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1.
The Clinical and Renal Biopsy Predictors of Long-term Outcome in Lupus Nephritis: A Study of 87 Patients and Review of the Literature 总被引:3,自引:0,他引:3
ESDAILE JOHN M.; LEVINTON CAREY; FEDERGREEN WARREN; HAYSLETT JOHN P.; KASHGARIAN MICHAEL 《QJM : monthly journal of the Association of Physicians》1989,72(3):779-833
The prognostic markers in 87 consecutive patients with lupusnephritis who underwent renal biopsy are reported for five clinicallyrelevant long-term outcomes - renal Insufficiency, renal failure,death due to renal systemic lupus erythematosus, death due tonon-renal SLE and death due to SLE, both renal and non-renalWe have demonstrated that a number of previously neglected orrarely studied predictors were Important prognostic markers.These Included the duration of renal disease before biopsy,overall severity of SEE, as well as the presence of vasculitis,hypertension or a comorbid ailment Furthermore, the study confirmsthe predictive Importance of serum creatinine, 24-h urinaryexcretion of protein., C3, and of the activity and chronicityindices on biopsy. However, overall a simple measure of tubulointerstitialdisease was the best predictor obtained from biopsy. Prognostic models based on clinical data alone were developedfor each of the five outcomes. The models amplify our clinicalunderstanding of lupus nephritis. Markers of renal severitywere most Important In predicting renal outcomes such as renalInsufficiency and renal failure. Prognostic factors less directlyrelated to renal disease (comorbidity and vasculitis) were importantpredictors of fatality. A marker of immunologic disease activity(C3) was a valuable predictor for many of the outcomes. Thusmarkers of disease severity reflecting organ damage due to SLEand other comorbid conditions could be combined with markersof Immunologic activity to predict a variety of outcomes ofrelevance to a clinician. When biopsy data obtained by light or electron microscopy wereevaluated for their ability to add new predictive informationto the clinical models, only a limited value for biopsy wasnoted. It is likely that this reflected the close correlationalrelationships between clinical and biopsy variables, the strongclinical models generated, and the inclusion in the clinicalmodels of the previously neglected clinical variables, durationof renal disease before biopsy and the presence of vasculitisor comorbid disease. 相似文献
2.
Fabrizio Conti Fulvia Ceccarelli Antonietta Gigante Biagio Barbano Carlo Perricone Laura Massaro Francesco Martinelli Francesca Romana Spinelli Kostantinos Giannakakis Guido Valesini Rosario Cianci 《Ultrasound in medicine & biology》2014,40(11):2573-2580
We analyzed the association between the renal arterial resistive index (RI) and the histologic features of lupus nephritis. All consecutive patients with systemic lupus erythematosus (SLE) who required a kidney biopsy were enrolled. The study protocol included ultrasonographic assessment to measure the RI and kidney biopsy (International Society of Nephrology/Renal Pathology Society classification). A RI > 0.7 was considered pathologic. Patients with non-renal SLE and healthy patients were studied as control groups. We enrolled 42 patients with renal SLE, 10 with non-renal SLE and 14 healthy patients: their mean (±standard deviation) RI values were 0.64 ± 0.08, 0.60 ± 0.04 and 0.59 ± 0.01, respectively (p = not significant). RIs > 0.7 were recorded only in patients with renal SLE (5/42, 11.9%). The percentage of patients with a pathologic RI was significantly higher in class IV nephritis in comparison with other classes (p < 0.009). In conclusion, we found a significant correlation between pathologic RI and class IV nephritis, suggesting a role for RI as a severity marker. 相似文献
3.
《Expert opinion on biological therapy》2013,13(12):1559-1561
Abatacept is a selective T-cell co-stimulation modulator that inhibits full T-cell activation and subsequent antibody production by B cells. Despite the efficacy of abatacept in murine lupus, randomized controlled trials in human SLE do not reveal benefit of abatacept in non-renal and renal lupus. While problems in the study design and the primary efficacy end points may contribute to the negative results of these trials, post hoc analyses using alternative definitions for clinical response suggest the possibility that abatacept may have beneficial effects in active lupus arthritis and proliferative nephritis. Future clinical trials of abatacept should target on defined subsets of SLE patients, utilize multiple pre-defined outcomes based on experience from previous studies and determine the best timing of adding abatacept on a background of minimal immunosuppressive therapies. 相似文献
4.
OBJECTIVE: To determine the clinical value of assaying serum levels of neopterin, tumor necrosis factor-alpha (TNF-alpha) and soluble tumor necrosis factor receptor II (p75) (sTNFRII) in patients with systemic lupus erythematosus (SLE), manifested clinically with lupus nephritis (LN), neuropsychiatric lupus erythematosus (NPLE), and/or vasculitis compared with established parameters (complements C3 and C4). PATIENTS AND METHODS: Serum concentrations of neopterin, TNF-alpha and sTNFRII were studied in 40 female patients with SLE at various degrees of disease activity and in 10 healthy controls, matched for age and sex, using an ELISA kit. Disease activity was assessed by the SLE disease activity index (SLEDAI) score. Thirty-five, 30 and 28 of our patients presented with LN, NPLE and/or vasculitis, respectively, as the main clinical manifestation. RESULTS: Serum levels of neopterin, TNF-alpha and sTNFRII were significantly increased, while the TNF-alpha/sTNFRII ratio, C3 and C4 levels of SLE patients were significantly lower than those of healthy controls. Neopterin and sTNFRII were the only parameters that showed significantly higher levels in SLE patients with mild activity compared to normal subjects and were the only parameters that showed a significant elevation in membranous nephritis and in mild NPLE compared to patients without nephritis and NPLE. Patients with vasculitis had significant elevation of serum neopterin, TNF-alpha and sTNFRII levels compared to patients without vasculitis. We found significant correlations between all measured variables and the SLEDAI score. Also, serum neopterin levels showed significant positive correlation with serum TNF-alpha, sTNFRII and TNF-alpha/sTNFRII levels. Serum neopterin and sTNFRII could be used to identify SLE patients from normals with a sensitivity and specificity of 100%. Multivariate linear regression analysis showed that serum sTNFRII was the only significant independent variable among parameters for prediction of SLE disease activity. CONCLUSION: We suggest that serum sTNFRII and neopterin are more sensitive markers of disease activity than TNF-alpha, C3 or C4. However, sTNFRII may be a clinically useful independent marker for prediction of SLE disease activity and to differentiate normal subjects from those having mild SLE. 相似文献
5.
This study describes the clinical and pathological characteristics of 74 patients with lupus nephritis classified according to renal biopsy findings using light, electron and immunofluorescent microscopy, and further, assesses the significance of subendothelial deposits in evaluating disease activity. In membranous lupus nephritis (14 cases), many cases showed normal renal function even with the nephrotic syndrome, although five cases had little or no urinary abnormalities. Glomerular cellular proliferation was very mild and subepithelial deposits with a few mesangial deposits were the main pathological alterations. Mesangial proliferative lupus nephritis (17 cases) clinically had very mild renal disease. Renal biopsies in this group revealed mesangial deposits with slight cellular proliferation. Although clinical features of mild diffuse proliferative lupus nephritis (16 cases) were similar to those of mesangial lupus nephritis, glomerular loop deposits were seen in addition to mesangial deposits. In moderate diffuse proliferative lupus nephritis (17 cases), renal function was slightly decreased, moderate proteinuria with haematuria were found, and C3 level was low. Renal biopsies showed active proliferative changes, and subendothelial deposits were frequently seen. In severe diffuse proliferative lupus nephritis (10 cases), the duration from onset of SLE to renal biopsy was short. Impairment of renal function, and nephrotic syndrome with haematuria and hypocomplementemia were frequent. Only three patients survived in this group. Renal biopsies demonstrated highly active proliferative and necrotizing changes, and electron microscopy showed massive subendothelial and mesangial deposits accompanied by subepithelial and intramembranous deposits. The amount of subendothelial deposits correlated with those of mesangial deposits and subepithelial deposits in the cases with diffuse proliferative lupus nephritis. Urinary protein loss and histologic activity showed statistically significant correlations with the amount of subendothelial deposits, but C3 levels and creatinine clearance revealed negative correlations with those deposits. 相似文献
6.
Kozlovskaia NL Shilov EM Meteleva NA Varshavskiĭ VA Miroshnichenko NG Samokishina NA Serova AG Nesterova SG 《Terapevticheski? arkhiv》2006,78(5):21-31
AIM: To ascertain clinical and morphological features of lupus nephritis (LN) in systemic lupus erythematosus (SLE) associated with antiphospholipid syndrome (APS). MATERIAL AND METHODS: Immunological markers of SLE and APS, clinical picture, urine indices were examined in 138 patients with SLE, APS and renal dysfunction. RESULTS: LN associated with APS is characterized with marked arterial hypertension, such patients had arterial thromboses more frequently than patients with isolated LN. Patients with anticardiolipin antibodies have arteriolosclerosis, in APS - diffuse interstitial sclerosis. CONCLUSION: Renal impairment in SLE may run not only with LN but also with thrombotic microangiopathy modifying clinical symptoms and course of the disease. 相似文献
7.
目的探讨系统性红斑狼疮合并肾炎患者肾穿刺活检术的护理方法。方法回顾性分析并总结2010年9月至2011年5月,哈尔滨医科大学附属第一医院风湿免疫科收治的43例系统红斑狼疮合并肾炎患者的临床资料。结果有效的术前、术后护理可以明显缓解患者的焦虑情绪,使患者心理状态平稳,使其能够正确地配合医生的手术操作,减少术后并发症,减轻患者的不适感;43例患者手术后都恢复到术前的状态,能够进一步接受系统性红斑狼疮的专科治疗。结论加强系统性红斑狼疮合并肾炎患者肾穿刺活检术的护理,可以明显减少并发症的出现,为今后临床工作中提高肾穿刺活检术的成功率及患者的生活质量提供依据。 相似文献
8.
Peutz-Kootstra CJ de Heer E Hoedemaeker PJ Abrass CK Bruijn JA 《The Journal of laboratory and clinical medicine》2001,137(4):244-260
Lupus nephritis is a frequent and severe complication of SLE. In the last decades, animal models for SLE have been studied widely to investigate the immunopathology of this autoimmune disease because abnormalities can be studied and manipulated before clinical signs of the disease become apparent. In this review an overview is given of our current knowledge on the development of lupus nephritis, as derived from animal models, and a hypothetical pathway for the development of lupus nephritis is postulated. The relevance of the studies in experimental models in relationship with our knowledge of human SLE is discussed. 相似文献
9.
Kidney biopsy in SLE. I. A clinical-morphologic evaluation 总被引:2,自引:0,他引:2
D D Gladman M B Urowitz E Cole S Ritchie C H Chang J Churg 《The Quarterly journal of medicine》1989,73(272):1125-1133
The relationship between renal morphology and clinical disease was analysed in 148 patients with SLE attending a lupus clinic. Patients were not selected for renal disease. Renal tissue was assessed according to the World Health Organization classification of lupus nephritis, the presence of active and chronic lesions was recorded and disease activity was measured according to a standard protocol. All sections of the classification were represented in this group of patients. Active and chronic lesions were more likely to occur among patients with Class III/IV (proliferative glomerulonephritis), than in any other category. Patients with Class III/IV biopsy were more likely to have evidence of clinical renal disease than patients in Class II (mesangial). However, almost half of the Class II patients had some evidence of renal disease, including elevated serum creatinine, as well as important non-glomerular lesions. Without biopsy they might have been thought to have proliferative lesions and been treated more aggressively. Two patients with proliferative glomerulonephritis had no clinical evidence of renal disease. Thus, at the time of biopsy results renal histological examination did not uniformly correlate with clinical renal disease. 相似文献
10.
J M Esdaile W Federgreen H Quintal S Suissa J P Hayslett M Kashgarian 《The Quarterly journal of medicine》1991,81(295):907-918
The short-term prognosis of lupus nephritis was evaluated by assessing serum creatinine 12 months after renal biopsy in 87 patients with lupus nephritis. On univariate analysis, significant clinical and laboratory predictors of this outcome included clinical signs of renal injury (serum creatinine, 24-hour urinary protein, prolonged renal disease, nephrotic syndrome, serum albumin), as well as thrombocytopenia, older age, and coexisting illness or hypertension at the time of biopsy. On renal biopsy, diffuse proliferative nephritis, higher activity, chronicity, or tubulointerstitial scores, or subendothelial or subepithelial electron dense deposits predicted a higher serum creatinine 12 months after biopsy. A clinical predictive model was developed which included as independent predictors serum creatinine, age, platelet count and 24-hour urinary protein. Any one of three biopsy variables added information to the clinical prediction model: a marked quantity of subendothelial deposits (p = 0.02), a higher activity index score (p = 0.02), or the presence of diffuse proliferative lupus nephritis (p = 0.05). However, the relative predictive accuracy of the clinical model did not improve with the addition of any of the biopsy variables. The value of renal biopsy in lupus nephritis is discussed based on the ability of biopsy information to confirm the prognosis, to add new predictive information for a group of subjects, and to improve predictive accuracy for individual patients. 相似文献
11.
Kashgarian M 《Transfusion science》1992,13(2):135-144
The renal biopsy plays an important role in the clinical evaluation of patients with lupus erythematosus. From numerous studies of renal biopsies in patients with lupus nephritis, it has become clear that although renal lesions are quite varied, the pattern of renal involvement correlates well with the clinical outcome. The broad spectrum of the lesions seen in lupus nephritis has been attributed to individual differences in the immune response in different patients or in the same patient during the course of illness. A classification of lupus nephritis authorized by the World Health Organization is presented. The classification combines all of the morphologic modalities of biopsy interpretation and semiquantitative assessment of activity and chronicity. The clinical correlation of this histologic classification is emphasized and demonstrates that the specific nature of the renal histopathology can predict both the acute and long term course of renal disease in lupus nephropathy and be useful in determining the management of individual patients. 相似文献
12.
Samantha A. Chalmers Rajalakshmy Ayilam Ramachandran Sayra J. Garcia Evan Der Leal Herlitz Jeanette Ampudia Dalena Chu Nicole Jordan Ting Zhang Ioannis Parodis Iva Gunnarsson Huihua Ding Nan Shen Michelle Petri Chi Chiu Mok Ramesh Saxena Krishna R. Polu Stephen Connelly Cherie T. Ng Chandra Mohan Chaim Putterman 《The Journal of clinical investigation》2022,132(1)
T cells are central to the pathogenesis of lupus nephritis (LN), a common complication of systemic lupus erythematosus (SLE). CD6 and its ligand, activated leukocyte cell adhesion molecule (ALCAM), are involved in T cell activation and trafficking. Previously, we showed that soluble ALCAM is increased in urine (uALCAM) of patients with LN, suggesting that this pathway contributes to disease. To investigate, uALCAM was examined in 1038 patients with SLE and LN from 5 ethnically diverse cohorts; CD6 and ALCAM expression was assessed in LN kidney cells; and disease contribution was tested via antibody blockade of CD6 in murine models of SLE and acute glomerulonephritis. Extended cohort analysis offered resounding validation of uALCAM as a biomarker that distinguishes active renal involvement in SLE, irrespective of ethnicity. ALCAM was expressed by renal structural cells whereas CD6 expression was exclusive to T cells, with elevated numbers of CD6+ and ALCAM+ cells in patients with LN. CD6 blockade in models of spontaneous lupus and immune-complex glomerulonephritis revealed significant decreases in immune cells, inflammatory markers, and disease measures. Our data demonstrate the contribution of the CD6/ALCAM pathway to LN and SLE, supporting its use as a disease biomarker and therapeutic target. 相似文献
13.
Kallikrein genes are associated with lupus and glomerular basement
membrane–specific antibody–induced nephritis in mice and
humans
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《The Journal of clinical investigation》2009,119(4):911-923
Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody–induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that may be responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody–induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family, which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody–induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms, some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody–induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody–induced nephritis and lupus. 相似文献
14.
Virtually all preparations of DNA used to detect antibody to native DNA (nDNA) by binding assays have been found to be subtly contaminated by single stranded DNA. Because recent DNA binding data have directly challenged the unique role previously attributed to these antibodies in systemic lupus erythematosus (SLE), resolution of the consequent ambiguity is of theoretical and practical importance. It is proposed that a synthetic nDNA molecule (dAT) might circumvent this difficulty by being antigenically equivalent to nDNA while, on theoretical grounds, lacking significant contamination with single stranded DNA or other cellular antigens. These expectations were generally confirmed by biochemical and immunological analyses. In clinical studies, sera from 124 pateints with SLE and from controls were examined for their ability to bind dAT. In contrast to results with KB binding, patients with non-SLE rheumatologic disorders were indistinguishable from normals by dAT binding. dAT binding was elevated in 85% of sera from SLE patients with clinically-judged active nephritis but in only 9% of those with inactive renal disease. Active non-renal disease, including cerebritis, was not associated with increased dAT binding. Individual non-lupus sera which bound increased amounts of KB DNA, failed to bind dAT. It is suggested that such binding resulted from contaminating non-nDNA antigens. When elevated, dAT binding, like KB binding, varied with disease activity and might thus be useful as a parameter thereof. In several patients elevated dAT binding led to the finding, on biopsy, of clinically silent, active, diffuse proliferative nephritis. It is concluded that use of synthetic nDNA antigens such as dAT may offer theoretical and practical advantages over naturally-derived preparations in detecting anti-nDNA, both clinically and for investigational purposes. Also, caution is urged in interpreting DNA binding data derived from incompletely characterized systems, particularly with regard to the occurrence of anti-nDNA antibodies in serum. 相似文献
15.
目的:分析狼疮性肾炎(LN)患者的死亡原因及危险因素,探讨减少死亡率的策略。方法:以2003年1月-2012年12月我院住院期间死亡的LN患者56例为研究组,并与同期住院存活的LN患者129例为对照组,比较两组的临床特点、死亡原因和死亡危险因素。结果:LN患者第一位死亡原因为SLE本身(53.5%),其次为感染(21.4%)及心血管疾病(17.9%);与对照组比较,研究组患者的急性肾损伤、慢性肾衰竭进入透析、狼疮脑病、浆膜炎及感染等的发生率明显高于对照组(P0.05或0.01);狼疮脑病、慢性肾衰竭、SLEDAI升高是LN患者死亡的独立危险因素(OR1,P0.05),体重指数(BMI)是LN的保护因素(OR1,P0.05)。结论:SLE本身所致多器官功能衰竭是LN的主要死亡原因,采取合理治疗措施,控制狼疮活动,积极治疗狼疮脑病、慢性肾衰竭,防止感染、纠正营养不良,可能有助于降低LN患者的病死率。 相似文献
16.
MRL-lpr/lpr mice spontaneously develop an autoimmune disease similar to human systemic lupus erythematosus (SLE). Disease manifestations include anti-DNA autoantibody production, arthritis, vasculitis, and an immune-complex glomerulonephritis. The development of autoimmune disease is associated with massive, generalized lymphadenopathy caused by accumulation of an abnormal T-cell population in peripheral lymphoid organs. In MRL-lpr/lpr mice, treatment with E-series prostaglandins ameliorates renal disease and reduces peripheral lymphadenopathy. Little is known about mechanisms of action of E-series prostaglandins in murine lupus or the effects of these agents on other clinically important manifestations of SLE, such as arthritis and vasculitis. To further investigate the effects of an E-series prostaglandin in murine SLE, we administered the prostaglandin, E(1) (PGE(1)) analog misoprostol (1 mg kg(minus sign1) day(minus sign1)) to MRL-lpr/lpr mice for 8 weeks by twice daily subcutaneous injection. At 20 weeks of age, treatment with misoprostol reduced the severity of renal disease and arthritis but did not affect the extent or severity of vasculitis. The beneficial effects of misoprostol on arthritis and renal disease were associated with a significant decrease in splenic and lymph node weight in mice given the PGE(1) analog. This decrease in lymphoproliferation resulted primarily from a generalized reduction in the number of T cells in peripheral lymphoid organs. Thus, T-cell depletion was associated with beneficial effects on arthritis and nephritis in MRL-lpr/lpr mice, supporting a role for T lymphocytes in these disease processes. The ability of E-series prostaglandins to favorably modify autoimmune disease in this murine model suggests that misoprostol may be a useful adjunct to current therapies for the treatment of patients with SLE. 相似文献
17.
ESDAILE JM; FEDERGREEN W; QUINTAL H; SUISSA S; HAYSLETT JP; KASHGARIAN M 《QJM : monthly journal of the Association of Physicians》1991,81(2):907-918
The short-term prognosis of lupus nephritis was evaluated byassessing serum creatinine 12 months after renal biopsy in 87patients with lupus nephritis. On univariate analysis, significantclinical and laboratory predictors of this outcome includedclinical signs of renal injury (serum creatinine, 24-hour urinaryprotein, prolonged renal disease, nephrotic syndrome, serumalbumin), as well as thrombocytopenia, older age, and coexistingillness or hypertension at the time of biopsy. On renal biopsy,diffuse proliferative nephritis, higher activity, chronicity,or tubulointerstitial scores, or subendothelial or subepithelialelectron dense deposits predicted a higher serum creatinine12 months after biopsy. A clinical predictive model was developed which included asindependent predictors serum creatinine, age, platelet countand 24-hour urinary protein. Any one of three biopsy variablesadded information to the clinical prediction model: a markedquantity of subendothelial deposits (p=0.02), a higher activityindex score (p=0.02), or the presence of diffuse proliferativelupus nephritis (p=0.05). However, the relative predictive accuracyof the clinical model did not improve with the addition of anyof the biopsy variables. The value of renal biopsy in lupus nephritis is discussed basedon the ability of biopsy information to confirm the prognosis,to add new predictive information for a group of subjects, andto improve predictive accuracy for individual patients. 相似文献
18.
Monocyte procoagulant activity in glomerulonephritis associated with systemic lupus erythematosus. 总被引:1,自引:3,他引:1
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E H Cole J Schulman M Urowitz E Keystone C Williams G A Levy 《The Journal of clinical investigation》1985,75(3):861-868
Monocyte infiltration and activation of the coagulation system have been implicated in the pathophysiology of glomerulonephritis. In this study, spontaneous procoagulant activity (PCA) was measured in circulating mononuclear cells to determine whether elevated PCA correlated with the presence of proliferative glomerulonephritis in patients with systemic lupus erythematosus (SLE). No increase in PCA was found in 20 patients with end-stage renal failure, 8 patients with glomerulonephritis without SLE, and 10 patients undergoing abdominal surgical or orthopedic procedures as compared with 20 normal controls. In eight patients with SLE but with no apparent active renal disease, PCA was not elevated above normal basal levels. Seven additional patients with SLE who had only mesangial proliferation on biopsy also had no increase in PCA. In contrast, eight patients with focal or diffuse proliferative lupus nephritis, and one patient with membranous nephritis who ultimately developed a proliferative lesion, had a marked increase in PCA with greater than 100 times the base-line levels. The activity was shown to originate in the monocyte fraction of the mononuclear cells and was shown to be capable of cleaving prothrombin directly. The prothrombinase activity was not Factor Xa, because it was not neutralized by anti-Factor X serum and was not inhibited by an established panel of Factor Xa inhibitors. Monocyte plasminogen activator determinations did not correlate with renal disease activity. We conclude that monocyte procoagulant activity, a direct prothrombinase, seems to correlate with endocapillary proliferation in lupus nephritis and could be a mediator of tissue injury. 相似文献
19.
Heterogeneity and clinical significance of glomerular-binding antibodies in systemic lupus erythematosus. 总被引:3,自引:2,他引:3
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J B Lefkowith M Kiehl J Rubenstein R DiValerio K Bernstein L Kahl R L Rubin M Gourley 《The Journal of clinical investigation》1996,98(6):1373-1380
We used an ELISA employing extracts of human glomerular basement membrane (GBM) to detect, characterize, and evaluate the clinical significance of glomerular-binding IgG in patients with SLE nephritis. Most patients with SLE nephritis exhibited GBM-binding IgG, although many patients with active nonrenal SLE or symptomatic, drug-induced lupus had similar reactivity, albeit at lower levels. IgG binding to GBM in SLE nephritis patients was decreased by DNase pretreatment of GBM, restored after DNase with nuclear antigens (most notably with nucleosomes), inhibited by exogenous nuclear antigens (particularly nucleosomes), but unaffected by exposure of serum to DNase/high ionic strength. The characteristics of IgG binding to GBM largely paralleled the patients' underlying autoimmune response, which was dominated either by antibodies to DNA/nucleosomes or to nucleosomes alone. Binding of lupus sera to nonrenal extracellular matrix (even with nucleosomes) was not equivalent to GBM. Collagenase pretreatment of GBM variably decreased IgG binding, depending on the level and type of binding. SLE nephritis patients with high levels of GBM-binding IgG exhibited more severe disease clinically, but the same renal histopathology, as patients with lower levels. The level of GBM-binding IgG at presentation did not predict the therapeutic response, but decreased in responders to therapy. In sum, glomerular-binding IgG in lupus nephritis binds to epitopes on chromatin, which adheres to GBM in part via collagen. These autoantibodies appear necessary, but not sufficient, for the development of nephritis, and correlate with clinical rather than histopathologic parameters of disease activity. 相似文献
20.
抗中性粒细胞胞浆抗体在系统性红斑狼疮伴有血管炎病变中的临床意义 总被引:1,自引:0,他引:1
目的探讨抗中性粒细胞胞浆抗体(ANCA)在系统性红斑狼疮(SLE)伴有血管炎病变中的临床意义。方法收集138例SLE住院病例的临床和实验室资料,间接免疫荧光(IIF)方法检测患者血清AN-CA,ANCA阳性者加做髓过氧物酶(MPO)、蛋白酶3(PR3)的酶联免疫检测(ELISA)。对患者进行SLEDAI评分评判疾病活动性,比较间接免疫荧光法检测ANCA阳性组与阴性组血管炎病变发生比率及疾病活动度有无差异。结果①间接免疫荧光法检测ANCA在SLE中的阳性率是15.2%,其中核周型ANCA阳性14.5%,胞浆型ANCA阳性0.7%;②SLE患者皮肤血管炎病变(包括面部红斑、结节红斑、雷诺现象、网状青斑、紫癜)发生率78.3%,肺间质病变(包括肺间质纤维化及出血性肺泡炎)发生率6.5%,肾脏病变(血尿及蛋白尿)发生率64.5%,ANCA阳性及ANCA阴性组SLE患者血管炎表现,包括皮肤血管炎(P=0.442)、肺间质病变(P=1.000)、肾脏病变(P=0.471)差异无统计学意义。③对所有SLE患者进行SLEDAI评分,ANCA阳性组及ANCA阴性组SLE活动性差异无统计学意义(P=0.879)。结论采用间接免疫荧光法检测ANCA的结果与SLE血管炎表现及病情活动无明显相关性。 相似文献