Tacrolimus Personalized Therapy based on CYP3A5 Genotype in Chinese Patients with Idiopathic Inflammatory Myopathies.

OBJECTIVE: Idiopathic inflammatory myopathies (IIM) are a heterogeneous and life-threatening group of diseases, especially anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis (MDA5+ DM) is reportedly strongly associated with high mortality rate. Tacrolimus (TAC) provides an excellent therapeutic option, but the trough concentration (Cmin) -outcome relationship remains unexplored. This study was undertaken to identify optimal Cmin and individualized dose based on CYP3A5 genotype for IIM patients. METHODS: 134 IIM patients with 467 Cmin were enrolled. We examined the relationship between TAC Cmin and relapses. The receiver operating characteristic analysis was used to confirm the optimal Cmin. Analyses of factors influencing Cmin were conducted. The dose requirement based on CYP3A5 genotype was confirmed. RESULTS: TAC Cmin is strongly associated with relapses. The optimal cutoff values were 5.30, 5.85, 4.85 and 5.35 ng/ml for acute, subacute, chronic and all phase IIM patients (p = 0.001, 0.013, 0.002, and < 0.001, respectively), as well as 5.35, 5.85, 5.55 and 5.85 ng/ml for acute, subacute, chronic and all phase MDA5+ DM patients (p = 0.007, 0.001, 0.036, and < 0.001, respectively). CYP3A5 genotype was one of the significant factors influencing TAC Cmin. CYP3A5 expressers required 0.059 mg/kg/d to attain the target Cmin, while nonexpressers required 0.046 mg/kg/d (p = 0.019). CONCLUSION: TAC treatment may elicit favorable outcome in patients with IIM and MDA5+ DM when Cmin exceeded 5.35 and 5.85 ng/ml, which is crucial to lower relapse rate. The individualized dose based on the CYP3A5 genotype provides a reference for TAC personalized therapy in IIM.

Tofacitinib versus thalidomide for mucocutaneous lesions of systemic lupus erythematosus: A real-world CSTAR cohort study XXVII.

OBJECTIVE: Thalidomide is an effective medication for refractory mucocutaneous lesions of systemic lupus erythematosus (SLE) and can treat arthritis in some autoimmune diseases, but it has some adverse reactions. Recently, the effectiveness of tofacitinib in treating mucocutaneous lesions of SLE has been reported. We aimed to compare the efficacy and safety of tofacitinib with thalidomide in treating mucocutaneous and musculoskeletal lesions in patients with SLE. METHODS: This study was a real-world cohort study based on the Chinese SLE Treatment and Research group (CSTAR) registry. SLE patients who manifested mucocutaneous and/or musculoskeletal symptoms and were prescribed tofacitinib or thalidomide were included. We retrospectively conducted comparisons between the tofacitinib and thalidomide groups regarding clinical improvements, SLE disease activity, serological indicators, glucocorticoid doses, and adverse events at the 1, 3, and 6-months time points. RESULTS: At 3 and 6 months, the tofacitinib group exhibited a higher proportion of patients with improvement in mucocutaneous and musculoskeletal issues. Additionally, a greater percentage of patients in the tofacitinib group achieved remission or a low disease activity state (LLDAS) at these time points. No significant serological improvements were observed in either the tofacitinib or thalidomide groups. Fewer adverse events were observed in the tofacitinib group than in the thalidomide group. CONCLUSIONS: Tofacitinib might be superior to thalidomide in the improvement of mucocutaneous and musculoskeletal lesions in SLE, and had a good safety profile.

Clinical features of anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis with macrophage activation syndrome.

OBJECTIVES: This study aimed to describe the clinical features of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) who had macrophage activation syndrome (MAS). METHODS: We retrospectively examined 44 patients with anti-MDA5-positive DM and compared the clinical features between patients with MAS (n = 11) and those without (n=33). Patients without MAS were selected randomly in the same year as those with MAS at a ratio of 3:1. Among patients with MAS, we compared the features between non-survivors and survivors. We used Fisher's exact test, Student's t test, the Mann-Whitney U test and the log-rank test for statistical analysis. RESULTS: Patients complicated with MAS had a significantly higher incidence of infection, heliotrope sign, Gottron's papule, V-neck sign, and higher serum levels of ferritin, aspartate aminotransferase (AST), lactic dehydrogenase (LDH), and creatine kinase (CK) than those without MAS (p<0.05). Among the 11 patients with MAS, 4 (36.4%) died after intensive treatment. Deceased patients were older, given more combination therapy with tofacitinib (TOF) and had a higher incidence of rapid progressive interstitial lung disease, infection, heart failure and renal impairment than those who survived (p<0.05). CONCLUSIONS: Among anti-MDA5-positive DM, Infection, DM typical rashes, and higher serum levels of ferritin, AST, LDH, and CK were more common in patients complicated with MAS. The mortality of patients with MAS was high, particularly among patients who were older, given more combination therapy with TOF, and had RP-ILD, infection, heart failure and renal impairment.

Predictors of mortality for dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 and optimal treatment.

OBJECTIVES: To explore the risk factors of early death in dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 antibody (anti-MDA5-DM). To explore the optimal treatment regimen for patients with anti-MDA5-DM. METHODS: Patients with newly onset anti-MDA5-DM from June 2018 to October 2021 in our centre were retrospectively reviewed for 6 months. Patients were divided into five groups based on initial treatments. The major outcome was mortality in 6 months. Secondary outcomes included remission and severe infection. RESULTS: A total of 214 patients were included in the study. During 6 month follow-up, 63 patients (30.14%) died, 112 patients (53.59%) achieved remission, 52 patients (24.88%) experienced serious infection and 5 patients (2.34%) were lost. Independent risk factors of mortality in the first 6 months after diagnosis were as follows: age> 53 years, skin ulcer, peripheral blood lymphocyte count (LYMP)≤ 0.6×109/L, lactate dehydrogenase (LDH) > 500 U/L, C reactive protein (CRP) > 5mg/L, anti-Ro52 antibody and ground-glass opacity (GGO) score> 2. On the contrary, prophylactic use of the compound sulfamethoxazole (SMZ Co) was independent protective factor. The five-category treatment was not an independent influencing factor of early death, but subgroup analysis found that patients with rapidly progressive interstitial lung disease (RPILD) responded better to a triple combination of high-dose glucocorticoids (GC), calcineurin inhibitors (CNI) and cyclophosphamide (CYC) or a triple combibation of GC, CNI and tofacitinib (TOF). CONCLUSIONS: Advanced age, skin ulcer, lymphopenia, anti-Ro52 antibody and higher levels of LDH, CRP and GGO score increase the risk of early death for MDA5-DM, while prophylactic use of SMZ Co is protective. Aggressive therapy with combined immunosuppressants may improve the short-term prognosis of anti-MDA5-DM with RPILD.

Comparison of clinical characteristics between patients with axial spondyloarthritis with and without acute anterior uveitis: a multicentre study of the Chinese Spondyloarthritis Registry.

OBJECTIVES: This study explores the clinical characteristics associated with the occurrence of acute anterior uveitis (AAU) in patients with axial spondyloarthritis (axSpA) within a large, multicentre database. METHODS: This observational, cross-sectional study of patients with axSpA used data from the Chinese Spondyloarthritis Registry between August 1, 2018, and March 31, 2020. The demographic and clinical features of patients with and without AAU were compared. Univariate and multivariate analyses were performed to determine the association between variables and uveitis. RESULTS: A total of 4304 patients were included in this study. The prevalence of AAU in patients with axSpA was 10.59%. Multivariate logistic regression analysis revealed a positive correlation between AAU and age at diagnosis (odds ratio [OR], 1.026; p<0.001), disease duration (OR, 2.117; p<0.001), current or past Achilles tendinitis (OR, 1.692; p<0.001), current or past dactylitis (OR, 1.687; p=0.002), current or past psoriasis (OR, 3.932; p<0.001), presence of human leukocyte antigen-B27 (HLA-B27) (OR, 2.787; p<0.001), and a good response to non-steroidal anti-inflammatory drugs (NSAIDs) (OR, 1.343; p=0.027). CONCLUSIONS: AAU was the most common extra-articular manifestation in the Chinese Spondyloarthritis Registry. In Chinese patients with axSpA, older age at diagnosis, longer disease duration, presence of HLA-B27, current or past Achilles tendinitis, current or past dactylitis, current or past psoriasis, and a good response to NSAIDs were positively associated with AAU.

Alterations in the human oral microbiota in systemic lupus erythematosus.

BACKGROUND: Alterations in oral microbiota in patients with systemic lupus erythematosus (SLE) is less evaluated. The aim of this study was to compare the characteristics of the oral microbiome in SLE patients and healthy controls, and construct an SLE classifier based on the oral microbiota. METHODS: We sequenced tongue-coating samples of individuals in treatment-naïve SLE (n = 182) and matched healthy controls (n = 280). We characterized the oral microbiome and constructed a microbial classifier in the derivation cohort and validated the results in the validation cohorts. Furthermore, the oral microbiome of posttreatment SLE (n = 73) was characterized. RESULTS: The oral microbial diversity of SLE was increased, and the microbial community was different between SLE and healthy controls. The genera Prevotella and Veillonella were enriched, while Streptococcus and Porphyromonas were reduced in SLE. In addition, an increase was noted in 27 predicted microbial functions, while a decrease was noted in 34 other functions. Thirty-nine operational taxonomy units (OTUs) were identified to be related with seven clinical indicators. Two OTUs were identified to construct a classifier, which yielded area under the curve values of 0.9166 (95% CI 0.8848-0.9483, p < 0.0001), 0.8422 (95% CI 0.7687-0.9157, p < 0.0001), and 0.8406 (95% CI 0.7677-0.9135, p < 0.0001) in the derivation, validation, and cross-regional validation groups, respectively. Moreover, as disease activity increased, Abiotrophia and Lactobacillales increased, while Phyllobacterium and unclassified Micrococcusaceae decreased. Finally, nine OTUs were selected to construct a classifier distinguishing posttreatment SLE patients from healthy controls, which achieved a diagnostic efficacy of 0.9942 (95% CI 0.9884-1, p < 0.0001). CONCLUSIONS: Our study comprehensively characterizes the oral microbiome of SLE and shows the potential of the oral microbiota as a non-invasive diagnostic biomarker in SLE.

Compounded sulfamethoxazole improved the prognosis of dermatomyositis patients positive with anti-melanoma differentiation-associated gene 5.

OBJECTIVES: Mortality of dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 antibody (anti-MDA5-DM) is alarming, especially during the first several months. Infection is an important cause of early death. As there are no reports regarding the effect of prophylactic use of compounded sulfamethoxazole (coSMZ; each tablet contains 400 mg of sulfamethoxazole and 80 mg of trimethoprim) in anti-MDA5-DM patients, we conducted this study to evaluate the efficacy of coSMZ in reducing the incidence of Pneumocystis jirovecii pneumonia (PJP). METHODS: Consecutive patients with new-onset anti-MDA5-DM from June 2018 to October 2021 in our centre were retrospectively reviewed for >12 months. They were divided into two groups-coSMZ and non-coSMZ-based on the initial use of prophylactic coSMZ. Mortality and the incidence of severe infection within 12 months were compared between two groups. RESULTS: Compared with the non-coSMZ group (n = 93), the coSMZ group (n = 121) had lower mortality (18.8% vs 51.1%; P < 0.001) and a lower incidence of PJP (6.8% vs 15.2%; P = 0.040) and fatal infection (16.1% vs 3.3%; P = 0.001) during the first 12 months from diagnosis. After adjusting for age, gender, disease duration, peripheral blood lymphocyte count, anti-MDA5 antibody titres, ground-glass opacity scores and treatments, an inverse association was revealed between the prophylactic use of coSMZ and incidence of PJP [adjusted odds ratio 0.299 (95% CI 0.102-0.878), P = 0.028]. CONCLUSION: Prophylactic use of coSMZ is an effective and safe way to improve the prognosis of anti-MDA5-DM patients by preventing the incidence of PJP.

Clinical features and independent predictors of Behçet's disease associated with myelodysplastic syndrome.

OBJECTIVES: To investigate the correlation of Behçet's disease (BD) with myelodysplastic syndrome (MDS) and identify the predictive risk factors in Chinese patients. METHODS: A retrospective study of BD associated with MDS (BD-MDS) patients from the First Affiliated Hospital of Zhengzhou University was conducted. RESULTS: Among 15 BD-MDS patients, 10 were females and 5 males. While 13 (86.7%) patients had abnormal karyotype, 11 patients with trisomy 8. 10 (66.7%) had gastrointestinal (GI) involvement. Compared with 60 general BD patients without MDS, the BD-MDS patients were significantly older. In addition, fever and GI involvement were more common in BD-MDS patients, whereas these patients had lower levels of leukocyte count, haemoglobin, and platelet count (p<0.05). Logistic regression analysis showed that GI involvement, low haemoglobin, and high ESR level were independently associated with the development of MDS in BD patients. BD-MDS patients with GI involvement (IBD-MDS) were usually much older and have more fever than IBD patients without MDS, as well as lower leukocyte count, haemoglobin level, platelet count, and higher erythrocyte sedimentation rate (ESR) and C-reactive protein levels (p<0.05). By comparison with 60 primary MDS patients without BD, the BD-MDS patients had more abnormal karyotypes and more trisomy 8 (p<0.05), while the distribution of 2016 WHO subtypes of MDS and IPSS-R categories were similar. CONCLUSIONS: Our findings suggest that cytogenetic abnormalities, especially trisomy 8, may play a role in the association of GI involvement, BD, and MDS. GI involvement, low haemoglobin, and high ESR level were independent predictors for MDS development in BD patients.

Research on the purification enhancement of ecological ponds: Integrating water cycle optimization and plants layout.

The hydrodynamic conditions of ponds are generally poor, which seriously affects the long-term water quality guarantee. In this research, the numerical simulation method was used to establish an integrated model of hydrodynamics and water quality for the simulation of the plant purification effect in ponds. Based on the flushing time using the tracer method, the purification rate of plants was introduced to consider the purification effect of plants on water quality. In-situ monitoring was carried out at the Luxihe pond in Chengdu, and the model parameters such as the purification rate of typical plants were calibrated. The degradation coefficient of NH3-N in the non-vegetated area was 0.014 d-1 in August and 0.010 d-1 in November. In areas with vegetation, the purification rate of NH3-N was 0.10-0.20 g/(m2·d) in August and 0.06-0.12 g/(m2·d) in November. The comparison of the results in August and November showed that due to the higher temperature in August, the plant growth effect was better, and the degradation rate of pollutants and the purification rate of pollutants by plants were higher. The flushing time distribution of the proposed Baihedao pond under the conditions of terrain reconstruction, water replenishment, and plant layout was simulated, and the frequency distribution curve of flushing time was used to evaluate the results. Terrain reconstruction and water replenishment can significantly improve the water exchange capacity of ponds. The reasonable planting of plants can reduce the variability of the water exchange capacity. Based on this combined with the purification effect of plants on NH3-N, the layout plan of Canna, Cattails, and Thalia in ponds was proposed.

Intravenous immunoglobulin for interstitial lung diseases of anti-melanoma differentiation-associated gene 5-positive dermatomyositis.

OBJECTIVE: Rapidly progressive interstitial lung disease (RP-ILD) in DM patients positive for anti-melanoma differentiation-associated gene 5 (anti-MDA5) autoantibody (MDA5-DM) often have a poor prognosis, frequently fatal. As there is a scarcity of data regarding the effect of intravenous immunoglobulin (IVIG) on RP-ILD in MDA5-DM patients (MDA5-RPILD), we conducted this study to determine the efficacy of a IVIG add-on initial treatment. METHODS: Patients with newly-onset MDA5-RPILD from September 2018 to June 2020 were retrospectively reviewed for 6 months in the First Affiliated Hospital of Zhengzhou University. They were divided into two groups: IVIG and non-IVIG groups. The major measurement of treatment outcome was the difference in the mortality in 3-month and 6-month between two group patients. Other relevant indicators were also recorded, including the incidence of infection, the dosages of GCs, the remission rate and the variables in laboratory data. RESULTS: The IVIG group (n = 31) showed significantly lower 6-month mortality rate than the non-IVIG group (n = 17) (22.6% vs 52.9%; P =0.033). The IVIG group patients had a higher remission rate at 3 months (71.0% vs 41.2%; P =0.044). Gradual reduction was observed in the first 3 months with regard to the titre of anti-MDA5 autoantibody, the serum level of ferritin and the ground glass opacification GGO scores. CONCLUSION: IVIG adjunct therapy is a very effective first-line treatment for patients with MDA5-RPILD. IVIG may increase the survival and remission rate by lowering ferritin concentration, anti-MDA5 titre and GGO score.

Anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis exhibit three clinical phenotypes with different prognoses.

OBJECTIVES: We aimed to identify different subtypes of dermatomyositis (DM) patients positive with anti-melanoma differentiation-associated gene 5 antibody (DM-MDA5+) for customised treatments to improve the outcomes. METHODS: Among 96 DM-MDA5+ patients, subgroups with similar phenotypes were delineated using hierarchical clustering analysis of the clinico-biological characteristics. Classification and regression trees were used to build a classification model and survival analysis was used to evaluate the prognoses of subgroups. RESULTS: Three subgroups were identified among 96 DM-MDA5+ patients, and patients in different subgroups had highly heterogenic manifestations and outcomes. Cluster 1 patients were referred to as mild group of rheumatologic patterns with good prognosis. Cluster 2 patients were referred to as young typical DM group with good prognosis. Cluster 3 patients were referred to as elderly rapidly progressive interstitial lung disease (RPILD) group with poor prognosis. A predictive model to classify patients was established, and three critical factors were found, including age, serum ferritin and myalgia. CONCLUSIONS: DM-MDA5+ patients have a poor short-term prognosis. Three clinical phenotypes with different prognoses were identified in DM-MDA5+ patients.

Clinical characteristics, outcome and prognostic factors in critically ill patients with lupus nephritis.

OBJECTIVES: To describe the clinical characteristics and outcome of patients with lupus nephritis (LN) in intensive care unit (ICU), identify prognostic factors and construct a predictive model of in-ICU survival. METHODS: A total of 505 ICU admissions of lupus patients were screened and LN patients confirmed by renal biopsy were enrolled. Clinical characteristics and outcome of patients in ICU were collected. A logistic regression analysis was performed to identify independent prognostic factors and a nomogram was plotted to construct a predictive model. RESULTS: A total of 70 patients with LN were enrolled. The median age of the patients was 28.5 years, and the median course of LN was two months. Renal pathology classes indicated that 38 patients were class IV, 11 were class IV+V, and 10 were class III. The most common primary cause of ICU admission was infection in 40 patients, followed by LN in 11 patients. Forty-one patients died in ICU. The multivariate analyses revealed that lactic acid (OR 1.682 [2.130-17.944], p=0.001), gamma-glutamyl transpeptidase (OR 1.057 [1.009-1.107], p=0.020), APACHE II (OR 3.852 [1.176-12.618], p=0.026), vasopressor (OR 10.571 [1.615-69.199], p=0.014) and platelet count (OR 0.967 [0.941-0.993], p=0.013) were independently associated with ICU survival of critical LN patients. A predictive model was constructed and validated. CONCLUSIONS: This study is the first to elucidate the features and identify prognostic factors in critically ill patients with LN. These findings could help clinicians to early identify high-risk patients of mortality, which consequently may reduce the mortality of critically ill patients with LN.

Association between triglyceride-glucose index and nonalcoholic fatty liver disease in type 2 diabetes mellitus.

BACKGROUND: Lipid and glucose metabolism abnormalities are associated with nonalcoholic fatty liver disease (NAFLD). The triglyceride-glucose (TyG) index is a recently developed indicator that can identify individuals at risk for NAFLD. However, the applicability of the TyG index for identifying NAFLD in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to investigate the ability of the TyG index to identify individuals at risk for NAFLD in the T2DM population. METHODS: A total of 2280 participants with T2DM were recruited in this cross-sectional study. The TyG index was calculated, and NAFLD was diagnosed by ultrasonography. Binary logistic regression models were used to evaluate the association of the TyG index, glycemic parameters and lipid parameters with NAFLD. RESULTS: Logistic regression analysis showed that the TyG index was significantly associated with NAFLD in subjects with T2DM, the odds ratio (OR) were 3.27 (95% confidence interval [CI], 2.03-5.27; P < 0.001) for NAFLD in the highest TyG quartile after adjustment for known confounders. In stratified analysis, an elevated TyG index were more remarkably associated with NAFLD in younger patients (< 65 years; OR, 2.35; 95% CI, 1.83-3.02; P < 0.001), females (OR, 2.69; 95% CI, 1.67-4.32; P < 0.001), patients with BMI < 25 kg/m2 (OR, 2.80; 95% CI, 2.01-3.91; P < 0.0001), and with lower high-density lipoprotein cholesterol (< 1 mmol/L; OR, 2.76; 95% CI, 1.98-3.83; P < 0.001). CONCLUSION: The TyG index is significantly associated with NAFLD and shows superior ability for identify NAFLD risk compared with other lipid and glycemic parameters in T2DM.

Proteomic analyses of plasma-derived exosomes in immunoglobulin (Ig) G4-related disease and their potential roles in B cell differentiation and tissue damage.

OBJECTIVE: To investigate the proteomic profiles of plasma exosomes isolated from patients with immunoglobulin (Ig) G4-related disease (IgG4-RD) and to determine their potential roles in B cell differentiation and tissue damage. METHODS: One hundred untreated IgG4-RD patients and 135 sex- and age-matched healthy controls (HCs) were enrolled in this study. A combination of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tandem mass tag (TMT)-label quantitation was used for proteomic profiling. Differentially expressed proteins were validated by Western blot, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) analyses. B cell activation, apoptosis, differentiation and reactive oxygen species (ROS) production were analyzed by flow cytometry. We also analyzed the correlations between differentially expressed complement proteins and laboratory parameters. RESULTS: A total of 178 differentially expressed proteins were identified in plasma exosomes in IgG4-RD patients compared with HCs, and these proteins were enriched predominantly in the complement cascade pathway. Furthermore, reduced expression levels of complement components C3 and C5 in IgG4-RD were correlated with clinical parameters. Following stimulation with IgG4-RD plasma exosomes, the percentages of naïve B cells decreased, while those of memory B cells and plasmablasts increased; the levels of cytochrome c, somatic (CYCS) and downstream complement system activation also increased. Moreover, ROS production was greater in B cells of IgG4-RD patients than in those of HCs. In affected submandibular glands, the BCR signalling pathway was activated, and exosomes were enriched. CONCLUSION: Proteomic profiling revealed that plasma exosome proteins may participate in the pathogenesis of IgG4-RD through complement activation and may be involved in B cell differentiation and activation of the B cell auto-oxidative damage pathway.

Laboratory-confirmed bloodstream infection in systemic lupus erythematosus: Risk profiling and short-term mortality.

OBJECTIVES: To delineate laboratory-confirmed bloodstream infection (LCBI), analyze risk factors for its occurrence and predictors for its short-term mortality in systemic lupus erythematosus (SLE) patients.Methods A single center, retrospective, case-controlled study was performed in 159 SLE patients (2013-2019) to identify risk factors of LCBI by comparing patients with LCBI (n = 39) to those without infection (n = 120). The predictors associated with 30-day mortality in LCBI patients were also analyzed. RESULTS: Altogether 40 bacteria strains were isolated in 39 LCBI patients with a predominance of the gram-negative bacilli (24 strains, 60.0%). Escherichia coli and Staphylococcus aureus were the leading Gram-negative and Gram-positive microorganisms, respectively. Occurrence of LCBI was independently predicted by: SLE disease duration >4 years, SLEDAI score >4 points, glucocorticoids dose >7.5 mg/d and the previous or concomitant occurrence of autoimmune hemolytic anemia (AIHA) or thrombotic microangiopathy (TMA). Based on the identified risk factors, we developed a matrix model for the risk of future LCBI. The 30-day mortality (39 cases) was 23.1% and healthcare-associated LCBI was a predictor for 30-day mortality in SLE patients compared with community-acquired LCBI. CONCLUSION: Longer duration, higher disease activity and glucocorticoids dose, and occurrence of AIHA or TMA were risk factors of LCBI in SLE and its poor short-term prognosis may attribute to healthcare-associated LCBI.

Innate lymphoid cells are increased in systemic lupus erythematosus.

OBJECTIVES: Innate lymphoid cells (ILCs) are emerging mediators of immunity and accumulation of inflammatory ILC populations can occur in inflammatory-mediated conditions. We aimed to examine the proportion of different subgroups of ILCs in the peripheral blood of patients with systemic lupus erythematosus (SLE) to evaluate the pathogenesis of SLE. METHODS: Peripheral blood mononuclear cells were collected from 51 SLE patients and 26 healthy controls. Subpopulations of ILCs were analysed by flow cytometry. RESULTS: Compared with the control group, ILCs (Lin-CD127+CD45+ cells) were higher in SLE patients (p<0.01), and the distribution of ILC population changed between groups, ILC1 (Lin-CD127+CD45+CRTH2-CD117-cells)/ILC3 (Lin-CD127+CD45+CRTH2-CD-117+cells) count increased (p<0.0001) and correlated with nephritis and disease activity. CONCLUSIONS: We found that SLE is accompanied by alterations in circulating ILCs. Specifically, circulating ILC1s and ILC3s were significantly increased, whereas circulating ILC2s were significantly decreased in SLE, indicating abnormal ILC homeostasis.

Predictive factors and prognosis of macrophage activation syndrome associated with adult-onset Still's disease.

OBJECTIVES: To summarise the clinical data of adult-onset Still's disease (AOSD) patients and analyse their clinical manifestations, predictors for the formation and prognosis of macrophage activation syndrome (MAS). METHODS: A retrospective analysis was performed on the clinical data of 182 AOSD hospitalised patients from the Department of Rheumatology of the First Affiliated Hospital of Zhengzhou University, China from January 2012 to August 2018, including 11 patients with pathogenesis of MAS. RESULTS: Compared with the patients without MAS, the patients with MAS had a higher incidence of splenomegaly and pericarditis at the initial diagnosis of AOSD. The number of platelets (PLT) and the concentration of fibrinogen (FIB), D-Dimer and ferritin were significantly higher in AOSD-MAS patients. Multivariate regression analysis showed that splenomegaly (OR: 5.748, 95% CI: 1.378-23.984, p=0.016), pericarditis (OR: 6.492, 95% CI: 1.43-29.461, p=0.015), and ferritin >2000 µg/L (OR: 4.715, 95% CI: 1.12-19.86, p=0.035) were risk factors for MAS. Survival analysis indicated that the mortality of AOSD-MAS patients was significantly higher than patients without MAS. CONCLUSIONS: Splenomegaly, pericarditis and elevated ferritin concentration are risk factors for MAS formation in AOSD patients. MAS resulted in a significant decrease in the survival rate of the AOSD patients.

Folate Supplementation for Methotrexate Therapy in Patients With Rheumatoid Arthritis: A Systematic Review.

OBJECTIVE: To review the evidence for benefits and harms of folate (folic acid or folinic acid) supplementation on methotrexate (MTX) treatment for rheumatoid arthritis (RA), to assess whether or not folate supplementation would reduce MTX toxicity or reduce MTX benefits, and to decide whether a higher MTX dosage is essential. METHODS: We performed a sensitive search strategy and searched systematically the Medline, Embase, Web of Science and Cochrane Library databases from inception to 2 June 2016. Abstracts from major rheumatology meetings and major trial registers were also searched to retrieve all randomized controlled trials that interested us. RESULTS: Seven studies with 709 patients were included. No significant heterogeneity was found between these trials. For RA patients treated with MTX, those supplied with folate were less likely to have elevated transaminase (odds ratio [OR] 0.15; 95% confidence interval [95% CI] 0.10, 0.23 [p < 0.00001]) and gastrointestinal side-effects such as nausea and vomiting (OR 0.71; 95% CI 0.51, 0.99 [p = 0.04]). Folate appeared to promote compliance to MTX as it reduced patient withdrawal compared to placebo (OR 0.29; 95% CI 0.21, 0.42 [p < 0.00001]). There was no statistical difference for mouth sores between folate and placebo (OR 0.83; 95% CI 0.57, 1.22 [p = 0.35]). As the markers of disease activity in those trials were not consistent, it was impossible to decide whether folate supplementation reduced MTX efficacy. Besides, we compared high-dose folate (≥25 mg per week) and low-dose folate (≤10 mg per week) on MTX efficacy, finding no statistical difference (OR 2.07; 95% CI 0.81, 5.30 [p = 0.13]), nor on MTX toxicity (OR 1.56; 95% CI 0.80,3.04 [p = 0.19]). CONCLUSION: Folate supplementation can reduce the incidence of hepatotoxicity and gastrointestinal side-effects of MTX in patients with RA. It can also reduce patient withdrawal from MTX treatment. Although it tended to reduce mouth sores, it had no statistical significance. No significant difference was found between high-dose folate and low-dose folate on MTX efficacy or toxicity.

Chinese lupus treatment and research group (CSTAR) registry: X. family history in relation to lupus clinical and immunological manifestations.

OBJECTIVES: This study aimed to examine the associations between family history and clinical manifestations and immunologic characteristics of lupus in China. METHODS: Based on their family history, lupus patients from the Chinese lupus treatment and research group (CSTAR) registry were categorised: familial lupus (FL), family history of other rheumatic disorders (RD), and sporadic lupus (SL). Demographic data, clinical manifestations, and laboratory data were compared among these three groups. RESULTS: A total of 2,104 patients from CSTAR were included, with 34 (1.6%) in the FL group, 50 (2.4%) in the RD group, and 2,020 (96.0%) in the SL group. There were no significant differences in age or gender among these groups (p=0.36 and p=0.75, respectively). The prevalence of discoid rash and positivity of anti-RNP antibodies differed significantly among the three groups. Photosensitivity and neurological disorder were marginally significantly different among the three groups (p=0.05). No statistical differences were observed in other clinical manifestations or laboratory results. In the FL group, first-degree relatives (25/34, 73.5%) had higher susceptibility to lupus. Rheumatoid arthritis (RA) (35/50, 70.0%) was the most frequent non-lupus rheumatic disorder in the RD group. CONCLUSIONS: Among lupus patients, the rate of familial lupus was lower in Chinese patients than among other ethnicities. Familial lupus cases are found mainly among their first-degree relatives. A family history of lupus did not significantly affect clinical phenotypes, except for higher frequency of discoid rash and anti-RNP in the FL group, and more anti-RNP positivity in the RD group.

Chinese registry of rheumatoid arthritis (CREDIT): I. Introduction and prevalence of remission in Chinese patients with rheumatoid arthritis.

OBJECTIVES: To introduce the Chinese Registry of rhEumatoiD arthrITis (CREDIT), which is the first nationwide, multicentre, online rheumatoid arthritis (RA) registry in China, and to depict major cross-sectional data and treatment strategies of Chinese RA patients. METHODS: RA patients who fulfilled the 2010 ACR/EULAR classification criteria for rheumatoid arthritis were recruited into the registry by their rheumatologists from 144 clinical centres in China. Data, including demographics, disease characteristics, co-morbidities, treatment, and adverse reactions, were collected and documented through the predefined protocol. RESULTS: 8071 registered patients (F:M = 4.03:1) were registered up to May 2017. Mean age at symptom onset and at diagnosis was 46.15±14.72y and 48.68±14.54y, respectively. Point prevalence of remission (95% CIs) was 14.88% (14.10-15.66%), 4.23% (3.79-4.66%), 4.25% (3.81-4.69%), and 4.27% (3.83-4.72%) according to DAS28-CRP, CDAI, SDAI, and the 2011 ACR/EULAR remission criteria, respectively. 38.84% and 38.11% of treatment-naïve patients (n=3262) were in moderate (3.25.1) disease activity, respectively. Among treatment-naïve patients, those who were initiated on treatment with bDMARDs had higher disease activity than those who were treated with csDMARDs (p<0.05). Three months after initiating bDMARDs, 19.29% (n=38) of patients achieved remission (DAS28-CRP<2.6). CONCLUSIONS: The CREDIT registry is an effective tool for real-world study of RA patients in China. By providing information for diagnosis and treatment regimen, the CREDIT registry can enhance the application of treat-to-target (T2T) strategy and improve patient outcomes in China.