Increased expression of CD40 ligand by peripheral blood mononuclear cells in patients with systemic lupus erythematosus

AIM:To investigate expression and function of CD40 ligand by peripheral blood mononuclear cells (PBMCs) in patients with systemic lupus erythematosus (SLE).METHODS:Expression of CD40 ligand by PBMCs in patients with SLE and control were examined by flow cytometric analysis before and after stimulated by phytohemagglutinin(PHA)and depressed by Dexamethasone(Dex). The correlation between expression of CD40 ligand and SLE activity index(SLEDAI) was analysed in patients with SLE.RESULTS:The expression of CD40 ligand by PBMCs in patients with active SLE was higher than that in patients with inactive SLE and control. Though the expression of CD40 ligang by PBMCs could be stimulated by PHA in three groups, it was the highest in patients with active SLE. Dex depressed the expression of CD40 ligand by PBMCs significantly in patients with SLE, but not in control. There was high positive correlation between expression of CD40 ligand and SLEDAI in patients with active and inactive SLE.CONCLUSION:Increased expression of CD40L by PBMCs in patients with SLE may play an important role in pathogenesis of SLE.     

Association of polymorphism of Fc receptor γ chain gene at position-29 in promoter with the susceptibility to systemic lupus erythematosus in southern Chinese

AIM:To detect the association between the polymorphism of Fc receptor γ chain gene at position-29 in promoter and systemic lupus erythematosus(SLE).METHODS:The genotypes at position -29 in promoter of Fc receptor γ chain gene were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 180 patients with SLE and 140 ethnically matched controls in southern China.RESULTS:The frequencies of TT genotype(33.3%) and T allele (54.4%) at position -29 in patients with SLE were significantly higher than those in controls (17.2% and 42.9%, respectively), whereas, the frequencies of GG genotype (24.4%) and G allele (45.6%) in patients with SLE were remarkably lower than those in controls (31.4% and 57.1%, respectively) (P＜0.05). The TT genotype and T allele at position -29 were not associated with lupus nephritis in SLE patients (P＞0.05).CONCLUSION:Our results indicate that the T allele at position -29 in promoter of Fc receptor gene probably contributes to the susceptibility to SLE, but does not play a role in the occurrence of lupus nephritis.     

Expression and role of CD134 and NF-κB in renal tissue of lupus nephritis

AIM:To investigate the role of CD134 (OX40) and NF-κB in the pathogenesis of lupus nephritis (LN).METHODS:Renal in situ CD134 and NF-κB expression were examined in 40 biopsy specimens from LN patients by immunohistochemistry and microwave-based immunohistochemistry, respectively. The relationship between expression of CD134 and NF-κB was analyzed.RESULTS:The expression of glomerular and tubular CD134 and NF-κB in LN were higher than that in normal control, especially in class Ⅳ LN, where there was intense staining of endothelial cell, distal tubules, and interstitial mononuclear cell. The CD134 expression of glomerular and tubular was closely related to NF-κB expression, respectively (r=0.5542, P＜0.05;r=0.6279, P＜0.05). CONCLUSIONS:The abnormal expression of costimulatory molecule CD134 was well evidenced in LN. Strong expression of renal in situ NF-κB was likely mediated by CD134 signal pathway, which may play an important role in the pathogenesis of LN.     

IL-33/ST2 axis in systemic lupus erythematosus in relation to chronic kidney injury and disease activity

AIM: To elucidate the association between chronic kidney injury and interleukin-33 (IL-33; an alarmin)/suppression of tumorigencity 2 (ST2) in patients with systemic lupus erythematosus (SLE).METHODS: Serum levels of IL-33 and soluble ST2 (sST2) were assessed by ELISA in 50 SLE patients and 30 healthy controls (HC).RESULTS: The levels of IL-33 and sST2, and IL-33/sST2 ratio were significantly higher in SLE patients than those in the HC. The IL-33 and sST2 levels were positively associated with SLE disease activity index (SLEDAI), erythrocyte sedimentation rate (ESR), proteinuria and triglyceride, but negatively associated with complement C3. IL-33/sST2 ratio was positively associated with SLEDAI and estimated glomerular filtration rate (eGFR). Independent explanatory variables associated with high IL-33/sST2 included chronic kidney disease (CKD) staging and albumin (R²=0.442), especially CKD staging.CONCLUSION: Elevated serum sST2 and IL-33 levels in SLE patients are correlated with disease activity and risk factors of kidney injury. IL-33/sST2 ratio may serve as a potential biomarker for chronic kidney injury in SLE patients.     

Serum auto antibodies and clinical/pathological features in German shepherd dogs with a lupuslike syndrome

This study presents 8 dogs of German Shepherd breed (6 males, 2 females, 2-5 years of age at onset of the disease) with a lupus like syndrome characterized by febrile polyarthritis, wasting, nephropathy, cutaneous lesions and high positive titres of ANA (antinuclear antibodies) of speckled type. The serum autoantibodies were further characterized by double immunodiffusion against ENA (extractable nuclear antigen), ELISA for Histone antibodies (Histon fraction H-24A and H-3S), indirect IF on rat-liver sections, non treated and RNase/DNase digested sections for DNP/RNP antibodies, and smears of a hemoflagellate C. luciliae for antibodies vs doubbel strained DNA, (dsDNA). Thus, the high ANA titres in these dogs represent varying types of autoantibodies against nucleoproteins of both DNA and RNA nature, associated histone antigens and non-histone antibodies (RNA and Sm) as well. Rheumatoid Factor titres in serum from these dogs were low or negative. Immunoglobulin deposits at dermo-epidermal junctions were demonstrated in some of the dogs with hyperkeratotic skin lesions. High concentration of serum-IgG was a constant finding in combination with anemia and in most cases leukopenia probably related to the chronic inflammatory process in these animals. Autoimmune hemolytic anemia (AIHA) or thrombocytopenia was not detected in these dogs.     

The role of TF-1 cell apoptosis-related gene 19 in systemic lupus erythematosus

AIM:To clarify the role of new apoptosis-related gene, TF-1 cell apoptosis-related gene 19(TFAR19), in the pathogenesis of systemic lupus erythematosis (SLE) and the relationship between TFAR19 and SLE.METHODS:DNA Ladder detection, Western blotting, immunological fluorescence method, ELISA and so on were used to test if ultraviolet B(UVB) could induce HaCaT cell apoptosis and TFAR19 expression.RESULTS:HaCaT cell apoptosis could be detected after 24 hours of 30 mj/cm² UVB irradiation. Also, we found that in active SLE patients, the TFAR19 antibody was increased, but not significant compared to the normal control.CONCLUSION:TFAR 19 is involved in the process of UVB induced ketatinocyte line HaCaT apoptosis and SLE pathogenesis.     

SLE患者CD4+CD25+调节性T细胞及Foxp3基因表达的研究

目的:研究系统性红斑狼疮(SLE)患者外周血CD 4 CD 25 调节性T细胞及Foxp3基因的表达水平,了解它们在SLE发病机制中的作用。方法:分别收集25例SLE患者(SLE组)及健康人(对照组)外周抗凝静脉血,分离纯化T淋巴细胞。PE标记抗CD 4单抗,F ITC标记的抗CD 25单抗,作双色流式细胞术,分析SLE患者外周血CD 4 CD 25 调节性T细胞百分率,RT-PCR检测T细胞Foxp3 mRNA表达。结果:SLE组外周血CD 4 T、CD 4 CD 25 T细胞百分率及T细胞Foxp3 mRNA水平均低于对照组(P<0.01),并且CD 4 CD 25 T细胞百分率与Foxp3mRNA水平呈依赖关系(P<0.01)。结论:SLE患者外周血存在细胞免疫功能失调,CD 4 CD 25 调节性T细胞数量减少和Foxp3mRNA表达下调可能与SLE的免疫学发病机制有关。     

Clinical significance of elevated serum interleukin 15 in patients with active lupus nephritis

AIM: To detect interleukin 15 (IL-15) levels in peripheral blood from patients with active lupus nephritis and investigate its clinical significance. METHODS: IL-15 level was determined by enzyme linked immunosorbent assay (ELISA). The peripheral blood mononuclear cells (PBMCs) were isolated with grads density abaxiality. The inhibitory effects of dexamethasone on production of IL-15, IgG and anti-dsDNA antibody in cultured PBMCs from LN patients were also investigated. RESULTS: (1) Serum IL-15 level in LN patients was significantly higher than that in normal controls (P<0.01). Serum IL-15 level in active LN patients was significantly higher than that in remised patients (P<0.05). (2) Serum IL-15 level was positively correlated with SLEDAI, anti-dsDNA antibody and 24 h urine protein excretion in active LN patients. (3) Serum IL-15 level was significantly reduced in LN patients treated with combination of cyclophosphamide (CTX) and steroid for 12 weeks. (4) Secretion of IL-15, IgG and dsDNA antibody in cultured PBMCs from active LN patients was significantly higher than that in normal control group, and IL-15 level in supernatant of cultured PBMCs from active LN patients was positively correlated with IgG and dsDNA antibody. Dexamethasone inhibited the secretion of IL-15, IgG and dsDNA antibody in cultured PBMCs from LN patients. CONCLUSION: Serum IL-15 level in patients with active lupus nephritis is significantly elevated, suggesting that IL-15 may be involved in the pathophysiological process of LN. IL-15 may be used as an index to assess the activity of LN.     

Association of S100B polymorphisms with systemic lupus erythematosus in Guangxi population

AIM: To explore the association of rs9984765, rs2839356 and rs2186358 polymorphisms in S100B gene with the susceptibility to systemic lupus erythematosus (SLE). METHODS: SLE patients (n=313) and age-and sex-matched healthy controls (n=396) were recruited in this study. The genotypes of the 3 sites were determined by single-base extension PCR (SBE-PCR) and DNA sequencing. RESULTS: No difference between the SLE patients and controls in the genotype and allele frequencies of rs9984765 and rs2186358 was observed. However, the frequency distribution of rs2839356 C allele was significantly different in the 2 groups (P=0.040). Stratification analysis showed that the frequency of rs2839356 C allele was higher in the patients with neurologic disorder than the patients without neurologic disorder (P=0.023).CONCLUSION: S100B gene rs9984765 and rs2186358 polymorphisms may not contribute to the susceptibility of SLE in Guangxi population. The rs2839356 C allele might be correlated with the SLE patients with neurologic disorder.     

犀角地黄汤加减联合血浆置换治疗急重型系统性红斑狼疮的疗效与机制研究

目的 探讨犀角地黄汤加减联合血浆置换（PE）治疗急重型系统性红斑狼疮（SLE）的疗效及作用机制。方法 纳入我院180例SLE患者,随机数字表法分为A、B、C三组。A组采取环磷酰胺冲击治疗、B组采取PE治疗,C组采取PE联合犀角地黄汤。比较三组治疗前后的症状评分、SLEDAI评分、补体C₃、血沉（ESR）、抗ds-DNA抗体、血清肌酐（Scr）、血清胱抑素（CsyC）、谷草转氨酶（AST）、谷丙转氨酶（ALT）、24 h尿蛋白、人干扰素-r（IFN-r）、白介素-10（IL-10）、BAFF因子,统计3组治疗总有效率及不良反应发生率。结果 B、C组治疗后各观察点的症状评分、SLEDAI评分、ESR、ds-DNA抗体、24 h尿蛋白、Scr、CsyC、AST、ALT、血清BAFF均低于A组（P<0.05）。C组治疗后各观察点的IFN-r^- IL-10⁺与IFN-r⁺ IL-10⁺亚群所占百分率低于A、B组（P<0.05）。B、C组治疗后各观察点的C₃高于A组（P<0.05）。B组与C组治疗总有效率为分别为90.0%、93.3%,均高于A组的71.7%（P<0.05）。C组不良反应发生率为10.0%,低于A组与B组（P<0.05,P<0.01）。结论 PE可去除血浆中有害成分、抑制炎症反应,联合犀角地黄汤可进一步扶助正气、解毒化瘀,改善机体免疫功能,达到增效减毒目的,效果更理想。