白细胞介素6在狼疮性肾炎患者小管间质的表达及其意义

探讨白细胞介素6(IL-6)在狼疮性小管间质病变中的作用。方法 采用ELISA方法与原位分子杂交技术(后者结合IBAS计算机图像分析系统),分别检测42例活动期狼疮性肾炎(LN)患者尿IL-6浓度与其中的15例肾小管间质IL-6mRNA水平。结果 42例活动期LN患者有36例尿IL-6>5pg/mg·cr,其增高程度与尿β_2-m及NAG活性水平呈显著正相关;其中15例肾组织切片中,肾小管间质均有IL-6mRNA表达,并且小管间质病变愈严重,其表达量愈高,而健康肾组织小管间质几无IL-6mRNA表达。结论 LN患者活动期尿IL-6浓度异常增高与肾小管间质IL-6mRNA异常表达有关,提示IL-6在狼疮性小管间质损害过程中可能具有重要作用。     

狼疮肾炎患者血清和尿白细胞介素-18水平检测及其临床意义

目的：检测狼疮肾炎(LN)患外周血清和尿液白细胞介素—18(IL—18)水平并探讨其临尿意义。方法：血清和尿液IL-18含量采用酶联免疫吸附方法(ELISA)。结果：LN组血清IL—18水平显高于正常对照组(P＜0、01)，活动期LN血清IL—18水平显高于缓解期患(P＜0．01)3LN组尿IL—18水平显高于正常对照组(P＜0．05)，活动期LN患尿IL—18水平显高于缓解期患(P＜0．05)。LN患血清IL—18水平与SLEDAI、抗dsDNA抗体成正相关关系，与补体C3呈负相关关系，而与血白蛋白、血肌酐无相关关系；活动期LN患尿IL—18水平与狼疮肾组织活动性指数(AI)、24h尿蛋白排泄量均呈正相关关系。结论：LN血清和尿IL—18水平显增高，IL—18可能在LN的病理生理过程中起重要作用。LN血清和尿IL—18水平均与狼疮病情活动密切相关，可作为判断狼疮疾病活动性的候选参考指标。     

Effect of human anti-DNA antibodies on proximal renal tubular epithelial cell cytokine expression: implications on tubulointerstitial inflammation in lupus nephritis

This study aimed to investigate the effects of human anti-DNA antibodies (Ab) from patients with lupus on renal proximal tubular epithelial cells (PTEC), focusing on alterations in cell morphology and proinflammatory cytokine synthesis. Immunohistochemistry showed increased tubulointerstitial IL-6 expression and IgG deposition in renal biopsies from patients with diffuse proliferative lupus nephritis, not observed in controls or membranous lupus nephritis, which correlated with the severity of inflammatory cell infiltration. Sera from patients with lupus nephritis contained IgG that bound to cultured PTEC. Such binding increased with disease activity and correlated with the level of anti-DNA Ab. Incubation of PTEC with anti-DNA Ab that were isolated during active (active Ab) or inactive (inactive Ab) disease induced IL-6 synthesis, both apically and from the basolateral aspect. This was accompanied by altered cell morphology, increased cell proliferation (P < 0.05), and lactate dehydrogenase release (P < 0.05). The binding of inactive Ab and active Ab to PTEC resulted in differential and sequential upregulation of TNF-alpha, IL-1beta, and IL-6 secretion (P < 0.05). Early induction of TNF-alpha was observed with active Ab; the two then acted synergistically to induce IL-6 secretion. Exposure of PTEC to inactive Ab was associated with modest induction of TNF-alpha, which was not involved in downstream induction of other proinflammatory peptides. These data suggest distinct immunopathogenetic mechanisms during disease flare or remission. Conditioned media from human mesangial cells acted synergistically with anti-DNA Ab to induce cytokine secretion in PTEC. Results from these studies underscore the pivotal role of PTEC in the pathogenesis of tubulointerstitial inflammation and fibrosis in lupus nephritis.     

Relationship of abnormal Tamm-Horsfall glycoprotein localization to renal morphology and function

Tamm-Horsfall glycoprotein (TH) distribution was studied using a biotin-avidin immunoperoxidase technique in renal biopsies from 166 consecutive patients and 8 normal kidneys. Tubulointerstitial damage was independently assessed and graded. In 109 patients TH antibodies were measured by ELISA and in 30 of these urinary TH and beta 2-microglobulin excretions were measured by radioimmunoassay. In 124 biopsies only distal tubular epithelium and casts were stained. Glomerular space (8) or interstitial (34) deposits were seen in 42 biopsies; 16/68 with glomerulonephritis, 4/14 with systemic vasculitis, 12/33 with chronic interstitial nephritis, 1/8 with acute interstitial nephritis, 9/43 with other nephropathies. There was no correlation between TH distribution and the degree of tubulointerstitial damage (p greater than 0.5), urinary TH excretion (p greater than 0.05), urinary beta 2-microglobulin excretion (p greater than 0.05), glomerular filtration rate, urinary concentrating ability, or the incidence of pyuria. TH antibodies did not correlate with TH distribution (p greater than 0.5) or the degree of tubulointerstitial damage. Abnormal TH distribution showed no statistical relationship to the degree of tubulointerstitial damage, changes in renal function or levels of TH antibodies.     

Association of serum renalase with disease activity in lupus nephritis

Objective To investigate the relationship between serum renalase and disease activity in lupus nephritis (LN). Methods Total of 70 patients with LN and 35 healthy volunteers admitted in Renji Hospital of Shanghai Jiao Tong University from March 2012 to March 2013 were enrolled in the study. LN patients were classified into two groups according to their systemic lupus erythematosus disease activity index (SLEDAI) scores: patients with SELDAI score lower than 8 were defined as inactive LN while others were defined as active LN. Serum samples were collected after an overnight fast and serum renalase level was determined by ELISA. Twenty active LN patients were followed up for six-months, and serum renalase was also determined before and after treatment. The differences in serum renalase level between LN patients and healthy controls were assessed, as well as the association of serum renalase with disease activity in LN. Results In 70 LN patients, 35 were classified active LN while others were inactive LN. Serum renalase level was significantly higher in LN patients than than in healthy controls (P﹤0.01). Moreover, active LN patients had higher serum renalase level compared to patients with inactive LN (P﹤0.01). Active LN patients had higher 24-hour urine protein excretion, erythrocyte sedimentation rate and anti-dsDNA antibody titers than inactive LN patients. Serum albumin was lower in inactive LN patients compared to active LN patients. There were no differences in gender, age, blood pressure and C-reactive protein between the two groups. Serum renalase levels were positively correlated with SLEDAI, 24-hour urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.894 with a cutoff value of 66.67 mg/L. Logistic regression showed that serum renalase (OR=1.078, 95%CI 1.031-1.120, P=0.001) and complement C3 (OR=0.022, 95%CI 0.002-0.326, P=0.005) is independent indicators for disease activity in LN. Conclusions Serum renalase level was correlated with disease activity in LN. Serum renalase may serve as a potential indicator for disease activity in LN.     

Serum levels of IL-1 beta,TNF-alpha,IL-8, and acute phase proteins in seronegative spondyloarthropathies

OBJECTIVES: Some immunological abnormalities have been described in seronegative spondyloarthropathies (SpA). The aim of this study is to determine the serum levels of IL-1beta, TNF-alpha and IL-8, which are proinflammatory cytokines in active and inactive patients with SpA, to compare the results with those of controls and to investigate a relationship with clinical activity and acute phase proteins. METHODS: Forty-two patients (34 males and eight females) and 22 healthy controls (17 M and 5 F) were included in the study. All patients fulfilled Amor criteria for the classification of SpA. Among patients 23 had active and 19 had inactive disease. IL-1beta, TNF-alpha and IL-8 were determined by enzyme-linked immunosorbent assay ( ELISA), acute phase proteins were measured by nephelometric assay. RESULTS: There was no statistically significant difference between mean IL-1beta levels of patient groups and controls. Serum mean TNF-a levels in active and inactive patients were significantly increased as compared to that in the controls (P < 0.05, P < 0.05, respectively). Serum mean IL-8 levels in active patients was significantly increased as compared to that in the controls and in inactive patients (P < 0.01, P < 0.01, respectively). High serum IL-8 levels correlated well with C-reactive protein and haptoglobulin, but there was no correlation between IL-1beta or TNF-alpha levels and acute phase proteins such as C-reactive protein, alpha-1 acid glycoprotein, alpha-1 antitrypsin and haptoglobulin. CONCLUSIONS: These results suggest that serum IL-8 may reflect clinical activity of the disease and may be helpful for monitoring patients with SpA.     

Glomerular and tubulointerstitial miR-638, miR-198 and miR-146a expression in lupus nephritis

Aim: MicroRNAs (miRNAs) play important roles in the pathogenesis of autoimmune diseases. We studied the intra‐renal expression of miRNA targets that were reported to be differentially expressed in peripheral blood or urine between lupus nephritis (LN) patients and normal controls. Methods: We quantified the expression of in glomerulus and tubulointerstitium of miR‐146a, miR‐155, miR‐198 miR‐638 and miR‐663 in 42 patients with LN and 10 healthy controls. Results: As compared with controls, LN patients had lower glomerular expression of miR‐638 (P < 0.001) but higher tubulointerstitial expression of this target (P = 0.001). Both glomerular and tubulointerstitial expression of miR‐198 were higher in LN patients than controls (P < 0.001). For miR‐146a, LN patients only had higher expression in glomerulus (P = 0.005) but not in tubulointerstitium. Tubulointerstitial miR‐638 expression was significantly correlated with proteinuria (r = 0.404; P = 0.022) and disease activity score (r = 0.454; P = 0.008), while glomerular miR‐146a expressions were correlated with estimated GFR (r = 0.453; P = 0.028) and histological activity index (r = 0.494; P = 0.027). Conclusion: We found that intra‐renal expression of miR‐638, miR‐198 and miR‐146a are differentially expressed between LN patients and normal controls. Furthermore, the degree of change in glomerular miR‐146a and tubulointerstitial miR‐638 expression correlated with clinical disease severity. The results suggested that these miRNA targets may play a role in the pathogenesis of lupus nephritis.     

Gene expression of TWEAK/Fn14 and IP-10/CXCR3 in glomerulus and tubulointerstitium of patients with lupus nephritis

Aim: The role of the tumour necrosis factor‐like weak inducer of apoptosis (TWEAK)/Fn14 and interferon‐inducible protein (IP‐10)/CXCR3 axis in the pathogenesis of lupus nephritis were studied. Methods: The mRNA expression of TWEAK, Fn14, IP‐10 and CXCR3 were quantified in the glomerulus and tubulointerstitium of 42 patients with lupus nephritis (LN group) and 10 healthy controls. Results: As compared to controls, LN patients had higher glomerular expression of TWEAK and Fn14, but glomerular CXCR3 expression was lower in the LN group. Similarly, the LN group had higher tubulointerstitial expression of TWEAK and Fn14, but lower tubulointerstitial expression of CXCR3, than controls. Glomerular TWEAK expression of class V nephritis was significantly higher than class IV nephritis. Glomerular expression of CXCR3 significantly correlated with proteinuria (r = ?0.532; P = 0.019), whereas tubulointerstitial CXCR3 significantly correlated with serum creatinine (r = ?0.447; P = 0.029). Conclusion: In patients with lupus nephritis, there is an increase in intra‐renal expression of TWEAK and Fn14, and a decrease in CXCR3 expression. Intra‐renal expression of CXCR3 correlates with proteinuria and renal function. Our findings suggest that the TWEAK/Fn14 and IP‐10/CXCR3 axis may contribute to the pathogenesis of lupus nephritis.     

Levels of IL-17 and Th17/Treg ratio reflect clinical and pathological activity in patients with lupus nephritis

Objective To explore the correlation of Th17/Treg ratio and related cytokines with clinical and pathological activity in patients with lupus nephritis (LN). Methods The patients with lupus nephritis were enrolled into this study from June 2011 to Feb 2012. The demographic data, clinical activity and pathological index were recorded and analyzed in details. The frequency of Th17 and Treg in peripheral blood CD4+ T lymphocytes was tested by flow cytometry and the ratio of Th17 to Treg was calculated. The levels of such cytokines as IL-6, IL-10, IL-17, IL-23, TGF-β1 were detected by ELISA. Results A total of 60 patients with LN were enrolled in this study. Of them, 90% were female, 10% were male, the average age was (36.39±14.23) (14-75) years old, the duration was 1.00(0.33-9.25) years, the average SLEDAI was (9.50±4.61). Compared with control group, the ratio of Th17 to Treg in LN group was significantly higher [(0.95±0.67) vs (0.29±0.13), P＜0.05]; further the Th17/Treg ratio in active LN group was much higher [(1.33±0.71) vs (0.57±0.33), P＜0.01] compared with inactive LN group. The ration of Th17 to Treg was positively correlated with SLEDAI and AI (r＝0.650, P＜0.01; r＝0.675, P＜0.01). The level of serum IL-10 was negatively correlated with SLEDAI and AI(r＝-0.567, P＜0.01; r＝-0.422, P＜0.01). The level of serum IL-17 was positively correlated with SLEDAI and AI (r＝0.559, P＜0.01; r＝0.479, P＜0.01). The level of IL-23 was positively correlated with SLEDAI and AI (r＝0.339, P＜0.05; r＝0.350, P＜0.05). The levels of serum anti-dsDNA and C3 were not correlated with SLEDAI and AI in patients with LN(P＜0.01). As the diagnostic indicator of active LN(SLEDAI≥10), the AUCs of Th17/Treg, IL-17, IL-23 were 0.92 (0.83-1.00), 0.91 (0.81-1.00) and 0.67(0.51-0.83), respectively. As the diagnostic marker of AI＞8,the AUCs of Th17/Treg and IL-17 were 0.87(0.76-0.99) and 0.84 (0.69-0.99). Conclusions The ratio of Th17 to Treg and the level of serum IL-17 are good indicator for evaluating both clinical and pathological activity in patients with LN. The levels of IL-10 and IL-23 show better correlation with SLEDAI and AI than the traditional indicator anti-dsDNA and C3.     

Lower urinary-interleukin-1 receptor-antagonist excretion in IgA nephropathy than in Henoch-Sch?nlein nephritis.

BACKGROUND: IgA nephropathy (IgAN) and Henoch-Sch?nlein nephritis (HSN) share many clinical, histological and immunological features. It has been postulated that these two conditions have a common pathogenesis and that HSN might be a systemic form of IgAN. Activity of interleukin-1beta (IL-1beta) in urine has been found to be higher in IgAN and HSN patients than in healthy controls. Interaction between IL-1beta and interleukin-1 receptor antagonist (IL-1ra) plays a significant role in the regulation of inflammatory responses. We studied levels of urinary excretion of IL-1beta and IL-1ra in patients with IgAN and HSN. METHODS: Amounts of IL-1beta and IL-1ra excreted in 24-h urine samples collected from 241 IgAN, 26 HSN patients and from 33 healthy controls were determined. Results were expressed as cytokine/creatinine (ng/mmol) ratios. RESULTS: Urinary IL-1beta excretion by the IgAN and HSN patients was no greater than urinary IL-1beta excretion by healthy controls. Urinary IL-1ra excretion by the IgAN patients was lower than urinary IL-1ra excretion by healthy controls (P < 0.05) and by the HSN patients (P < 0.01). In both patients and controls women had significantly higher IL-1ra, IL-1beta excretion levels and IL-1ra/IL-1beta ratios. The differences in urinary excretions of IL-1ra by the healthy controls and by the IgAN and HSN patients were significant in both sexes. Excretion of IL-1beta or IL-1ra did not correlate with excretion of urinary protein, duration of the disease or any histopathological variable. However, histopathological changes in renal biopsy specimens from patients with IL-1ra/IL-1beta ratios above normal were significantly milder than in renal biopsy specimens from patients with low or normal IL-1ra/IL-1beta ratios. CONCLUSION: Urinary IL-1ra levels in IgAN patients were lower than urinary IL-1ra levels in healthy controls or HSN patients, a finding which may indicate that the two diseases have a different pathogenesis. Whether the male predominance in IgAN and HSN and the worse outcomes in males that have been reported previously in IgAN and HSN are connected with the lower excretion of IL-1ra and consequently lower IL-1ra/IL-1beta ratios in male patients than in female patients needs more thorough investigation.     

Detection of urinary macrophages expressing the CD16 (Fc gamma RIII) molecule: a novel marker of acute inflammatory glomerular injury

BACKGROUND: The CD16 antigen is the Fc gamma receptor III. CD14+CD16+ cells are proinflammatory monocytes/macrophages (Mo/M phi) that constitute a minor population in the peripheral blood of healthy individuals. Little is known about the expression of CD16 antigen on Mo/M phi in glomerulonephritis. METHODS: Flow cytometric analyses were performed on urine and blood samples obtained from 209 patients with various renal diseases. Patients variously suffered from rapidly progressive crescentic glomerulonephritis (RPGN), membranoproliferative glomerulonephritis (MPGN), postinfectious acute glomerulonephritis (AGN), Henoch-Sch?nlein purpura nephritis (HSPN), IgA nephropathy (IgAN), membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS), lupus nephritis (LN), acute interstitial nephritis, hereditary nephropathy, idiopathic renal hematuria (IRH), and renal stone. RESULTS: The CD16+ M phi population of cells was present in the urine of hematuria-positive patients with proliferative glomerulonephritis, including AGN, IgAN, RPGN, MPGN, and LN with acute inflammatory lesions, such as endocapillary proliferation, tuft necrosis, and cellular crescents. In contrast, the urinary CD16+ M phi population was negligible in hematuria-positive patients with nonproliferative renal disease, including hereditary nephropathy, IRH, and renal stone and also in patients with proliferative glomerulonephritis lacking acute inflammatory lesions. Total urinary M phi of these patients were much less than those of patients having proliferative glomerulonephritis with acute inflammatory lesions. Transient expansion of the CD16+ M phi population in urine was observed during the acute exacerbation of urinary abnormalities, whereas the disappearance of CD16+ M phi closely preceded the amelioration of urinary abnormalities in patients with proliferative glomerulonephritis. In 38 of the 98 patients positive for CD16+ M phi population in urine, the CD16+ Mo population was negligible in peripheral blood. Immunohistochemically, CD16+ M phi were present in the glomeruli of active proliferative glomerulonephritis, whereas such cells were absent in inactive proliferative glomerulonephritis or nonproliferative glomerular diseases. CONCLUSION: CD16+ M phi may be effector cells involved in the acute inflammation common to all types of proliferative glomerulonephritis. Furthermore, the detection of CD16+ M phi in urine, as well as urinary M phi counts, may serve as a useful indicator of the active stage of proliferative glomerulonephritis.     

活动性狼疮肾炎患者外周血单个核细胞钙调神经磷酸酶活性的检测及白细胞介素-4表达变化

目的：检测活动性狼疮肾炎（LN）患者外周血单个核细胞（PBMC）白细胞介素-4（IL-4）表达及其与钙调神经磷酸酶（Calcineurin，CaN）活性的关系。方法：体外培养活动性LN患者PBMC，应用发色底物法检测胞浆CaN活性，逆转录PCR检测IL-4mRNA表达。结果：（1）在单纯培养情况下，正常对照组和LN组PBMC均出现一定量CaN活化，活动性LN组显著高于正常对照组[（46．08±5．58）mmol／mg．pr vs（8．81±3．61）mmol／mg．pr，P〈0．01]；在PMA＋Ionomyci刺激下，各组CaN活性均升高，活动性LN组CaN活性明显高于正常对照组[（69．34±12．59）mmol／mg．pr vs（37．12±11．57）mmol／mg．pr，P〈0．01]；（2）LN患者PBMC在单纯培养和PMA＋Ionomycin刺激时IL-4蛋白和mRNA表达均显著高于相应的对照组（P〈0．05）；（3）在单纯培养和PMA＋Ionomycin刺激时，FK506对LNPBMC表达IL-4蛋白和mRNA均有显著抑制作用（P〈0．01）。结论：LN患者PBMC存在CaN过度活化；LN患者PBMC高效表达IL-4与其CaN过度活化密切相关，通过阻断CaN活性可调控IL-4表达。     

Daily urinary interleukin-11 excretion correlated with proteinuria in IgA nephropathy and lupus nephritis

Interleukin-11 (IL-11) is a multifunctional cytokine with both thrombopoietic and anti-inflammatory effects. In an animal study IL-11 was shown to reduce proteinuria in mice with necrotizing glomerulonephritis. The purpose of this current study is to explore the role of IL-11 in human glomerulonephritis. Subjects of this study were patients with proteinuria (daily urine protein excretion >40 mg/m² per hour) and underlying pathology of IgA nephropathy (IgAN) (n=20), lupus nephritis (LN) (n=40), and idiopathic nephrotic syndrome (INS) (n=68). Daily urinary IL-11 level was measured by enzyme-linked immunosorbent assay (ELISA). Correlation between urinary IL-11 and urinary protein was determined by Pearson’s correlation coefficient. Another five patients with serial data of urinary protein, IL-11 and IL-11 messenger RNA (mRNA) expression in urine sediment are presented. The correlation between urinary IL-11 and daily urinary protein was significant for patients with IgAN (r=0.596, P=0.006) and LN (r=0.630, P<0.001), but not for patients with INS (r=0.030, P=0.812). Serial data revealed the same correlation. Furthermore, the peak of urinary IL-11 mRNA preceded that of urinary IL-11. We conclude that daily urinary IL-11 excretion is correlated with urinary protein loss in nephritis having local T helper (Th)1 predominant immune response, such as IgAN and LN. Local IL-11 production may serve as a counter cytokine against Th1-mediated inflammation.     

激素联合来氟米特治疗狼疮性肾炎疗效的观察

目的 了解来氟米特治疗Ⅳ型狼疮性肾炎的临床效果、安全性和不良反应.方法 59例狼疮性肾炎患者的肾活组织检查(简称活检)显示为狼疮性肾炎,应用来氟米特联合糖皮质激素治疗6个月.用药期间监测血、尿常规、24 h尿蛋白定量、肝、肾功能、抗核抗体及抗双链抗体滴度、红细胞沉降率和补体C3等,6个月后行疗效和安全性的评价.结果 来氟米特治疗狼疮性肾炎尿蛋白缓解率为72.4%,高于环磷酰胺冲击治疗缓解率(57%),狼疮性肾炎活动性指标缓解率也高于后者.结论 来氟米特联合糖皮质激素治疗能有效地控制狼疮活动且不良反应轻,耐受性好.     

Cytokines and adhesion molecules in renal vasculitis and lupus nephritis

Background: Plasma levels of some pro-inflammatory cytokines and soluble adhesion molecules have been suggested to be useful parameters to assess the activity of antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis and lupus nephritis. We hypothesized that the renal activity of these diseases is better reflected by the urinary excretion and fractional excretion of these molecules. Methods: Plasma levels and urinary excretion of tumour necrosis factor-&agr; (TNF-&agr;), interleukin (IL)-6, IL-8, and the soluble cell adhesion molecules sICAM-1 and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 15 patients with ANCA-positive renal vasculitis (eight active, ANCA-A; six in remission, ANCA-R), six patients with active lupus nephritis (LN), 15 patients with IgA nephropathy (IgAN) and nine healthy subjects. Fractional excretion of selected cytokines and adhesion molecules was also calculated. Results: Patients with ANCA-A had increased urinary excretion and fractional excretion of TNF-&agr; (9.27±3.19% vs 0.58±0.02%, P<0.01), IL-6 (120.79±65.83% vs 1.89±0.34%, P<0.01) and increased fractional excretion of IL-8 (23.34±6.38% vs 2.56±1.07%, P<0.01) and sVCAM-1 (0.81±0.33% vs 0.03±0.02%, P<0.01) compared with controls. Urinary excretion of TNF-&agr; and IL-6 and fractional excretion of TNF-&agr;, IL-6 and IL-8 were higher in ANCA-A than in ANCA-R. Patients with LN had increased plasma TNF-&agr; (20.52±2.01 pg/ml vs 12.33±0.23 pg/ml, P<0.05) and sVCAM-1 (1537.88±276.36 ng/ml vs 692.26±44.42 ng/ml, P<0.05) and increased urinary excretion of TNF-&agr; (2.81±0.51 &mgr;g/mol creat vs 0.98±0.05 &mgr;g/mol creat, P<0.01), IL-8 (35.78±14.03 &mgr;g/mol creat vs 12.46±5.19 &mgr;g/mol creat, P<0.05) and sVCAM-1 (48.98±20.20 &mgr;g/mol creat vs 2.92±1.35 &mgr;g/mol creat, P<0.01) compared with controls. Patients with IgAN had, in comparison with controls only increased plasma TNF-&agr; (18.10±0.57 pg/ml vs 12.33±0.23 pg/ml, P<0.05). Conclusions: Urinary excretion and fractional excretion, but not plasma levels of selected proinflammatory cytokines (TNF-&agr;, IL-6 and IL-8) were increased in patients with active ANCA-positive renal vasculitis, but not in ANCA positive vasculitis in remission. These parameters may be useful to monitor the activity of this disease.     

The risk of pregnancy in patients with lupus nephritis

Since many women with systemic lupus erythematosus (SLE) are of child-bearing age and have normal fertility, the clinician must often face many problems relating to pregnancy in patients with lupus nephritis. These include the influence of lupus nephritis on fetal outcome, obstetric complications, and the influence of pregnancy on SLE. Studies published in the 1960s underlined the increased fetal and maternal risk and recommended against pregnancy in lupus patients. The prognosis for non-pregnant SLE active patients was also poor, making it difficult to know whether pregnancy altered the prognosis of the disease. Recent prospective studies indicate that the majority of lupus mothers can sustain pregnancy without detrimental effects, providing that the pregnancy is planned during the inactive phase of the disease. Nevertheless the fetal risk, although progressively reduced during the last 40 years, continues to be higher than in pregnancies of healthy women particularly in patients with antiphospholipid antibodies.     

淋巴细胞功能相关抗原1共刺激作用在活动性狼疮肾炎中的作用

目的探讨淋巴细胞功能相关抗原(LFA)1及其信号分子在狼疮肾炎发病机制中的作用。方法 利用免疫沉淀、免疫印迹和RTllPCR技术检测了LFA-1共刺激对19例活动性狼疮肾炎(LN)患者外周血单个核细胞(PBMC)P13-K磷酸化产物、IL-10 mRNA表达的影响。以14例健康献血员作为对照。结果 在CD3 mAb30 ng/ml存在的情况下,LFA-1mAb共刺激明显提高了活动性LN患者PBMC P13-K磷酸化产物表达(P<0.01),伴有IL-10 mRNA表达和蛋白含量增加(P<0.01),抗lFA-1抗体(5μmol/L)加入后明显抑制了P13-K磷酸化产物表达(P<0.01)。在CD3 mAb和LFA-1mAb协同刺激的情况下,P13-K特异抑制剂Wortamannin的加入明显抑制了LN患者PBMCIL-10 mRNA水平和蛋白含量(P<0.01)。结论 LFA-1作为共刺激分子过度活化P13-K可能介导了活动性狼疮肾炎IL-L 10的高效表达。     

Clinical significance of renal biopsies showing mixed mesangial and global proliferative lupus nephritis

Renal biopsies of 70 children with systemic lupus erythematosus were categorized, according to the World Health Organization classification, as normal (five, 7%), mesangial (23, 33%), focal segmental proliferative (11, 16%), diffuse global proliferative (20, 29%) (ie, greater than or equal to 80% of glomeruli showing mesangioendothelial cell proliferation and/or deposition of immune complexes along the subendothelial margin of glomerular capillaries), and membranous (six, 8%) lupus nephritis (LN). In addition, five (7%) biopsies showed global proliferative LN in less than 80% of glomeruli and mesangial LN in the others. We assessed the renal status of these five patients at the time of renal biopsy and at outcome following prednisone treatment, with or without azathioprine. Four patients improved and later had either a normal urinalysis or only trace proteinuria. A low chronicity index was calculated on the biopsies of these patients. The fifth patient, whose condition did not improve, demonstrated a high chronicity index on renal biopsy. Overall, the renal status at outcome in the patients showing mixed mesangial and global proliferative LN more closely resembled that of patients with mesangial than diffuse global proliferative LN.     

正常人与原发性肾小球肾炎及狼疮性肾炎患者血尿IL-18水平比较

目的:探讨IL-18在原发性肾小球肾炎(PGN)及狼疮性肾炎(LN)发生、发展中的作用,以及寻找有助于两类疾病的鉴别诊断和对肾组织炎症活动程度进行评估的指标。方法:应用酶联免疫吸附检测(enzyme-linkedimmunosorbent assay,ELISA)法测定16例正常人、21例原发性肾小球肾炎(PGN)患者和18例LN患者血浆和尿液IL-18水平的变化。结果:LN患者血浆及尿液IL-18水平显著高于正常对照组(P均<0.001)和PGN组(P均<0.05),而且WHOⅣ型LN患者血浆及尿IL-18水平均明显高于非Ⅳ型LN患者(P<0.05);PGN患者尿液IL-18水平也高于正常人(P<0.05),但血浆IL-18水平与正常人比较无统计学差异(P>0.05);LN患者血浆IL-18水平与SLEDAI呈正相关(P<0.01),而尿IL-18水平与狼疮性肾炎RHSAI是密切正相关(P<0.001),但尿IL-18水平与血浆IL-18水平相关性没有统计学意义(P>0.05)。结论:IL-18参与LN的全身免疫病理过程,但可能仅参与PGN肾组织局部炎症过程;血浆IL-18检测可能有助于区分LN和PGN,尿IL-18的检测可望作为一项估计LN肾组织病变活动程度的有用指标。