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Objective:To explore the distribution characteristics of memory B cells and its relationship with bone erosion in patients with rheumatoid arthritis (RA), and to further understand the mechanism of B cells in the pathogenesis of RA.Methods:B cell subsets in peripheral blood of 200 RA patients and 50 healthy individuals were detected by flow cytometry. According to the surface markers CD19, CD27 and lgD, B cells were divided into CD19 +CD27 +lgD - switched memory B cells, CD19 +CD27 +lgD + non-switched memory B cells, CD19 +CD27 -lgD - double-negative memory B cells and CD19 +CD27 -lgD + naive B cells. B cells in RA patients with various disease activity score, course of disease and treatment were analyzed. Patients were divided into four groups according to the results of joint ultrasonography, including patients without bone erosion, patients with hand bone erosion, patients with knee bone erosion and patients with hand and knee bone erosion. The relationship between the distribution of B cell subsets, autoantibodies and RA bone erosion were analyzed. Differences between the groups were analyzed by independent-samples t test, Mann-Whitney U test and χ2 test. The analysis of variance, Kruskal-Wallis analysis were used for multi-group comparison, Spearman correlation analysis was also used for correlation analysis. Results:①RA patients showed significantly decreased non-switched memory B cells [(9.5±6.7)% vs (12.1±4.7)%, t=2.46, P=0.015] and increased double negative memory B cells [(3.8±2.5)% vs(2.7±1.3)%, t=-4.74, P<0.001] in comparison to healthy individuals. The percentage of non-switched memory B cells were decreased in RA patients with moderate disease activity [(8.4±4.7 )% vs (12.4±7.5)%, t=3.13, P=0.001] and high disease activity [(7.8±7.6)% vs (12.4±7.5)%, t=3.00, P=0.003] in comparison to those in RA patients who achieved remission. Meanwhile, the na?ve B cells [(70.3±15.0)% vs (63.9±14.6)%, t=-2.15, P=0.034] were increased in RA patients with moderate disease activity. No difference was found in RA patients with different disease courses. Total B cells [(4.8±2.9)% vs (7.2±4.1)%, t=-3.24, P=0.001], non-switched memory B cells (7.6±4.3)% vs (10.0±7.1)%, t=-2.63, P=0.010) in RA patients who received prednisone treatment were decreased, while double-negative memory B cells (4.9±3.0)% vs (3.6±2.3)%, t=-2.79, P=0.006] were increased compared with those in RA patients without prednisone treatment. Non-switched memory B cells was decreased in RA patients with hand and knee erosion compared with RA patients without erosion [6.8%(2.5%, 9.5%) vs 9.7%(5.5%, 17.5%), Z=-2.12, P=0.034]. Double negative memory B cells in subgroup with keen erosion [3.3%(2.7%, 5.0%) vs 2.6%(1.9%, 3.8%), Z=-2.09, P=0.036]as well as with hand and knee erosion [3.9%(2.3%, 5.6%) vs 2.6%(1.9%, 3.8%), Z=-2.41, P=0.016] were higher than those in patients without erosion. In addition, higher serum RF level was found in subgroup RA patients with hand and knee erosion compared with subgroup of RA patients without erosion [141.0 (38.0, 874.0) U/ml vs 53.5 (10.0, 106.0)U/ml, Z=-2.07, P=0.039]. Meanwhile, the positive rate of ACPA in RA patients with bone erosion of hand was significantly higher than that of RA patients without bone erosion [81%(52/64) vs 64%(38/59), χ2=4.44, P=0.043). Conclusions:The results suggest that the increase of double negative memory B cells, the decrease of non-switched memory B cells and higher level of autoantibodies may closely relate to bone erosion of RA, which may be one of the pathogenesis of disability in RA.
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Objective To explore the prevalence of vitamin D deficiency in the new onset and treatment-naive systemic lupus erythematosus (SLE) patients and study the correlation between serum 25(OH)D values and disease activity of SLE. Methods A retrospective case series analysis was done in 117 new-onset and treatment-na?ve SLE hospitalized patients during May 2016 and May 2017 in the Department of Rheumatology of the First Affiliated Hospital of Xi'an Jiaotong University and 39 age and gender matched healthy controls. Cinical and demographic details were collected. Disease activity of SLE was evaluated according to the systemic lupus erythematosus disease activity index (SLEDAI) score. The t-test, Mann-Whitney U test, Chi-square test, Spearman rank correlation coefficient test and multivariate linear regres sion were performed. Results Among the 117 SLE patients, 102 were female (87.2％) with the mean age of (36 ± 15) years. The median duration before diagnosis was 5(1, 12) months and the mean SLEDAI score was (12 ±7). The mean level of 25(OH)D was significantly lower in SLE patients [(10.1±6.0) ng/ml] than in healthy controls [(17 ±8) ng/ml, t=-5.273, P<0.01 ], and the prevalence of vitamin D deficiency was higher in SLE patients (109/117, 93.2％) than in healthy controls (28/39, 71.8％, x2=12.486, P<0.01). With 10 ng/ml as the cut-off point of serum 25 (OH)D, patients were divided into two groups. The percentages of haematological damage (84.3％ vs 66.0％, x2=5.321, P=0.021), lupus nephritis (32.9％ vs 14.9％, x2=4.759, P=0.029) and serositis (28.6％ vs 8.5％, x2=6.940, P=0.008), SLEDAI score [(13±8) vs (9±5), t=3.503, P=0.001)] and 24-hour urinary protein [(0.57±1.05) vs (0.21±0.46), t=2.437, P=0.017] were significantly higher in the 25 (OH)D<10 ng/ml group, but complement C3 [(0.5±0.3) g/L vs (0.7±0.3) g/L t=-2.441, P=0.016] and hemoglobin [(93±19) g/L vs (104 ±19) g/L, t=-3.052, P=0.003) were significantly lower in this group. The differences were statistically significant. SLEDAI score (r=-0.433, P=0.000), 24-hour urinary protein (r=-0.434, P=0.000)was significantly inversely correlated and complement C3 (r=0.296, P=0.001), hemoglobin (r=0.323, P=0.000) was significantly positively correlated with serum 25(OH)D level. There was an independent inverse correlation between SLEDAI score and serum 25(OH)D levels (β=-0.376, P=0.000). Conclusion The prevalence of vitamin D deficiency in the new-onset and treatment-naive systemic lupus erythematosus patients is significantly higher than that in healthy controls. There is an independent inverse correlation between serum 25 (OH)D values and disease activity of SLE.
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Objective To investigate the effect of intra-articular tumor necrosis factor (TNF) inhibitor injection in patients with moderate to severe rheumatoid arthritis (RA) and values of power Doppler ultrasonography in evaluating effect of intra-articular injection.Methods RA patients with arthritis in knee and/or elbow and/or ankle referred to the Department of Rheumatology in the First Affiliated Hospital of Xi'an Jiaotong University were enrolled to receive intra-articular injection with 50 mg or 25 mg of recombinant human tumor necrosis factor-α receptor Ⅱ:IgG Fc fusion protein (TNFR:Fc) for injection after synovial fluid aspiration.Evaluation of visual analogue scale for pain of the involved joints,erythrocyte sedimentation rate (ESR),C reactive protein (CRP) and 28-joint disease activity score (DAS28) were performed before and after intra-articular TNFR:Fc injection.Synovial hypertrophy,power Doppler signal and joint effusion were analyzed and graded by ultrasound before and after intra-articular TNFR:Fc injection.Comparisons of continuous data between groups was made by t test.The data that were not normally distributed was analyzed by Mann-Whitney U rank sum test.Results Fifty-four patients with RA [6 men and 48 women,mean age (52±11) years,mean duration of disease (7±3) years] were included in this study.A significant decrease in visual analogue scale for pain of the involved joints (t=2.630,P=0.018;t=2.160,P=0.043),ESR (t=2.094,P=0.030;Z=-2.242,P=0.030),CRP (Z=-2.199,P=0.030;Z=-3.337,P=0.001) and DAS28 (t=3.579,P=0.002;t=5.538,P=0.000) were observed after one month of injection of 50 mg or 25 mg of TNFR:Fc.Synovial hypertrophy (t=2.175,P=0.036;t=2.280,P=0.030) power Doppler signal (t=2.500,P=0.020;Z=-2.504,P=0.013) and joint effusion (Z=-1.790,P=0.042;t=2.230,P=0.027) were reduced significantly after one month of intra-articular TNFR:Fc injection in knee.Synovial hypertrophy (t=2.180,P=0.034;t=2.480,P=0.030) and power Doppler signal (t=2.681,P=0.020;t=5.482,P=0.000) were also reduced significantly after one month of intra-articular TNFR:Fc injection in elbow and ankle.Conclusion Intra-articular TNFR:Fc injection is an effective and safe treatment in RA patients with monoarthritis.Ultrasound may be an objective and valid method in evaluating the effect of intraarticular TNF inhibitor injection in RA patients.
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Objective:To investigate the effect of co-expression of sleeping beauty(SB)transposon and IL-10 mediated by adenovirus on the balance of Th17/Treg cells in the splenocytes of the non-obese diabetes(NOD)mice, and to illuminate the possible mechanism of IL-10 in the treatment of NOD mice.Methods:The splenocytes were extracted from spleen of the C57BL6 mice and cultured.The splenocytes were divided into control group,empty vector group and therapy group.The cells in control group didn't receive any treatment,the cells in empty vector group were co-infected with the adenovirus vector without IL-10 gene containing transposon sequence and the adenovirus vector without transposase,and the cells in therapy cells were co-infected with the adenovirus vector containing IL-10 gene and transposon sequence and the adenovirus vector with transposase.After 48 h of infection, the expression leves of IL-10 mRNA in the splenocytes of the mice in various groups were assessed by RT-PCR. The cells of above three groups were subcutaneously injected into popliteal space in right hind leg of the NOD mice in control group,empty vector group and therapy group;there were six mice in each group;once a week and six times.The mice were killed 4 weeks after injection,the expression levels of IL-10 in serum of the NOD mice in various groups were assessed by ELISA,and the proportions of CD4+IL-10+,CD4+IFN-γ+,Th17 and Treg cells in the splenocytes were detected by flow cytometry.Results:Compared with control group and empty vector group,the expression level of IL-10 mRNA in splenocytes of the C57BL6 mice in therapy group was increased (F=72.71,P<0.05);the expression level of IL-10 in serum of the NOD mice was increased(F=8.89,P<0.05);the proportions of CD4+IL-10+ cells and Treg cells were significantly increased(F=72.09,P<0.05;F=12.98,P<0.05);the proportion of Th17 cells was decreased(F=6.39,P<0.05).The proportion of CD4+IFN-γ+ cells had no significant differences between various groups(F=2.72,P>0.05).Conclusion:The co-expression of SB transposon and IL-10 can significantly increase the IL-10 level in serum of the NOD mice,increase the proportion of CD4+IL-10+ cells,decrease the proportion of Th17 cells and increase the proportion of Treg cells in the splenocytes,which can regulate the balance of Th1/Th2 and Th17/Treg cells and play a therapeutic effect in the NOD mice.
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Objective To explore the distribution characteristics and function of peripheral regulatory T cells (CD4+CD25+Foxp3+T cells) in patients with systemic lupus erythematosus (SLE).In addition,we analyzed the relationship between peripheral regulatory T cells and organ damage and the influence of different treatment regimens on them.Methods Two hundred and six SLE patients and 38 healthy volunteers were enrolled,which included 12 patients with untreated new-onset lupus,11 patients with drug withdrawal more than six months and 183 patients with treatments.Phenotypic and functional analysis of peripheral blood CD4+CD25+Foxp3+T cells were performed by flow cytometry.The correlations of CD4+CD25+Foxp3+ T cells with disease activity,organ involvement were analyzed.Thealtered frequency of CD4+CD25 +Foxp3+T cells under different treatment regimens was compared.Statistical Package form Soci-science (SPSS) 21.0 software was used for data analysis,Student's t test,one-way ANOVA,Mann-Whitney T test,Kruskal-Wallis test,Chi-square test,Simple linear correlation analysis was used.Results CD4 +CD25 +Foxp3 + T cells were significantly increased inactive SLE patients [1 1.9％ (9.3％,16.0％),mean difference =104.71,P＜0.01] and inactive SLE patients [11.0％(7.7％,14.7％),mean difference=86.10,P＜0.01] compared with healthy controls [6.1％(5.3％,7.4％)].CD4+CD25+Foxp3+T cellsshowed sign-ificantly positive correlations with SLEDAI-2K (r=0.191,P＜0.05),dsDNA (r=0.262,P＜0.05),ESR (r=0.208,P＜0.05) and lgG (r=0.163,P＜0.05),and significantly negatively correlated with complementC3 (r=-0.201,P＜0.05) and C4 (r=-0.227,P＜0.05).Compared with patients without organ damage (Occult lupus),the CD4+CD25+Foxp3+T cells were increased in SLE patients with organ damage,especially those with skin involvement [10.9％(7.8％,13.1％),mean difference=56.93,P＜0.05] and renal involvement [12.1％(9.1％,16.0％),mean difference=77.26,P＜0.05].The proportion of CD4+CD25+Foxp3+T cells had no significant difference between SLE patients with treatments and patients with untreated new-onset lupus.The expressions of CTLA-4 [(53±15)％,t=7.04,P＜0.01],GITR [(42±19)％,t=2.64,P＜0.01] and ICOS [(28±9)％,t=4.27,P＜0.01] on CD4+CD25+Foxp3+T cells were significantly lower in SLE patients than in healthy controls [CTLA-4 (71±4)％,GITR (53±10)％ and ICOS (41±6)％].IL-17 synthesized by CD4+CD25+Foxp3+T cells in SLE patients [3.0％(1.8％,3.9％)] was significantly higher than that in healthy controls [1.0％(0.7％,1.2％),Z=-4.40,P＜0.01].Conclusion The peripheral regulatory T cells are significantly increased in SLE patients and correlate with disease activity and organ damage.However,their inhibitory function is defective and they have more pro-inflammatory character-istics.
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Objective To analyze the clinical characteristics in elderly onset rheumatoid arthritis(RA) patients combined with interstitial lung disease(ILD).Methods Four hundred and four cases of elderly onset RA patients were summarized.They were divided into two groups according to whether combined with ILD.Its clinical manifestations,laboratory examinations and combined diseases were analyzed.Results (1)Male elderly patients with onset of RA were more likely to occur ILD than female(χ2=6.251,P=0.012).There was no significant difference in duration analysis of two groups(t=1.750,P=0.081).(2)The elderly onset patients in RA with knee pain were more likely to happen ILD(χ2=7.048,P=0.008),the difference was significant.And there was no significantly statistical difference in the shoulder joint pain(χ2=0.028,P=0.866),elbow pain(χ2=0.022,P=0.882),hand joint pain(χ2=2.041,P=0.153),hip pain(χ2=0.129,P=0.720),joint deformities(χ2=0.013,P=0.908),morning stiffness(χ2=0.000,P=0.984) and joints rheumatoid nodules(χ2=0.349,P=0.555) of two groups.(3)The elderly onset RA patients with a high level of serum RF were more likely to happen ILD(t=3.325,P=0.001),the difference was significant.And there was no significantly statistical difference in serum ANA antibodies(χ2=0.004,P=0.948),anti SSA(χ2=0.718,P=0.397),SSB antibody(χ2=0.638,P=0.424),AKA antibody(χ2=0.949,P=0.330),CCP antibody(χ2=0.500,P=0.479) and the level of ESR(t=0.582,P=0.561),CRP(t=0.381,P=0.703) and PLT(t=-1.246,P=0.213).(4)The elderly onset RA patients with ILD were more likely to appear osteoporosis(χ2=7.467,P=0.006),the difference was significant.And there was no significantly statistical difference in the occurrence of high blood pressure(χ2=0.403,P=0.526) and diabetes(χ2=0.180,P=0.671) in the two groups.Conclusion Male patients,the elderly onset RA patients with knee pain and associated with high level of serum RF more often occur with ILD.And the elderly onset RA patients with ILD are more likely to appear osteoporosis.
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Objective To investigate the clinical characteristics of patients with polymyositis(PM) and dermatomyositis (DM), and compare the differences of PM/DM to help the understanding of clinical diagnosis and treatment. Methods One hundred and forty-five hospitalized PM/DM patients from Department of Rheumatology of the First Affiliated Hospital of Xiˊan Jiaotong University were collected from May 2008 to December 2014, and the clinical manifestations, muscle enzymes, electromyogram, muscle biopsy, treatment outcome were retrospectively analyzed. Mann-Whitney U test and χ2 test were used for statistical analysis. Results The most common initial symptom of PM was muscle weakness, accounted for 51.2%, while rash was the initial presentation in most DM patients(43.1%). The incidence of interstitial lung disease (ILD) (62.7% vs 39.5%, χ2=11.009, P=0.001), and the elevation of CRP (48.9% vs 26.8%, χ2=10.272, P=0.001) were all higher in DM than PM, while the elevation of level of CK (85.4% vs 61.8%, U=-2.668, P=0.008) and CKMB (82.9%vs 41.2%, U=-3.303, P=0.001) were more common in PM compared with DM. The pathological study showed degeneration of muscle fiber, connective tissue hyperplasia in most PM patients, and perimysium atrophy, vacuoles degeneration, muscle bundles, perivascular inflammatory cell infiltration were observed in most DM patients. During the follow-up, the clinical remission rate was 57.5%, the relapse rate and the mortality rate was 7.5%and 31.1%respectively. The mortality rate was higher in DM than PM (34.6% vs 21.4%, χ2=4.861, P=0.027). Infection and tumors were the major causes of death, and the lung was the most common site of infection. Conclusion Differences in the clinical features, muscle enzymes, CRP level, pathology and the mortality rate between PM and DM are evident, while ILD, infection and the higher mortality rate are more common in DM than in PM.
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Objective To explore the clinical significance of dyslipidemia in patients with systemic lupus erythematosus (SLE).Methods By independent-samples t test,serum lipid level was compared between 326 SLE patients and 300 healthy controls.The total cholesterol (TC),triglyceride (TG),lowdensity lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels were partially compared in subgroups of SLE patients.The correlation of serum TC,TG,LDL-C and HDL-C with clinical manifestations and laboratory findings in SLE was analyzed by Pearson or Spearman correlation analysis.Results ①The serum levels of TC [(3.8±1.5) mmol/L],TG [(2.1±1.6) mmol/L] and LDL-C [(2.1±0.9) mmol/L] were significantly higher in SLE group than those of the control group [(3.4±0.6),(0.8±0.4),(1.9± 0.5) mmol/L],and the serum level of HDL-C [(1.2±0.9) mmol/L] was significantly lower in SLE group than that of the control group [(2.0±0.5) mmolFL] (t=4.953,P=0.000; t=14.569,P=0.000; t=3.204,P=0.001; t=-14.335,P=0.000].② The serum levels of TC [(4.0± 1.7) mmol/L],TG [(2.5± 1.7) mmol/L] and LDL-C [(2.2±1.0) mmol/L] were significantly higher in LN group than those of the non-LN group [(3.6±1.0),(1.6± 1.0),(1.9±0.7) mmol/L; t=2.646,P=0.009; t=6.292,P=0.000; t=3.261,P=0.001].③ The serum level of TG [(2.2±1.6) vs (1.8±1.4) mmol/L] was significantly higher in SLE patients with hypocomplementemia than that of the normal ones (t =2.098,P=0.038).The serum level of HDL-C [(1.1 ±0.4) vs (1.6± 1.7) mmol/L] was significantly lower in SLE patients with hypocomplementemia than that of the normal ones (t=-2.375,P=0.020).④ The serum level of TG [(2.3±1.7) vs (2.0±1.4) mmol/L] was significantly higher in anti-dsDNA antibody positive patients than that of negative ones (t=1.989,P=0.048).The serum level of HDL-C [(1.5± 0.4) vs (1.4±1.2) mmol/L] was significantly lower in anti-dsDNA antibody positive patients than that of negative ones (t=-2.979,P=0.003).⑤ The lipid level was correlated with the clinical manifestations and laboratory findings in SLE patients.Conclusion Dyslipidemia exists in patients with SLE and has close correlation with LN,hypocomplementemia and positive anti-dsDNA antibody.
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Objective To assess the disorders of glucose metabolism and insulin resistance in patients with rheumatoid arthritis (RA) and its relationship with disease activity.Methods One hundred and twenty-three RA patients along with 98 age and sex matched controls were studied.Seventy-five g oral glucose tolerance test was performed.The homeostasis model assessment of insulin resistance (HOMA-IR) and beta cell function (HOMA-β) were evaluated.Disease activity score (DAS28) was used to assess disease activity.According to their DAS28 values,patients were divided into high disease activity group and low to moderate disease activity group.Glucose tolerance and HOMA-IR were compared between the two groups.Parameters that reflects disease activity,such as CRP and ESR,as well as disease activity scores were compared between patients with T2DM or prediabetes and patients with normal glucose tolerance.The data was analyzed by t test,Pearson correlation analysis and chi-square test.Results The prevalence of T2DM [20.3％(25/123) vs 5.1％ (5/98),x2=10.774,P＜0.01] and prediabetes [39.0％ (48/123) vs 7.1％ (7/98),x2=29.657,P＜0.01] increased in RA patients compared to controls.RA patients had higher HOMA-IR (2.5±1.5 vs 0.8±0.4; t=5.185,P＜0.01) and lower HOMA-β (83±69 vs 192±85; t=3.768,P＜0.01) compared to controls.ESR [(55±30) mm/1 h vs (37±26) mm/1 h; t=3.159,P＜0.01],CRP [(40±23) mg/L vs (19±10) mg/L; t=3.628,P＜0.01] and DAS28 score (5.6±1.3 vs 4.8±1.2; t=2.923,P＜0.01) were higher in RA patients with T2DM or prediabetes than in RA patients with normal glucose tolerance.In RA patients,the HOMA-IR was significantly positively correlated with DAS28 (r=0.39,P＜0.01),ESR (r=0.54,P＜0.01)and CRP (r=0.20,P＜0.05).The HOMA-IR value and fasting insulin levels were higher in high disease activity patients (DAS28＞ 5.5) than in low-to-moderate disease activity patients (DAS28 ≤5.5) although fasting plasma glucose level did not differ significantly in these two groups.Conclusion The prevalence of T2DM and prediabetes increases in RA patients comparing to controls.RA patients have insulin resistance that is associated with disease activity and systemic inflammation.
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Objective To explore the relationship between cardiac involvement and laboratory indicators in patients with rheumatoid arthritis(RA). Methods Cardiac echocardiography and ECG performance of 184 patients with RA were analyzed retrospectively. Results Among the 184 patients with RA, the pulmonary hypertension detection rate was 8. 3%, valvular disease 38. 9%, arteriosclerosis 27. 8%, wall to reduce the exercise 13.9%, myocarditis 5.6% and pericardial effusion 5.6%, according to the echocardiography examinations;Sinus tachycardia was evidenced in 15. 22% patients, ST-T changes in 39. 13%, electric axis left side in 8. 70%, branch block in 13.04%, left ventricular hypertrophy in 4. 35%, atrial fibrillation in 4. 35%, premature in 8.70%, early repolarization syndrome in 2. 17% and electric-axis right side in 4. 35% patients by ECG examinations. The serum level of CRP (46. 77 ±5. 87) mg/L was significantly higher in RA patients with cardiac involvement than that in the non-cardiac involvement patientsm (28. 45 ±3. 21) mg/L (P ＜0.05) ;While the serum level of ESR,RF,IgG,IgA,IgM, PLT showed no statistically significant differences between the two groups (P ＞ 0.05); Within RA patients withcardiac involvement, the serum level of CRP showed no significant difference among different sub-groups , which were classified according to the echocardiography performance (P ＞ 0.05). Conclusions Cardiac involvement occurred frequently in patients with rheumatoid arthritis. The valvular disease, arteriosclerosis, reducing of the wall motion and pericardial effusion are the main manifestations by echocardiography examination; Sinus tachycardia, ST-T changes,branch block and premature beats are the main ECG abnormalities. The serum level of CRP is significantly higher in RA patients with cardiac involvement than that with non-cardiac involvement patients. The higher level of CRP in patients with RA may indicate the cardiac involvement presence.