DMARDs for at least 6 months. RESULTS: In this cohort of 342 patients with RA, the proportions of patients achieving remission were 38.0%, 29.5%, 24.9%, 21.1%, 19.0%, 18.1%, and 17.0%, based on criteria of disease activity score in 28 joints (DAS28) using CRP (DAS28-CRP), DAS28 using ESR (DAS28-ESR), routine assessment of patient index data 3 (RAPID-3), Boolean, simplified disease activity index (SDAI), clinical disease activity index, and the newly described clinical deep remission (CliDR), respectively. Boolean and CliDR are the best in practicability scored by rheumatologists (7.5 and 8.0, respectively). Compared with the non-sustained intensive group, sustained intensive treatment with DMARDs yielded higher remission rates of 25.6%, 23.8%, and 21.3% in patients with RA based on Boolean (χ = 3.937, P = 0.047), SDAI (χ = 4.666, P = 0.031), and CliDR criteria (χ = 4.297, P = 0.038). The most commonly prescribed conventional synthesized DMARDs (csDMARDs) in patients with RA was leflunomide, followed by methotrexate, and hydroxychloroquine. Compared with the non-remission group, patients achieving remission had a longer median duration of DMARDs (45.0 [22.8-72.3] months, Z = -2.295, P = 0.022). CONCLUSIONS: The findings in this study indicated that clinical deep remission is achievable in patients with RA. Sustained intensive DMARD treatment is needed to achieve a better outcome in RA.