Increased CCR4 expression on circulating CD4(+) T cells in ankylosing spondylitis, rheumatoid arthritis and systemic lupus erythematosus

Previous studies have suggested that CCR4 is particularly important in the selective recruitment of various subsets of leucocytes in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In this study, we examined the percentage of CD4(+)/CCR4(+) T cells within circulating lymphocytes in active ankylosing spondylitis (AS), RA and SLE patients. The clinical significance of CCR4 expression as well as possible associations between the expression and serum levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma and interleukin (IL)-10 were also examined. Our results showed that the percentage of CD4(+)/CCR4(+) T cells was significantly elevated in AS and RA patients as compared with normal controls. The percentage was also significantly higher in SLE patients who had received no treatment with glucocorticoids or cytotoxic drugs (untreated SLE) than that in controls. In addition, the percentage of CD4(+)/CCR4(+) T cells showed significant positive correlations with the Bath ankylosing spondylitis disease activity index (BASDAI) in AS and with the SLE disease activity index (SLEDAI) in untreated SLE. Of all the cytokines examined, the elevated serum IL-10 level was closely correlated with the percentage of CD4(+)/CCR4(+) T cells in AS, RA and untreated SLE. These results suggest that CCR4 may be crucial in the pathogenesis of AS, RA and SLE. The percentage of CD4(+)/CCR4(+) T cells can serve as a useful marker for the activity of AS and untreated SLE.     

DNA levels in circulating immune complexes decrease at severe SLE flares-correlation with complement component C1q.

The objective of this study was to investigate the relationship of DNA content in circulating immune complexes with disease course and activity in SLE. The DNA content in circulating immune complexes containing anti-DNA antibodies of IgG class was determined in serial samples from 28 patients with SLE by a quantitative immunochemical assay. The patients presented various active disease manifestations over 5-55 months. Disease activity (SLEDAI-score), drug treatment and ACR-criteria were recorded. Levels of anti-dsDNA, CRP, leukocytes, complement components C3, C4 and C1q were measured. Patients with severe flares and high SLEDAI scores had low Clq levels at onset of active disease manifestations. The patients with low C1q serum levels during flare (n=13) had significantly lower amounts of DNA in immune complexes than patients with normal Clq (P=0.001). Levels of DNA in immune complexes correlated with Clq at flares (r=0.62, P<0.0001) and correlated inversely with SLEDAI scores (r=-0.47, P=0.012). In conclusion, the low levels of DNA in circulating immune complexes found in severely ill SLE patients with concomitantly low serum concentrations of Clq prior to flares might be related to tissue deposition of immune complexes.     

The expression and significance of intracellular T helper cytokines in systemic lupus erythematosus

To analyze the Th1 and Th2 paradigm of peripheral T helper cells in patients with systemic lupus erythematosus (SLE). The intracellular Th1 and Th2 cytokines were analyzed in fresh blood T cells from 20 SLE patients who had not yet received any treatment. Th1 and Th2 cells were quantitated based on their intracellular cytokine content as assessed by flow cytometry. Cytokine expressions were correlated with clinical features, laboratory findings, and disease activities. There was no difference in the expression of intracellular IFN-y, or IL-4 between SLE patients and healthy controls. However, the IL-2 and IL-10 levels were significantly higher and lower respectively in the lupus patients than in the control group. In addition, patients with arthritis had higher IFN-gamma expression than patients without arthritis. Moreover, patients with serositis or CNS involvement had higher IL-4 expression than in patients without these manifestations. There was no correlation between the SLEDAI scores and the cytokine expression levels. However, patients with serum anti-ds DNA antibodies had higher IL-10 levels than in those without these antibodies. The present study demonstrates that a Th1 pattern of intracellular cytokines predominates in patients with SLE prior to treatment. The pattern of particular intracellular T cell cytokines may suggest specific clinical manifestations and disease progression of SLE.     

负性调控因子IRAKM 在系统性红斑狼疮免疫调节异常中的作用

目的:研究白介素-1 受体相关激酶-M(IRAKM)在系统性红斑狼疮(SLE)中的表达及其与免疫调节的关系。方法:将103 例SLE 患者根据其疾病活动度评分(SLEDAI)分为活动期组(55 例)和稳定期组(48 例),另选40 名体检健康者作为对照组;采用实时荧光定量PCR(RT-PCR)法检测3 组外周血单核细胞中IRAKM mRNA 的表达量,酶联免疫吸附法(ELISA)检测血清中抗ds-DNA 抗体、抗Sm 抗体水平,免疫散射比浊法测定血清补体C3、C4 水平;应用单因素方差分析法分析3 组各观察指标的差异,Pearson 或Spearman 分析IRAKM 与SLE 自身抗体及补体的相关性。结果:活动期组和稳定期组SLE 患者的IRAKM mRNA 表达量均明显低于对照组(P<0.05),且活动期组比稳定期组更低,差异有统计学意义(P<0.05);与对照组比,活动期组和稳定期组血清抗ds-DNA 抗体和抗Sm 抗体水平均明显升高(P<0.05),补体C3、C4 的水平均明显降低(P<0.05),且活动期组血清自身抗体和补体水平变化较稳定期组更显著(P<0.05);SLE 患者的IRAKM mRNA 表达量与抗ds-DNA 抗体和抗Sm 抗体水平呈负相关(P<0.05),与补体C3、C4 水平呈正相关(P<0.05)。结论:IRAKM 负性调控参与SLE的免疫调节过程,其表达水平与SLE 病情活动程度密切相关。     

The expression of PD-1 and level of CXCL10 in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is known tobe a chronic and complicated rheumatic diseasewith an autoimmune etiology.SLEis also a proto-type of autoimmune disease due to a substantialoverlapinits clinical symptoms withother autoim-mune diseases . The immune systemof SLElosesbalance of auto-tolerance ,in which lymphocytesare activated excessively,contributingto SLE de-velopment .It has been well established that effi-cient T cell-mediated immune responses requirenot only the TCR-mediat…     

系统性红斑狼疮患者外周血单个核细胞干扰素诱导基因IFIT1和IFIT4 mRNA表达水平的研究

为分析系统性红斑狼疮（SLE）患者外周血单个核细胞（PBMC）中两个干扰素 （IFN）诱导基因（IFIT1、IFIT4）的表达及其与SLE疾病活动度的相关性,运用实 时定量聚合酶链反应（RT-PCR）方法检测95例SLE患者与48名正常对照者的 IFIT1、IFIT4的mRNA表达水平,并且与抗ds-DNA抗体等指标比较,分析IFIT1、 IFIT4的mRNA表达水平以及与抗ds-DNA抗体、SLEDAI积分之间的相关性。结果 显示：①SLE组与正常对照组相比,IFIT1、IFIT4的mRNA表达显著增高 （P〈0.01）;SLE活动组与SLE缓解组比较,IFIT1、IFIT4的mRNA表达增高 （P〈0.05）;SLE组IFIT1、IFIT4的mRNA表达水平之间呈正相关（r〉0.5,P〈0.05） 。②抗ds-DNA抗体与IFIT1、IFIT4的mRNA表达水平及SLEDAI积分呈正相关 （r〉0.5,P〈0.05）。结论：SLE患者IFIT1、IFIT4的mRNA表达水平显著增高,并且 与SLEDAI积分呈显著正相关,IFIT1、IF-IT4的mRNA表达水平对SLE患者病情活 动程度的判断有较大价值,抑制这2个基因的表达可能为SLE的治疗提供新的靶 点。     

Increased serum IL-10 in lupus patients promotes apoptosis of T cell subsets via the caspase 8 pathway initiated by Fas signaling

We sought to investigate the expression of Fas and FasL on T cell surface and caspase 8 involvement in T cell apoptosis promoted by serum IL-10 in systemic lupus erythematosus(SLE) patients.Cells and sera were obtained from 35 SLE patients.Apoptosis of T cells in patients with SLE was increased and associated with the SLE disease activity index(SLEDAI).Elevated expression of Fas and FasL on T cell surface contributed to increased apoptosis of T cells.Increased IL-10 in the sera of SLE patients was capable of inducing Fas and FasL expression on CD4~+T cell surface,promoting apoptosis of this cell subset.Decreased IL-10 serum levels and low expression of Fas were found in 5 patients of the first follow-up group after 2-month treatment.In another group with one-year treatment,the SLEDAI declined to inactive scores.Serum IL-10 was decreased significantly,and expression of Fas and FasL on T cells was also reduced.Declined apoptosis was predominant only in CD4~+T cell subset.When sera with high level of IL-10 were used to culture PBMCs from healthy controls,activated caspase 8 was elevated in CD3~+T,CD4~+T and CD8~+T cells.The study showed that serum IL-10 induced apoptosis of T cell subsets via the caspase8 pathway initiated by Fas signaling.Increased apoptosis of T cells contributes to autoantigen burden,which is pathogenic in the development of SLE.     

The reduction of serum B-lymphocyte activating factor levels following quinacrine add-on therapy in systemic lupus erythematosus

B-Lymphocyte-activating factor (BAFF/BLyS) is a survival factor for B cells, belonging to the tumor necrosis ligand super family. Serum BAFF levels have been found to be elevated in patients with systemic lupus erythematosus (SLE). Neutralization of BAFF activity was suggested as an additional therapeutic approach in SLE. To determine the effect of add-on Quinacrine (Qn) treatment on serum BAFF levels and the effect of this treatment on SLE disease activity index (SLEDAI), antidsDNA and anticardiolipin (aCL) antibody levels, we treated 29 stable SLE patients, who were maintained on prednisolone and hydroxychloroquine and in some on azathioprine (AZT), with additional Qn (100 mg/d) with an aim to further reduce disease activity. SLEDAI, antidsDNA, aCL antibodies and serum BAFF levels were assessed before and 3 months after the addition of Qn. Three months following Qn initiation, a reduction in SLEDAI was noticed in 19/29 patients (mean 8.8 +/- 2.3 to 3.3 +/- 1.5, P = 0.009), followed by reduction or discontinuation of prednisolone in all patients and the discontinuation of AZT in five patients. Serum BAFF levels were significantly reduced in 8/12 patients (mean 6.3 +/- 0.5 to 3.0 +/- 0.56 ng/ml P = 0.0001). This reduction was found in correlation with a decrease in aCL titres. However, the decrease in SLEDAI scores and antidsDNA antibody titres was unrelated to the decrease in serum BAFF or aCL levels. We conclude that the addition of Qn to previous therapeutic regimens in active SLE is beneficial and seems to reduce SLEDAI scores, serum BAFF and aCL levels and therefore should be considered in many of our SLE patients before aggressive treatments are given.     

CD40在系统性红斑狼疮外周血淋巴细胞的表达

使用密度离心法分离SLE患者和正常人外周血单个核细胞 (PBMC ) ,采用流式细胞术检测B淋巴细胞白细胞分化抗原 4 0 (CD4 0 )的表达水平 ,进行SLE患者 (活动期和缓解期 )和正常人之间的比较 ;并进行B淋巴细胞CD4 0表达水平和血清抗dsDNA抗体水平及狼疮活动指数 (SLEDAI)的相关分析。结果表明 ,活动期SLE患者外周血B淋巴细胞比例 (% )和其表达CD4 0的比例 (% )均明显高于缓解期SLE患者和对照组 ,其表达CD4 0的平均荧光强度 (MFI)在活动期SLE患者最高 ,缓解期SLE患者稍低 ,对照组最低 ;相关分析结果表明 ,活动期SLE患者B淋巴细胞CD4 0的表达比例 (% )和强度 (MFI)均与血清抗dsDNA抗体及SLEDAI呈正相关 ,后两者呈高度相关 ;缓解期SLE患者B淋巴细胞表达CD4 0的强度 (MFI)和SLEDAI呈正相关。CD4 0在活动期SLE患者B淋巴细胞的表达增加 ,其水平与疾病活动度有关。     

Reduced anti-TNFalpha autoantibody levels coincide with flare in systemic lupus erythematosus

Deviating cytokine patterns, as a consequence of aberrant immunoregulation, is implicated to be of aetiopathogenetic importance in systemic lupus erythematosus (SLE). To evaluate the possibility of anti-cytokine autoantibody-mediated cytokine regulation/dysregulation, IgG class autoantibodies against cytokines (IL-1beta, IL-6, IL-10, TNFalpha and TGFbeta(1)) were analysed by enzyme-linked immunosorbent assay (ELISA) in serial serum samples from clinically well-characterized SLE patients and in normal human sera (NHS). Anti-TNFalpha autoantibody levels were lower in patients with active disease compared to inactive disease (P<0.001) as well as to NHS (P<0.001). The anti-TNFalpha antibody levels correlated inversely to the SLE disease activity index (SLEDAI) (r(2)=0.07, P<0.01), whereas anti-TGFbeta antibodies were raised in SLE and correlated positively to levels of complement factor C1q (r(2)=0.08, P<0.005). Generally raised anti-cytokine antibody levels and correlations to disease activity measures were found in one individual. Inverse correlations were found comparing SLEDAI scores and autoantibodies to TNFalpha (r(2)=0.92) and IL-6 (r(2)=0.86) and positive correlations were found between levels of anti-TNFalpha and C1q (r(2)=0.86) and C3 (r(2)=0.90). We show, for the first time, a coincidence between reduced anti-TNFalpha autoantibody levels and disease exacerbation in SLE, which is of interest regarding aetiopathogenesis and disease control.     

系统性红斑狼疮患者血清IL-10和IL-18的检测及意义

目的探讨系统性红斑狼疮（SLE）患者血清IL-10和IL-18的表达及其与疾病活动的关系。方法应用ELISA法检测104例SLE患者和100例健康体检者血清IL-10和IL-18的水平,其中SLE患者根据疾病活动性指数（SLEDAI）评分标准分为活动组（56例）和缓解组（48例）,比较各组结果的差异,并分析SLEDAI与IL-10和IL-18的相关性。结果 SLE组IL-10和IL-18水平分别为（18.25±3.66）、（582.61±65.28）pg/ml,明显高于对照组的（7.12±2.36）、（186.24±60.39）pg/ml,差异有统计学意义（P〈0.01）;SLE活动组IL-10和IL-18水平分别为（25.98±4.75）、（683.72±62.48）pg/ml,高于缓解组的（14.67±3.21）、（493.51±69.17）pg/ml,差异亦有统计学意义（P〈0.01）;SLE患者血清IL-10和IL-18水平与SLEDAI呈正相关（P〈0.05）。结论 IL-10和IL-18在SLE发病机制中发挥重要作用,而且与疾病活动性相关。     

SLE患者检测血清ANCA的临床价值

目的 探讨抗中性粒细胞胞浆抗体（ANCA）在系统性红斑狼疮（SLE）患者中检测的临床意义.方法 通过间接免疫荧光法（IIF）检测57例SLE患者血清中的ANCA,对ANCA阳性血清采用免疫斑点法检测抗髓过氧化物酶（MPO）和蛋白酶3（PR3）抗体;同时以35例正常健康者作为对照组.回顾性分析SLE临床表现和实验室检查结果,SLE患者以SLE disease activity index（SLEDAI）分组（SLEDAI≥10为疾病活动组、〈10为疾病非活动组）,分析ANCA与其的相关性.结果 SLE患者中ANCA 阳性率为22.8%,其中核周型（pANCA）阳性12例,阳性率为 21.1%,胞浆型（cANCA）1例,阳性率为 1.7%,靶抗原均为非MPO、PR3;ANCA阳性组与ANCA阴性组SLE活动性存在显著性差异（P〈0.05）,ANCA阳性组患者的补体C3的下降、血沉（ESR）的增高、抗dsDNA抗体的阳性以及皮肤血管炎和肾脏损伤与ANCA阴性组比较,差异有统计学意义（P〈0.05）.结论 ANCA在SLE中有一定阳性检出率,对疾病活动性判断有一定的临床价值.     

钾通道在系统性红斑狼疮T细胞中的作用研究

目的:研究SLE患者外周血活化T细胞中Kv1.3和IKCa1通道的表达情况,以及阻断Kv1.3通道后对SLE患者T细胞增殖的影响。方法:①病例选择:SLE患者33例,健康对照组12例;②分离外周血T细胞,采用抗CD3单克隆抗体刺激T细胞活化,培养72小时;③荧光实时定量RT-PCR检测SLE患者活化T细胞中Kv1.3和IKCa1通道的mRNA表达;④CCK-8法检测阻断Kv1.3通道对SLE患者T细胞增殖的影响;⑤应用统计软件SPSS17.0进行数据统计分析;对Kv1.3和IK-Ca1通道mRNA相对表达量与补体C3、C4、抗dsDNA抗体、SLEDAI积分及尿蛋白间进行相关性分析。结果:①SLE患者外周血T细胞活化后Kv1.3通道mRNA的表达与正常对照组相比明显增高(P<0.0001),IKCa1通道mRNA的表达与正常对照组相比降低(P=0.006),SLE患者Kv1.3及IKCa1 mRNA表达水平均与补体C3、C4、抗dsDNA抗体、SLEDAI积分及尿蛋白无相关性。②Kvl.3通道阻断剂ShK可明显抑制SLE患者外周血T细胞的增殖(P<0.001)。结论:Kv1.3通过是SLE患者TEM细胞活化的主要离子通道,Kv1.3通道可成为SLE免疫治疗的一个新起点。     

Elevated serum interleukin-15 levels in systemic lupus erythematosus.

Interleukin-15 (IL-15) has multiple biological properties, including the induction of other cytokine production and the inhibition of T cell apoptosis. Recently, IL-15 was reported to have a major role in synovial inflammation of rheumatoid arthritis, and that it provokes and amplifies the inflammatory process through the activation of TNF-alpha production. In systemic lupus erythematosus (SLE), the dysregulation of apoptosis and various cytokine production were observed and have been implicated in the pathogenesis of SLE. Thus, we tried to determine serum IL-15 levels in SLE patients and to assess the relationship among IL-15 levels, TNF-alpha levels and disease activity of SLE. Twenty SLE patients and 10 controls were studied. Paired serum samples were collected from all SLE patients at the time of presentation with active disease and at 4 weeks after institution of treatment. IL-15 levels were determined by ELISA and compared with the disease activity indices in SLE. The disease activity of SLE was measured using the SLE Disease Activity Index (SLEDAI) and laboratory parameters such as circulating immune complex (CIC), C3, C4, anti-DNA antibody, IgG, IgM, and IgA. The IL-15 levels in SLE patients were significantly higher than those of controls (5.38 +/- 4.89 vs. 1.04 +/- 1.26 pg/ml). However, elevated IL-15 levels did not correlate with the SLEDAI, nor did they correlate with other laboratory activity indices. The changes in serum IL-15 levels did not correlate with the changes in serum TNF-alpha in the disease course of SLE patients, whereas TNF-alpha reflected the changes in disease activity of SLE. Serum levels of IL-15 are elevated in SLE patients, but IL-15 did not correlate with the disease activity of SLE. TNF-alpha production in SLE patients was unlikely to be related with IL-15.     

Increased lipid and protein oxidation and lowered anti-oxidant defenses in systemic lupus erythematosus are associated with severity of illness,autoimmunity, increased adhesion molecules,and Th1 and Th17 immune shift

This study investigated nitro-oxidative stress in patients with systemic lupus erythematosus (SLE) in association with disease activity, immune-inflammatory biomarkers, and adhesion molecules. Two-hundred-four patients with SLE and 256 healthy volunteers were enrolled in this case-control study, which measured nitro-oxidative stress biomarkers, including lipid peroxides (LOOH), advanced oxidation protein products (AOPPs), nitric oxide metabolites (NO_x), sulfhydryl (?SH) groups, products of deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) oxidative degradation, and total radical-trapping anti-oxidant parameter (TRAP). Also measured were anti-nuclear antibodies (ANAs), antibodies against double-stranded DNA (dsDNA), plasma levels of diverse cytokines, C-reactive protein, and adhesion molecules. LOOH (p < 0.001) and AOPP (p < 0.001) were significantly higher, while TRAP was significantly lower (p < 0.001) in SLE patients than in controls. AOPP and LOOH were significantly and positively associated with SLE disease activity index (SLEDAI) scores, anti-nuclear antibodies, and antibodies against double-stranded DNA (anti-dsDNA) levels, while TRAP was significantly and inversely correlated with SLEDAI, ANA, and dsDNA antibody levels. There were significant positive associations between AOPP and LOOH and immune-inflammatory markers, indicating T helper (Th)-17 and Th1 bias and Th1 + Th17/Th2 ratio (p = 0.002 and p = 0.001, respectively). AOPP and LOOH (positively) and TRAP (inversely) were associated with adhesion molecule expression. A model predicting SLE was computed showing that, using LOOH, AOPP, NO_x, adhesion molecules, and body mass index, 94.2% of the patients were correctly classified with a specificity of 91.5%. Increased nitro-oxidative stress takes part in the (auto)immune pathophysiology of SLE and modulates severity of illness and adhesion molecule expression.     

系统性红斑狼疮患者的Th细胞亚群平衡失调的初步研究

为分析Th亚群平衡失调在系统性红斑狼疮 (SLE )发生发展中的变化特点 ,以ELISA法检测血清IL 10、IL 12水平 ,以细胞内细胞因子的流式细胞术检测SLE患者PBMC的不同Th细胞亚群分泌细胞因子的变化特点 ,应用三色荧光标记技术分析Th1/Th2细胞表型。结果显示 :SLE患者血清IL 10水平显著高于正常人 ,而IL 12呈低水平表达。SLE患者CD4 + IFN γ IL 10 + 细胞亚群百分率显著高于正常人 ,IFN γ+ IL 10 与IFN γ IL 10 + 细胞亚群的比值明显降低 ,IFN γ+ IL 10 + 双阳性的CD4 + T细胞亦显著增多。SLE患者的CD4 + CCR5 CCR3+ 细胞亚群百分率与正常人比较显著升高 ,CD4 + CCR5 + CCR3 细胞亚群与正常人比较 ,示发现有显著差异 ,CD4 + CCR5 + CCR3 /CD4 + CCR3+ CCR5 比值显著低于正常对照组。这些结果提示 :SLE高水平IL 10与IL 12的低水平表达呈负相关 ;患者体内分泌IL 10的Th细胞数增多 ;Th细胞表面趋化因子受体的表达提示SLE存在CCR5 CCR3+ 细胞亚群的优势活化、数量增多 ,CCR5 + CCR3 /CCR3+ CCR5 细胞比例失调 ,从而导致免疫网络平衡被破坏。     

Two systemic lupus erythematosus (SLE) global disease activity indexes--the SLE Disease Activity Index and the Systemic Lupus Activity Measure--demonstrate different correlations with activation of peripheral blood CD4+ T cells

Global disease activity measurement in systemic lupus erythematosus (SLE) patients is important for the clinical estimation and adjustment of therapy. By contrast, immune system activation plays a significant role in disease pathogenesis, with CD4+ lymphocytes acting as central cells in the immune response. We investigated which scale better correlates with immunologic changes in the blood of SLE patients, the SLE Disease Activity Index (SLEDAI) or the Systemic Lupus Activity Measure (SLAM) scale. Samples of peripheral blood were obtained from 45 SLE patients with different disease activity as assessed by the SLEDAI and the SLAM scales on the same day. We assessed the percentage of CD4+ T cells with activation-associated receptors: CD69, CD25int, CD95, HLA-DR, and CD4+ T cells with killing properties containing perforin and granzyme B. Our results indicated that the percentage of CD4+CD69+ and CD4+CD25(int) cells did not correlate with either the SLEDAI or the SLAM scale. Significant and positive correlations were observed between percentages of CD4+CD95+ and CD4+HLA-DR+ lymphocytes and SLE activity, but only when activity was measured using the SLAM scale, not with the SLEDAI scale. The percentage of CD4+perforin+ and CD4+granzyme B+ cells also strongly correlated with disease activity measured only with the SLAM scale. We conclude that the SLAM scale better reflects changes of immune system activity in SLE patients compared with the SLEDAI scale.     

系统性红斑狼疮患者血清泌乳素水平的检测及其临床意义

目的：探讨系统性红斑狼疮(SLE)患者血清泌乳素(PRL)水平检测的临床意义。方法：应用免疫放射量度分析法测定了75例SEE患者与25例健康人血清PRL水平。结果：SLE患者血清PRL水平明显高于正常对照组，且活动期升高更明显；高泌乳素血症(HPRL)发生率为40％，伴HPRL的患者肾损害发生率明显高于血清PRL正常者；血清PRL水平与SLEDM评分、抗ds-DNA抗体滴度倒数呈正相关，与C3呈负相关。结论：SLE患者血清PRL水平升高与病情活动相关，其检测可作为监测狼疮病情活动性的指标之一；血清PRL水平升高与肾脏损害相关，提示PRL可能在SLE肾损害中起作用。     

Inverse correlation between CD4+ regulatory T-cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus

CD4(+) CD25(+) regulatory T cells (Tregs) are critical in maintaining self-tolerance and preventing organ-specific autoimmunity. Their role in paediatric systemic lupus erythematosus (SLE), an autoimmune disease characterized by inappropriate regulation of hyperactivated B and T cells, has not been clearly defined. Using flow cytometry to determine cell populations and real-time polymerase chain reaction to assay mRNA expression for FOXP3, CTLA-4, and GITR, we characterized CD4(+) CD25(+) T cells in paediatric SLE patients and healthy subjects. The frequency of CD4(+) CD25(+) Tregs was significantly decreased in patients with active SLE compared with patients with inactive SLE and with controls (7.27% +/- 2.50%, 9.59% +/- 2.80% and 9.78% +/- 2.11%, respectively; P = 0.027 and P < 0.001, respectively), and was inversely correlated with disease activity, as assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000 scores (r = -0.59, P = 0.001) and serum anti-double-stranded DNA levels (r = -0.65, P < 0.001). Our preliminary investigations found elevated surface expression of GITR in CD4(+) CD25(+) T cells, elevated mRNA expression of CTLA-4 in CD4(+) T cells and higher amounts of mRNA expression for FOXP3 in CD4(+) cells in patients with active SLE compared with patients with inactive disease and controls. We demonstrated reduced CD4(+) CD25(+) Treg levels were inversely correlated with disease activity, indicating a defective Treg population in paediatric SLE patients. The differences in the expression of FOXP3, CTLA-4 and GITR imply the possible role of CD4(+) Tregs in the pathogenesis of SLE.