1.Change of serum interleukin-23 levels and sacroiliac joint magnetic resonance imaging before and after treatment with recombinant human tumor necrosis factor-α receptor Ⅱ IgG Fc fusion protein for injection in axial spondyloarthritis patients
Peipei SU ; Cundong MI ; Cheng ZHAO ; Zhanrui CHEN ; Fang QIN
Chinese Journal of Rheumatology 2015;19(3):160-164,后插1
Objective We investigated interleukin (IL)-23 that might play a role in the pathogenesis of rheumatoid arthritis (RA) and whether it was correlated with disease activity and clinical manifestations in axial spondyloarthritis (SPA).In addition, the Spondyloarthritis Research Consortium of Canada (SPARCC) scores was used to examine whether recombinant human tumor necrosis factor-α receptor Ⅱ IgG Fc fusion protein for injection (rhTNFR:Fc) was effective for the reduction of magnetic resonance imaging (MRI)-proven sacroiliac joint (SIJ) inflammation.Methods The serum IL-23 levels of etanercept and conven-tional treatment groups were measured using enzyme-linked immunosorbent assay kits.At the same time, SIJ MRI SPARCC score levels were assessed by MRI, the change of clinical indicators of patients was observed.ANOVA, repeated measure data of ANOVA and Spearman's correlation analysis were used for statisical analysis.Results ① The basal serum IL-23 levels of the Etanercept group were (34.2±1.8) pg/ml and those of the conventional treatment group were (34.1 ±1.8) pg/ml (F=1 073.790, P=0.991), both were significantly higher than the healthy control group (18.1±0.8) pg/ml (P=0.005).After treatment, serum IL-23 levels of the rhTNFR: Fc treatment and conventional treatment group were (24.5 ±1.7) pg/ml and (25.2±1.7) pg/ml (F=232.488, P=0.242), (19.2±0.8) pg/ml and (21.6±1.3) pg/ml (F=114.135, P=0.025), (19.0±0.8) pg/ml and(19.4± 0.8) pg/ml (F=23.374, P=0.085) respectively.A significant decrease was observed in the two groups and the serum level of IL-23 of the rhTNFR:Fc group was lower than that of the conventional group at week 12.② SIJ MRI SPARCC scores of the rhTNFR:Fc group and the conventional drugs group were (20.1± 1.2) scores and(20.7±1.5) scores (F=2003.660, P=0.191), (12.5± 0.8) scores and (15.4±0.9) scores (F=1 680.430, P=0.004), (8.8±0.9) scores and (12.8± 0.9) scores (F=972.877, P=0.002), the scores of two group were significantly decreased after treatment.At week 12, 24 of the treatment, the rhTNFR:Fc group scores were lower than the conventional drugs group.③ The serum IL-23 levels, SLJ MRI SPARCC scores and clinical index (ESR, CRP, PGA, BASDAI, BASFI, BASMI and number of painful joints) were not correlated (P>0.05), the SIJ MRI SPARCC scores and clinical indicators were not correlated (P>0.05).Conclusion ① The serum IL-23 levels of the rhTNFR:Fc are higher than healthy controls.② rhTNFR:Fc treatment could significantly decrease IL-23 levels and improve the sacroiliac joint inflammation compared to conventional treatment.③ SIJ MRI is a good assessment method for the detection of SpA sacroiliac joint inflammation.
2.The clinical significance of serum interleukin-17 in rheumatoid arthritis
Cundong MI ; Dan GUO ; Cheng ZHAO ; Zhanrui CHEN
Chinese Journal of Rheumatology 2010;14(3):182-184
Objective To investigate the serum concentration of interleukin (IL)-17 in patients with active rheumatoid arthritis and the clinical implication. Methods Serum IL-17 level of 51 active RA patients were assessed by enzyme-linked immunosorbentassay (ELISA). The relationship between serum levels of IL-17 in active RA patients and clinic features were analyzed. Two independent samples t test, ANOVA for repeated, one-way ANOVA and Spearman's Chi-square test were used for statistical analysis. Results ① Serum IL-17 levels were elevated in active RA patients (365±63) pg/ml than in normal controls (86±13) pg/ml (P<0.01); ② Serum IL-17 levels in active RA was correlated with morning stiffiness duration, swelling index, Ritchie index, CRP, ESR, RF, X-ray score, DAS score (r =0.423, 0.213, 0.252, 0.276, 0.346, 0.251, 0.412, 0.398; P<0.05). ③ The levels of IL-17 between phase I (296±79) pg/ml and Phase II (360±89) pg/ml, phase II and phase HI (464±74) pg/ml, Phase I and Phase Ⅳ (369±83) pg/ml in RA group were statistically significantly different (P<0.05). Conclusion The levels of serum IL-17 in active RA patients are higher than the normal controls. The elevated serum IL-17 levels may be the useful markers for active RA.In addition,interleukin-17 is involved in disease progression and bony erosion of RA, and it maybe a new treatmenttarget of RA.
3.The expression and significance of vascular endothelial growth factor and its soluble receptor sFlt-1 in the serum of patients with systemic lupus erythematosus
Cheng ZHAO ; Fan RONG ; Qiaoyuan WU ; Cundong MI ; Zhanrui CHEN ; Yunhua LIAO ; Wei LI
Chinese Journal of Rheumatology 2009;13(3):162-165
Objective To investigate the serum concentration of vascular endothelial growth factor (VEGF) and its soluble receptor 1 (sFlt-1) in patients with systemic lupus erythematosus (SLE) and its correlation with clinic and pathologic parameters.Methods serum levels of VEGF and sFlt-1 in a group of 60 patients with SLE and 30 healthy controls were assessed by ELISA.Results The VEGF and sFlt-1 serum levels were higher in active SLE group than the control group (P<0.01).The VEGF/sFlt-1 ratio in the control group was lower than that in the active SLE group.inactive SLE group and LN group (P<0.01).Particularly the ratio increased in WHO class Ⅴ LN group compared to WHO classⅡ,Ⅲ,Ⅳ LN group (P<0.05).The semm level of sFlt-1 was correlated to proteinuria (rs=0.6244,P<0.01) and ESR (rs=0.4235,P<0.01) and the serum levels of VEGF and sFlt-1 were correlated to the systemic lupus erythematosus disease activation index (SLEDAI) (rs=0.5046,P<0.01 and rs=0.5152,P<0.01,respectively).The serum level of VEGF was correlated with renal tissue activation index (RAI) (rs=0.3386.P<0.05) and the serum levels of VEGF and sFlt-1 were not correlated to blood pressure,serum creatine,blood ureanitmgen,C3,C4,C-reative protein.The muhi-factors stepwise regression analysis indicated that serum VEGF was positively correlated with SLEDAI (R2=0.1 75,P<0.05),serum sFlt-1 was positively correlated with ESR and proteinurine (R2=0.497,P<0.05).Conclusion Serum VEGF and sFlt-1 are elevated in patients with active SLE and they can reflect the activity of the disease.The overcxpression of serum VEGF might be correlated to the proliferated glomerulonephritis and the overexpression of sFlt-1 contribhtes to proteinurla.The imbalance between these two factors may act an important role in SLE pathogenesis.
4.Clinical analysis of 34 cases with diffuse alveolar hemorrhage in systemic lupus erythematosus
Zichen HUANG ; Hejun WANG ; Cheng ZHAO ; Leting ZHENG ; Jing WEN ; Zhanrui CHEN ; Ling LEI
The Journal of Practical Medicine 2018;34(1):100-102,106
Objective To identify the clinical characteristics and therapeutic effect of systemic lupus erythematosus (SLE) patients with diffuse alveolar hemorrhage (DAH).Methods Clinical characteristcs,diagnosis,treatment and outcome in 34 patients hospitalized in The First Affiliated Hospital of Guangxi Medical University from January 2006 to December 2016 were retrospectively analyzed.Results The incidence of DAH involvement of SLE was about 0.39%.Median age was 19 (interquartile range (IQR) 11.75 ~ 32) years.The duration of SLE before clinical DAH was 6 months (IQR 2 ~ 15.75) months.The main clinical manifestations of DAH were cough,dyspnea and fever.The SLE disease activity index (SLEDAI) score was 19.5 (16 ~ 25)points and anti-dsDNA antibody titer elevated markedly (38.2%).The overall mortality rate was 73.5%,however patients who chose department of rheumatism have lower mortality (52.9%).And treatment of CTX was associated with mortality (OR =0.059,95% CI 0.006 ~ 0.554,P =0.013),as well as steroids and immunosuppressant combination therapy.Conclusions The clinical symptoms of SLE with DAH is often atypical.There is manifestation of cough,fever,dyspnea and etc.Imaging and broncoscopy can assist the diagnosis and its prone to the pulmonary infection and high mortality.Early diagnosis and application of CTX combined with conventional dose of hormone theraphy can in early diagnosis and reduce the mortality.
5.Analyses of the factors that influence the quality of life of patients with systemic sclerosis
Ling LEI ; Shenbin SU ; Cheng ZHAO ; Zhanrui CHEN ; Fang QIN ; Jing WEN
Chinese Journal of Rheumatology 2018;22(10):654-659
Objective To study the factors that may influence the quality of life (QoL) in patients with systemic sclerosis (SSc) by comprehensively evaluating of the patient's condition and to provide evidence for appropriate selection of treatment.Methods Out-patients with SSc in the First Affiliated Hospital of Guangxi Medical University from November 2015 to October 2016 were retrospectively enrolled into this cross-sectional study.Their clinical data were collected.Consecutive SSc patients and 30 healthy controls were recruited and were assessed by the MOS-36 Item Short-Form Health Survey (SF-36),Health Assessment Questionnaire (HAQ),Visual Analogue Scale (VAS) and the St.George's Respiratory Questionaire (SGRQ).The extent of skin involvement of SSc was assessed by the Modified Rodnan skin score (MRSS).The SSc group was divided to diffused SSc (dcSSc) and localized SSc (lcSSc) according's to extent of skin involvement.Pearson's correlation analysis was used to assess the associated clinical indications with the QoL.Results ① Sixty-eight SSc patients were studied [mean age (52±11) years,mean disease duration (35±48) months],in which 59(87%)patients had Raynaud's pheno-menon,9(13%) patients hadfinger ulcer,16(24%) patients were complicated with PAH,and anti-Scl-70 antibody was positive in 59(87%) cases.② The SSc patients had significantly lower SF-36 scale score,including physical function (PF) (64±29),role-physical (RP) (53 ±33),bodily pain (BP)(66±19),social function (SF) (53±20),general health (GH) (58±24),vitality (VT) (53±18),role emotional (RE)(47±35),mental health (MH) (45±21),compared with the healthy-control group (t=7.726,7.132,8.586,12.29,8.296,9.526,6.893,13.973,4.384),all P<0.01).The SSc patients had significantly higher scale scores of HAQ (t=1 1.823),VAS (t=19.578) and SGRQ (t=14.043,16.688,21.210,20.053),all P<0.01.③ Compared with lcSSc patients,the SF-36 of dcSSc patient in the PF (F=17.035,P=0.030),RP (F=17.579,P=0.033),BP (F=23.002,P=0.032),VT (F=35.737,P=0.008) were decreased.The HAQ and VAS scale of dcSSc patients were significantly higher than lcSSc patients (F=42.541 and 110.243,P<0.01).④ The PF,RP,VT,SF,MH of SF-36 scale score in SSc patients was inversely associated with HRCT scores (r=-5.088,-2.896,-2.566,-3.450,-4.173),MRSS (r=-3.847,-3.044,-2.651,-2.571,-2.455),but positively correlated with Complement3 (C3)(r=2.372,2.133,2.370,2.493,2.387).BP,and HAQ scores,VAS were associated with Raynaud's phenomenon (r=2.502,-2.683,-3.703) and MRSS (r=2.141,-2.683,-3.703).And VAS score was correlated with arthralgia (r=-2.943).The symptom score,activity score,influence score of SGRQ were negatively associated with HRCT score (r=4.001,-3.213,2.478),smoking-state (r=-3.040,-2.007,-2.218),all P<0.05.Conclusion The SSc patients have impaired physical and mental function in the QoL,limited mobility,increased physical pain compared to healthy controls.DcSSc patients have worse QoL index compared with lcSSc patients.For SSc patients with pulmonary fibrosis,extensive skin involvement,high C3 level might have poor QoL.
6.Clinical characteristics and risk factors of gastrointestinal involvement in patients with systemic lupus erythematosus
Ling LEI ; Xiaofen LI ; Zhanrui CHEN ; Fang QIN ; Jing WEN ; Fei DONG ; Jie PAN ; Xiaoling LIAO ; Cheng ZHAO
Chinese Journal of Rheumatology 2022;26(3):160-167
Objective:To study the clinical features and prognostic risk factors of gastrointestinal (GI) involvement in systemic lupus erythematosus (SLE), and improve clinicians' understanding of GI involvement in SLE.Methods:The clinical data of SLE patients admitted to the First Affiliated Hospital of Guangxi Medical University from September 1, 2012 to September 1, 2019 were retrospectively analyzed. Two hundred and forty-three patients with GI system involvement were the GI system affected group, and 486 patients with-out GI system involvement at the same period were randomly selected as the control group. The clinical mani-festations, laboratory tests and treatment effects of the two groups were compared by t test, Wilcoxon signed-rank test and χ2 test and Logistic regression was used to analyze the prognostic risk of SLE with GI system involvement. Results:① There were 243 SLE patients with GI involvement, with the proportion of GI involvement in SLE patients of 6.4%(243/3 820), and as the first manifestation with GI system symptoms accounted for 20.2%(49/243). The common causes were lupus hepatitis accounted for 52.3%(127/243), lupus mesenteric vasculitis (LMV) for 35.0%(85/243), pseudo Intestinal obstruction (IPO) for 9.9%(24/243), lupus-related pancreatitis for 8.6%(21/243), and protein-losing enteropathy (PLE) as 7.0%(17/243). ② Compared with the control group, the group with GI involvement had a lower average age [(38±14) year vs(32±15) year, t=-2.47, P=0.014], a shorter median duration of illness [12.0(3.0, 72.0) months vs 5.0(1.1, 24.8) months, Z=-5.67 , P<0.001], a higher median systemic lupus erythematosus disease activity index (SLEDAI) score [10(6,28) vs 16(9, 37), Z=2.24 , P<0.001], the occurrence of skin rash (38.7% vs 53.5%, χ2=14.46), arthritis (36.4% vs 46.7%, χ2=7.12 , P=0.008), myositis (43.0% vs 56.4%, χ2=11.53 , P=0.001), pericarditis [(216±111)×10 9/L vs (175±114)×10 9/L, t=-4.69 , P<0.001], thrombocytopenia, and hydroureterosis (1.0% vs 12.8%, χ2=47.47 , P<0.001) were high, but the incidence of pulmonary arterial hypertension (PAH) (31.2% vs 10.7%, χ2=36.99 , P<0.001) was low; Serum alanine aminotransferase (ALT) [17(10, 29) U/L vs 59(16, 127) U/L, Z=9.65 , P<0.001], aspartate aminotransferase (AST) [25.0 (18.0, 37.0) U/L vs 82.5(25.0, 289.0) U/L, Z=10.57 , P<0.001], alkaline phosphatase (ALP) [58(46, 76) U/L vs 82(56, 187)U/L, Z=8.42 , P<0.001], Creatine kinase (CK) [44.0(28.0, 83.0) U/L vs 58.5(34.0, 176.0) U/L, Z=4.46 , P<0.001], lactate dehydrogenase (LDH) [(309±206) U/L vs (443±332) U/L, t=5.64 , P<0.001], fasting blood glucose (FBS) [(5.0±1.5) mmol/L vs (5.3±1.7) mmol/L, t=2.16 , P=0.031], triglyceride (TG) [(2.0±1.3) mmol/L vs (2.7±2.2) mmol/L, t=4.55 , P<0.001] increased, albumin (ALB) [(30±7) g/L vs (27±7) g/L, t=5.87 , P<0.001)] and high-density lipoprotein (HDL) [(1.1±0.8) mmol/L vs (0.9±0.5) mmol/L, t=-4.20 , P<0.001] decrease, and anti SSB antibody positive rate (16.0% vs 9.5%, χ2=5.60 , P=0.018) decreased.③ After 3 months' follow-up, 203 patients with SLE GI involvement were relieved, 30 patients (12.3%) died, and 9 patients (1.8%) died in the control group. Ninety-five (46.8%) patients in the remission group had a significantly higher rate of cyclophosphamide treatment when compared with 5(12.5%) in the non-remission group ( χ2=16.23, P<0.001) . Logistic regression analysis showed that no increase of PAH, elevated erythrocyte sedimentation rate (ESR), ALT, glutamyl transpeptidase (GGT), indirect bilirubin (IBIL) and high SLEDAI scores, hydroureteral dilatation, decreased ALB and HDL were independent related factors for SLE GI involvement, while ascites and elevated FBS were SLE GI involvement factors of poor prognosis. Conclusion:SLE patients with GI involvement have a high mortality rate, and lupus hepatitis and LMV are common. Hydroureterosis, high SLEDAI score, abnormal liver function are risk factors for GI involvement. Jaundice and elevated FBS are the risk factors for poor prognosis, and treatment with cyclophosphamide is the protective factor.
7.Advances in extracorporeal photopheresis
Zhanrui CHENG ; Yujie KONG ; Li TIAN ; Zhong LIU
Chinese Journal of Blood Transfusion 2022;35(7):776-782
Extracorporeal photopheresis(ECP) is a bidirectional cellular immunomodulatory therapy based on leukapheresis, which can mediate not only immunopotentiation but also immunosuppression. Clinically, ECP has been observed to have good efficacy in the treatment of cutaneous T cell lymphoma(CTCL), graft versus-host disease(GVHD) and solid organ transplant rejection, also the US Food and Drug Administration(FDA) has approved ECP for the treatment of CTCL. The treatment guidelines for GVHD in the US and Europe also include ECP, however, there is a lack of relevant guidelines in China. Although the exact mechanism of ECP is not fully explained, recent studies provide a theoretical basis for a further understanding of the bidirectional regulation of ECP.The initial hypothesis was the combination of 8-methoxypsoralen(8-MOP) and ultraviolet A(UVA) to induce apoptosis of immune cells. As the research progressed, this idea was transformed into the differentiation of monocyte to dendritic cell(DC), cytokine alteration and the regulatory T cell(Treg) stimulation.In this article, the current exploration of the immunomodulatory mechanism in ECP and its clinical application were reviewed, also the latest molecular mechanism of ECP mediated immunopotentiation and immunosuppression was comprehensively analyzed, meanwhile the further promotion and clinical application of ECP in China had been prospected.
8.Effect and mechanism of extracorporeal photopheresis on preventing acute graft versus host disease in ice
Zhanrui CHENG ; Yuwei LIN ; Yan ZHONG ; Along ZHANG ; Haixia XU ; Li TIAN ; Zhong LIU
Chinese Journal of Blood Transfusion 2023;36(10):860-867
【Objective】 To investigate the preventive effects of early apoptotic splenic mononuclear cells induced by extracorporeal photopheresis (ECP) on acute graft versus host disease (aGVHD) in mice and explore the underlying mechanisms. 【Methods】 1) Splenic mononuclear cells were extracted from C57BL/6 mice and treated with different concentrations of 8-MOP (50 ng/mL, 100 ng/mL, 200 ng/mL, 300 ng/mL, 600 ng/mL). After treatment, irradiate the cells with 2 J/cm2 of ultraviolet light. Then, use the Annexin V-FITC/PI apoptosis detection kit to assess the early apoptosis rate of the cells and determine the optimal concentration of 8-MOP for the experiment.2) There were 35 SPF-grade female BALB/C mice (H-2Kd) aged 6-8 weeks. After whole-body irradiation with 8Gy X-rays, the mice were divided into five groups: sham irradiation group received intravenous infusion of 0.2 mL of normal saline, the syngeneic bone marrow transplantation group received intravenous infusion of 0.2 mL of BALB/C mouse bone marrow nucleated cell suspension (including a cell count of 1×107), the allogeneic bone marrow transplantation group received intravenous infusion of 0.2 mL of C57BL/6 mouse bone marrow nucleated cell suspension (including a cell count of 1×107), the aGVHD group received intravenous injection of a mixture of C57BL/6 mouse bone marrow nucleated cells (including a cell count of 1×107) and splenic mononuclear cells (including a cell count of 1×107) in 0.2 mL, the ECP prevention group received pre-transplant intravenous infusion of 0.2 mL of ECP-treated splenic mononuclear cells of C57BL/6 mice (including a cell count of 1×107 ) 48 hours before transplantation, and on the day of transplantation, intravenous injection of a mixture of C57BL/6 mouse bone marrow nucleated cells (including a cell count of 1×107) and splenic mononuclear cells (including a cell count of 1×107 ) in 0.2 mL.The preventive effects of ECP on aGVHD were observed, and the concentrations of IFN-γ, IL-2, TNF, IL-4 and IL-6 in mouse serum were measured using CBA. Th1 cell counts were determined by flow cytometry. 【Results】 Different concentrations of 8-MOP (50 ng/mL,100 ng/mL, 200 ng/mL, 300 ng/mL, 600 ng/mL) were used to treat mouse splenic mononuclear cells. The early apoptosis rates (%), observed after treatment were as follows: (14.18±0.865) vs (16.76±0.407) vs (18.83±0.404) vs (19.27±0.404) vs (14.5±0.529). The appropriate concentration of 8-MOP was determined to be 200 ng/mL.In vivo experiment, the results showed that the aGVHD group had decreased survival rate, reduced body weight, and increased clinical scores compared to the syngeneic and allogeneic bone marrow transplantation groups (P<0.01), and the chimerism of bone marrow cells in mice after transplantation was over 90%. ECP significantly improved the survival rate of mice after transplantation, reduced clinical scores (P<0.05), and decreased the concentrations of Th1 cell cytokines in serum (P<0.05) and the counts of Th1 cells in the spleen (P<0.05). 【Conclusion】 ECP-induced early apoptotic single nuclear cells from the spleen can prevent the occurrence of aGVHD by reducing the Th1 response in mouse.