ABSTRACT
Objective In order to explore the role of autophagy in the development of systemic lupus erythematosus (SLE),we measured the expression of autophagy related gene microtubule-associated protein 1 light chain 3 (LC3),Atg5,Beclinl,Atg7 and the incidence of autophagy in T cells from patients with SLE.Methods The mRNA levels of LC3,Atg5,Beclinl,Atg7 in T cells from 67 SLE patients and 31 healthy individuals were detected by real-time quantitative polymerase chain reacton (qPCR) technique.Autophagy in T cells from 17 SLE patients and 11 healthy controls was also determined by flow cytometry (FACs).The correlation of Atg7 mRNA expression with clincal features was then analyzed.The differences between the two groups were tested by t-test and x2 tcst,all data were analyzed by statistical and service solutions (SPSS) 17.0 software.Results The mRNA levels of LC3 and Atg7 (ΔCT value) in SLE patients were obviously down-regulated as compared to healthy populations (P=0.010,P=0.002),paralleled with the decreased autophagy rate detected by flow cytometry in T cells of SLE patients [(3.7±1.9)％ vs (6.6±1.4)％,t=4.132,P=0.000].Also,the protein expression levels of LC3-Ⅱ in T cells of SLE patients (LC3-Ⅱ/GAPDH) was significantly lower than those in healthy controls (0.21±0.08 vs 0.34±0.11,t=1.846,P=0.047).Moreover,Atg7 mRNA expression levels were found to be negatively correlated to autophagy rate (r=-0.492,P=0.008).However,when comparing the clinical features of 24 SLE patients with decreased Atg7 mRNA expression (ΔCT value＞9.86) to 43 SLE patients with normal or high Atg7 mRNA expression (ΔCT value ＜9.86),increasing trend of incidence of arthritis,blood involvement and CNS was noted in patients with decreased Atg7 mRNA expression.However,there was a significant difference between the two groups in the incidence of renal involvement and anti-dsDNA antibody and SLEDAI (P=0.008,P=0.018,P=0.035).Conclusion The impaired autophagy resulted from down-regulated LC3 and Atg7 mRNA levels in T cells from SLE patients indicates that autophagy plays a role in mediating the occurrence and development of SLE,which might be through unable to clean harmful molecules effectively.
ABSTRACT
Objective In order to explore the effect of 25-(OH)D3 on monocyte chemoattratant protein (MCP)-1 expression from patients with system lupus erythematosus (SLE),we detected the level of active vitamin D and the expression of MCP-1 mRNA in patients with SLE,and analyzed the correlation between them.Methods The level of serum 25-(OH)D3 and mRNA expression of MCP-1 in 154 SLE patients and 31 healthy individuals were detected by enzyme-linked immuno sorbent assay (ELISA) and real time quanti-tative pol ymerase chain reaction (PCR) respectively.We also analyzed the correlation between serum 25-(OH)D3 level and the expression of MCP-1 mRNA,then analyzed the function of 25(OH)D3 on the regula-tion of MCP-1 mRNA expression in vitro.The differences between the two groups were tested by t-test and x2 test,multiple data were tested by one-way ANOVA and the correlation was analyzed by Pearson's correlation,all data were analyzed by statistical product and service solutions (SPSS) 17.0 software.Results The serum 25(OH)D3 levels in SLE group (20±11) ng/ml was significantly lower than normal control group (29±11) ng/ml (t=4.198,P＜0.01),and the ratio of the serum levels of vitamin D deficiency in SLE group were significantly higher than that of normal control group [55.8％(86/154) vs 22.6％(7/31),x2=11.421,P=0.001].The expression level of MCP-1 mRNA in PBMCs from the normal control group was significantly lower than the SLE group (1.14±0.27 vs 1.44± 0.31,t=3.277,P=0.001),serum 25(OH)D3 level and MCP-1 mRNA expression in patients with SLE PBMCs were significantly negatively correlated (r=-0.289,P＜0.01).Further study found that 25-(OH)D3 inhibited MCP-1 mRNA expression in PBMCs from SLE patients depending on the concentration.Conclusion The decreased 25-(OH)D3 level and up-regulated MCP-1 mRNA expression suggestthat MCP-1 may play an important role in SLE pathological process.
ABSTRACT
Objective Increasing evidence supports the involvement of autophagy in the etiopathology of autoimmune diseases.Systemic lupus erythematosus (SLE) is a potentially fatal autoimmune disease characterized by production of multiple autoantibodies through poorly understood mechanism.In order to explore the role of autophagy in the development of SLE,the expression of autophagy related gene microtubule-associated protein 1 light chain 3 (MAPLC3) in peripheral blood mononuclear cells (PBMCs) was measured in patients with SLE.Methods The mRNA levels of LC3 in PBMCs from 56 SLE patients and 45 healthy individuals were detected by real-time quantitative polymerase chain reaction (qPCR) technique.Autophagy in PBMCs was also determined by flow cytometry (FACs) in 20 SLE patients and 15 healthy controls.The correlation between LC3 mRNA expression and disease activity of SLE (SLEDAI) was then analyzed.Results The mRNA level of LC3 (RQ) in SLE patients was obviously downregulated compared with that in healthy population (1.30 ± 0.10 vs 1.35 ± 0.09; P =0.029),paralleled with the decreased autophagy rate detected by flow cytometry in PBMCs of SLE patients [(2.21 ± 1.07) ％ vs (9.91 ±4.01) ％ ;P =0.047].Moreover,LC3 mRNA expression level was negatively correlated with SLEDAI (r =-0.337,P =0.023).However,when the clinical features of 27 SLE patients with decreased LC3 mRNA expression (RQ ＜ 1.351) were compared with those of other 29 SLE patients with normal or high LC3 mRNA expression (RQ ＞ 1.351),increasing rates of arthritis,serositis,hematological abnormalities were noted in patients with decreased LC3 mRNA expression yet without statistically significance.However,there was a significant difference between two groups in the incidence of renal involvement (P =0.028).Conclusion The impaired autophagy due to dowrnregulated LC3 mRNA level in SLE patients indicates that autophagy plays a role in mediating the occurrence and development of SLE.
ABSTRACT
ObjectiveTo determine the distribution of vitamin D receptor (VDR) gene Apa Ⅰ and Bsm Ⅰ polymorphism in systemic lupus erythematosus (SLE) and the association with SLE in Chinese Han patients.MethodsGenomic DNA from 244 Chinese SLE patients and 162 sex and ethnically matched controls were typed for VDR Apa Ⅰand Bsm Ⅰpolymorphism combination by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Clinical characteristics were analyzed between different Apa ] and Bsm Ⅰ genotypes.ResultsThere was no significant difference between the distribution frequencies of allelic gene A and a in SLE patients and the controls,but the distribution frequency of genotypes heterozygote Aa in SLE patients was higher than that in the controls ( 38.9％ vs 22.2％,x2 =12.442,P =0.000).There was no significant difference between the distribution frequency of allelic gene and genotypes of Bsm Ⅰin SLE patients and the controls ( P ＞ 0.05 ).However,there was significant difference between the distribution frequencies of Apa Ⅰ and Bsm Ⅰ genotypes combination in SLE patients and the controls (x2 =18.226,P =0.006).The distribution frequency of genotypes Aa-bb in SLE patients was higher than that in the controls ( 32.4％ vs 17.9％,x2 =10.449 P =0.001 ),while the distribution frequency of genotypes Aa-bb in SLE patients was lower than that in the controls (30.3％ vs 42.0％,x2 =5.808,P =0.016). Furthermore,analyzing the effect of VDR Apa Ⅰand Bsm Ⅰ polymorphism combination to the symptoms of SLE,significant difference was observed in SLE patients carrying Aa-bb genotypes involved in serositis ( P =0.003 ),hematological system disorder ( P =0.021 ),and anti-Sm antibodies ( P =0.01 ) compared with other genotypes.ConclusionThere is significant association between Apa Ⅰ and Bsm Ⅰ gene polymorphism Aa-bb genotypes and the incidence of SLE in the Han population of China,and genotype Aa-bb is more involved in serositis,hematological system disorder and has a positive effect on production of antibodies.
ABSTRACT
Objective To investigate the existence and significance of circulating autoantibodies to thrombopoietin (TPO) in sera from patients with systemic lupus erythematosus (SLE).Methods Fifty-six consecutive patients with SLE,twenty patients with idiopathic thrombocytopenic purpura (ITP),and twenty normal individuals were involved in this study.The characteristics of all patients with SLE were analyzed.Antibodies to TPO were detected using an enzyme-linked immunosorbent assay (ELISA).For normal distribution count data,x2 test or Fisher exact test was used,t test was used for measurement data,and Wilcoxon's rank test for non-normally distributed data which was represented by M(Q).Results A higher frequency of antibodies to TPO were observed in SLE patients than those in healthy controls (39.3％ vs 0,x2=11.058,P=0.001).Moreover,anti-TPO antibodies were detected in 15 (57.7％) of 26 SLE patients with thrombocytopenia,compared with that in 7 (23.3％,x2=6.894,P=0.009) of 30 patients without thrombocytopenia.Furthermore,the patients with antibodies to TPO exhibited more severe thrombocytopenia (t=3.010,P=0.004).Finally,anti-TPO antibodies seemed more likely to occur in patients with arthritis (x2=5.959,P=0.015),anti-dsDNA antibodies (x2=5.959,P=0.015).Conclusion The high incidence of antibodies to TPO in SLE patients with thrombocytopenia suggests that anti-TPO antibodies might play a vital role in SLE patients developing thrombocytopenia.Thus,there might be a clinical value by detecting anti-TPO antibodies in SLE patients with thrombocytopenia.
ABSTRACT
Objective To determine the distribution of vitamin D receptor(VDR)gene FokI polymorphism in systemic lupus erythematosus(SLE)and the association with SLE in Chinese Han patients. Methods Genomic DNA from 271 Chinese SLE patients and 130 sex and ethnically matched controls were typed for VDR FokI polymorphism by polymerase chain reaction restriction fragment length polymorphism(PCRRFLP). Clinical characteristics were analyzed between different FokI genotypes. ResuIts Fokl allelic frequencies were not in Hardy-Weinberg equilibrium(χ2=7.288, P=0.026 for the control group and χ2=7.883, P=0.019 for the SLE patient group). The distribution frequencies of allelic gene F and f were 48.8% and 51.2% in the controls respectively, 60.9% and 39.1%(χ2=10.39, P=0.001)in the SLE patients respectively. The relative risk of allelic gene F developing to SLE was 1.630(95%CI=1.210～1.196, χ2=10.39, P=0.001). The distribution frequencies of genotypes homozygote FF, heterozygote Ff and homozygote ff were 25.4%, 46.9%,and 27.7% in the controls respectively; 42.8%(χ2=11.417, P=0.001), 36.2%(χ2=4.251, P=0.039)and 21.0% (χ2=2.187, P=0.139)in SLE respectively. The relative risk of homozygote FF and heterozygote Ff genotypes was 2.200(95%CI=1.385～3.493, χ2=11.417, P=0.001)and 0.641(95%CI=0.419～0.979, χ2=4.251, P=0.039)respectively. Furthermore, no significant difference was observed in SLE patients carrying different FokI genotypes in SLE disease activity index(SLEDAI)(P=0.382), symptoms and signs, while significant difference was observed in SLE patients carrying heterozygote Ff genotypes involved in serositis(P=0.001). Elevated frequencies of heterozygote Ff genotypes were observed in patients with anti-dsDNA antibody, anti-Sm antibody and anti-histone antibody respectively(P=0.001, P=0.047, P=0.001 respectively). However, the incidence rate of malar rash was lower than other genotypes in heterozygote Ff genotypes(P=0.005).Conclusion There is association between the VDR gene FokI polymorphism and the susceptibility to systemic lupus erythematosus in Han population of southern China. Allelic gene F, homozygote FF and heterozygote Ff genotypes increase the susceptibility to systemic lupus erythematosus. Otherwise, heterozygote Ff genotype is more frequently involved in serositis and generates anfi-dsDNA antibody, anti-Sm antibody and anti-Histone antibody.
ABSTRACT
Objective To determine plasma soluble HLA-G (sHLA-G) levels in patients with systemic lupus erythematosus (SLE),and to analyze its association with the possibility of organs or systems involvement in lupus patients.Methods Plasma samples were collected from 96 SLE patients and 74 healthy controls,and sHLA-G levels were determined by enzyme-linked immunosorbent assay.The sHLA-G levels in SLE patients and healthy controls were compared with students't-test.The difiefence of clinical and seroimmunological data among the SLE patients was assessed by chi-square test or students't-test.A value of P<0.05 was considered to be significant.Results Plasma concentration of sHLA-G was significanto higher in SLE patients than that in healthy controls[(230±192)U/ml vs(118±38)U/ml,P=0.0001].No relationship between plasma sHLA-G levels and SLE disease activity index(SLEDAI)was found(r=0.157,P=0.141).However,the patients with increased levels of sHLA-G had more severe disease activity (11±5 vs 8±5,P=0.027) and more central nervous system (CNS) involvement (24.2% vs 4.8%,P=0.007) in comparison with patients with normal plasma levels of sHLA-G.Conclusion The increased production sHLA-G,paralleled with more severe disease activity and higher CNS involvement,indicates that sHLA-G may play an important role in the pathogenesis of SLE.
ABSTRACT
Objective To study clinical characteristics in patients of systemic lupus erythematosus (SLE)with cardiac involvement and to assess relevant risk factors contributed to it.Methods Totally,239 patients of SLE were evaluated by cardiogram,echocardiogram and serologic examinations,and those with cardiac involvement were compared to those without it by clinical and laboratory data.Results There were 114 of 239(47.7%)SEE patients with cardiac abnormalities,of whom only 31(27.2%)had cardiac symptoms,including 44 cases(38.6%)with hydropericardium,32(28.1%)with myocardial damage,14 (12.3%)with cardiac valvular lesions,19(16.7%)with cardiac block,and 13 with other cardiac damages.No significant difference in age,gender,course of disease,SLE activity index(SEEDAI)scores,serum levels of auto-antibodies and complement(C3),and so on,were found between 114 SLE patients with cardiac abnormalities and 64 without it,who were:randomly selected from 125 patients of SEE without cardiac damage.But,patients of SLE complicated with pericarditis or myocardial lesions had higher SLEDAI scores and lower serum level of C3 than those without cardiac lesions(both P＜0.05),and relatively longer course of disease was found in those with valvular heart disease.Conclusions Cardiac damage was common in patients with SLE,but most of whom were asymptomatic,and only those with severe and active illness tended to develop pericarditis and myocardial damage and those with longer course were liable to have valvular heart disease.
ABSTRACT
0.05).However,the patients with increased levels of sHLA-G had higher incidence of central nervous system involvement(P=0.007) and more severe disease activity(P=0.027) in comparison with patients with normal plasma sHLA-G levels.Finally,the expression of plasma sHLA-G was not influenced by the treatment with glucocorticoids,immunosuppressive agents or antimalarials.Conclusion The increased production of sHLA-G indicates that sHLA-G may play an important role in the pathogenesis of SLE.The expression of sHLA-G may be associated with disease activity and severity of lupus patients,but be independence of HLA-G 14bp ins/del polymorphism and drug treatment.