Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disturbed apoptosis is proposed to be involved in the pathogenesis of systemic lupus erythematosus. However, the role of renal cell apoptosis in the pathogenesis and progression of human lupus nephritis is still controversial. We have investigated glomerular cell apoptosis and the clinicopathological relationship between apoptosis and immunoserological or histological findings in 22 patients with lupus nephritis using electron microscopy and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. Resident glomerular cells as well as infiltrating neutrophils undergoing apoptosis were observed in 12 of 20 patients with lupus nephritis using electron microscopy. TUNEL-positive cells were recognized in 93% of patients with diffuse proliferative lupus nephritis (class IV) in contrast to the 20% of patients with class V. The number of TUNEL-positive cells in glomeruli significantly correlated with the level of immunoserological activity of lupus, such as anti-double-stranded DNA autoantibody and consumption of plasma complement. There was a positive correlation between glomerular cell apoptosis and the degree of proliferation in lupus nephritis. These data suggest that apoptosis is increased, but not decreased in glomeruli from patients with lupus nephritis. The signals that could induce glomerular cell apoptosis in lupus nephritis will need to be identified.
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PMID:Glomerular cell apoptosis in human lupus nephritis. 1275 Aug 84

Renal biopsies of 69 patients with lupus nephritis were studied according to the WHO classification. The aim of the present study was to correlate the interstitial tryptase-positive mast cells with the interstitial TGF-beta1 and alpha-SM actin expression and clinical outcome of lupus nephritis, and identify the pathological role of the interstitial tryptase-positive mast cells in lupus nephritis. The mean follow-up time was 70.7 +/- 54.4 months. Eight patients were grouped as WHO class II lupus nephritis, 15 patients as class III, 28 patients as class IV and 18 patients as class V. Interstitial tryptase-positive mast cells were not correlated with clinical outcome and interstitial TGF-beta1 expression in lupus nephritis. Interstitial tryptase-positive mast cells were correlated with tubulo-interstitial alpha-SM actin expression for WHO class V lupus nephritis, but not to the other classes. In conclusion, in spite of interstitial tryptase-positive mast cells being related to renal interstitial fibrosis process, their expression according to the clinical outcome of lupus nephritis was not significant.
Lupus 2005
PMID:Mast cells, TGF-beta1 and myofibroblasts expression in lupus nephritis outcome. 1630 76

Mycophenolate mofetil (MMF) significantly reduces proteinuria in experimental model of human membranous nephropathy (Heymann nephritis). Twenty consecutive SLE patients with persistent isolated severe proteinuria and/or proteinuric flare were studied for 18 months of MMF therapy. All of them presented stable renal function and 12 had biopsy proven membranous glomerulonephritis (WHO class V). The starting daily dose for MMF was 1.5 g to a maximum of 3 g. Patients were divided into: partial response, >or=50% decrease of baseline proteinuria; complete response, normal proteinuria levels (less than 0.3 g/24 h); flare, increase of at least 50% of the mean baseline proteinuria. All 20 SLE patients (100%) presented a 50% reduction of baseline proteinuria which was achieved in 8.2+/-3.3 months of MMF therapy, at a mean daily dose of 2.3+/-0.5 g. A significant decrease in 24-h protein excretion was observed compared to entry (3.47+/-1.26 vs. 1.33+/-0.67 g, P<0.0001) as well as a correspondent increase of serum albumin (3.2+/-0.4 vs. 3.7+/-0.4 mg/dl, P=0.02) and reduction of prednisone dose (33.7+/-20.0 to 18.6+/-14.1 mg/day, P=0.01). Complete response was observed in 11 SLE patients (55%) in 12.2+/-3.0 months of therapy with a significant decrease in proteinuria (P<0.0001), prednisone dose (P<0.0001) and an increase of serum albumin (P=0.003). Interestingly, initial proteinuria or serum albumin levels did not identify patients with complete response and those with partial response at the end of the study (P=0.543 and 0.657, respectively). Our pilot prospective study suggests that MMF appears to be effective in reducing severe persistent proteinuria in lupus glomerulonephritis, even in patients unresponsive to other immunosuppressive treatments.
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PMID:Mycophenolate mofetil is effective in reducing lupus glomerulonephritis proteinuria. 1673 62

Human leukocyte antigens (HLA) DRB1*03 and DRB1*02 have been associated with systemic lupus erythematosus (SLE) in Caucasians and black populations. It has been observed that certain HLA alleles show stronger associations with SLE autoantibodies and clinical subsets, although they have rarely been associated with lupus renal histologic class. In the present study, HLA-DRB1 allele correlations with clinical features, autoantibodies and renal histologic class were analyzed in a cohort of racially mixed Brazilian patients with juvenile-onset SLE. HLA-DRB1 typing was carried out by polymerase chain reaction amplification with sequence-specific primers using genomic DNA from 55 children and adolescents fulfilling at least four of the American College of Rheumatology criteria for SLE. Significance was determined by the chi-square test applied to 2 x 2 tables. The HLA-DRB1*15 allele was most frequent in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, as well as in patients positive for anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, although an association between HLA alleles and SLE clinical features and autoantibodies could not be observed. The HLA-DRB1*17, HLA-DRB1*10, HLA-DRB1*15, and HLA-DRB1*07 alleles were significantly higher in patients with renal histologic class I, class IIA, class IIB, and class V, respectively. The present results suggest that the contribution of HLA- DRB1 alleles to juvenile-onset SLE could not be related to clinical or serological subsets of the disease, but it may be related to renal histologic classes, especially class I, class II A, class II B, and class V. The latter correlations have not been observed in literature.
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PMID:HLA-DRB1 alleles in juvenile-onset systemic lupus erythematosus: renal histologic class correlations. 1740 4

The objective of the current work is to report the preliminary experience with tacrolimus (TL) administered as a single-dose daily for maintenance therapy of young patients with pediatric-onset, long-standing systemic lupus erythematosus (SLE). Six consecutive patients with long-standing SLE were recruited for a 6-month open-label trial of single-dose-daily administration of tacrolimus (3 mg/day) without dose up of concomitantly administered prednisolone (PDN). TL treatment was started at the time of the most recent flares. Data on the clinical and serologic lupus activity were collected prospectively. The baseline characteristics of the patients were: mean age, 20 years; urinary protein/creatinine ratio, 1.22 +/- 1.94; serum C3 level, 70.8 +/- 21.2 (normal, 79-152 mg/dL); serum complement hemolytic activity (CH50), 22.2 +/- 10.3 (normal, 23-46 U/mL); serum anti-dsDNA antibody titer, 60.4 +/- 71.7 IU/mL (normal, < 12.0 IU/mL); serum creatinine, 0.55 +/- 0.11 mg/dL; European Consensus Lupus Activity Measurement (ECLAM) index, 5.2 +/- 2.6. Despite the gradual tapering of the PDN dose, marked improvement as compared with the baseline values was observed in the ECLAM index examined at one and three months and serological parameters examined at three months after the start of treatment. After a 6-months' therapy, complete response was achieved in all of the patients (serum CH50 value, 27.7 +/- 8.3 U/mL; serum anti-dsDNA antibody titer, 28.4 +/- 27.9 U/mL and the ECLAM index, 1.2 +/- 1.2 (P < 0.05), respectively), except in one patient who showed WHO class V lupus nephritis. No serious adverse effects were observed. These data suggest that TL, even when administered as a single-daily dose, is effective and safe for selected young patients with pediatric-onset, long-standing SLE. However, further studies on a larger number of patients are needed to confirm these results.
Lupus 2007
PMID:Effective treatment of young patients with pediatric-onset, long-standing lupus nephritis with tacrolimus given as a single daily dose: an open-label pilot study. 1797 63

Systemic Lupus Erythrematosus (SLE) is an inflammatory autoimmune disorder that may affect multiple organ systems. The clinical course is marked by spontaneous remission and relapses. Severity may vary from mild episodic disorder to a rapidly fulminant life threatening illness. Clinical manifestations of Lupus Nephritis (LN) are varied according to the renal pathologic lesions. Treatment of LN remains controversial. As a chronic disease with periods of remission and relapses, it is unclear whether relapses should be treated as the initial presentation of the disease. This prospective study was designed to compare between three different modalities of therapy for treating LN patients. The study includes all systemic lupus patients seen in Alexandria University Hospital since January 2004 for 6 months. Forty-three patients with SLE were presented to us by SLE, only 31 had LN and 22 were included in the study. The patients were classified randomly into 3 arms. All patients received steroid therapy plus from the beginning either Cyclophosphamide (CYP) [Group I, n=7], or Cyclosporine (CsA) [Group II, n=7], or Azathioprine (AZA) [Group III, n=8], Full history and examination were done. Laboratory investigations included routine and immunological studies of ANA, Anti-DNA, C3 and C4. Renal biopsy was done in all patients. After 6 months of follow up; Serum creatinine was stationary in CYP group from 2.2 +/- 1.1 to 2.1 +/- 1.7; while significantly decreased in CsA from 2.8+1.7 to 1.0 +/- 0.5 mg/dl. Moreover; while proteinuria decreased in CYP from 2.7 +/- 0.7 to 1.8 +/- 2.2; there was more pronounced decreased from 6.9 +/- 10.0 to 2.4 +/- 1.2 g/24 hr in CsA group despite very huge increase in glomerular filtration rate (GFR). 2 out 7 cases of CsA group; while 2 of 6 of CYP group did not show improvement. Moreover; 3 of 6 of CYP group and 1 of 6 of AZA group needed to be shifted to CsA group because of side effects and/or no response to CYP and showed good response. These patients were either class V or IV. However; only one case in this study with signs of acute CsA toxicity was reversed by monitoring the dose. In conclusion, CsA in this study proved to be superior over CYP in LN at least in the short term follow up; provided to be given with appropriate doses even if it is used in class IV, which was thought to be very responsive to CYP.
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PMID:Comparative clinical prospective therapeutic study between cyclophosphamide, cyclosporine and azathioprine in the treatment of lupus nephritis. 1797 49

A retrospective analysis of the long-term outcome of patients with membranous lupus nephropathy (MLN) was conducted. One hundred Chinese patients, 90 females and 10 males with a mean age of 32+/-9 years, with systemic lupus erythematosus and biopsy-proven MLN (ISN/RPS2003 classification criteria) were enrolled in this study. The patient and renal survivals were estimated by the Kaplan-Meier method and the risk factors associated with end-stage renal failure (ESRF) were assessed by the Cox proportional hazards regression analysis. The mean follow-up of all patients was 77.6+/-56 months. During follow-up, two patients died. Patient survival at 5 and 10 years was 98%. Renal survival at 5 and 10 years was 96.1% and 92.7%, respectively. Severe tubular-intersticial lesion (HR 66.514), nephrotic range proteinuria (HR 19.159) and refractoriness to treatments (HR 9.834) were independent risk factors for developing ESRF. Three of the six patients with ESRF had severe tubular-interstitial lesions on initial biopsy. Twenty-one patients underwent a repeat biopsy after 33months' (median time) follow-up, eight (38.1%) of these (class V superimposed class IV in 5, class V superimposed class III in 2 and class VI in 1) had transformed and three (37.5%) of them progressed to ESRF. Complications included infection (13%), thrombosis (3%), avascular necrosis (3%), diabetes mellitus (4%) and skin cancer (1%). The rate of patient and renal survival was high in this group of patients with MLN.
Lupus 2008 Jan
PMID:Long-term outcome of Chinese patients with membranous lupus nephropathy. 1808 85

Lupus nephritis is a common complication of systemic lupus erythematosus (SLE). Early recognition of lupus nephritis requires routine serum creatinine determination, urinalysis and urinary microscopy. Since mild urinary abnormalities such as leucocyturia or proteinuria can be associated with severe lupus nephritis, a renal biopsy is usually indicated in patients with SLE and urinary abnormalities. A renal biopsy is required to determine the class of lupus nephritis which is based on histopathological criteria which have recently been revised. Aggressive immunosuppressive therapy is indicated in diffuse proliferative lupus nephritis. In class III or class V the treatment indication depends on additional prognostic criteria. Intravenous cyclophosphamide is still used but doses and intervals have been modified based on large clinical trials. Mycopheno-late may establish as an alternative for cyclophosphamide in the induction phase, but the data of the transcontinental multicenter Aspreva Lupus Management Study (ALMS) trial have not yet been published in detail. Controlled clinical trials support the use of azathioprine and mycophenolate for maintaining remission of lupus nephritis, and cyclophosphamide is no longer used in that phase. Additional control of cardiovascular risk factors and combined angiotensin and angiotensin receptor blockade are mandatory for all proteinuric SLE patients. Novel treatment options are ahead of us based on the molecular mechanisms of SLE and lupus nephritis, but as evidence from controlled clincial trials is still lacking they are not yet approved for broad clinical use. However, the treatment options for severe lupus nephritis have been improved and are likely to further improve in the near future.
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PMID:Lupus nephritis. 1829 86

Recently a role of the upregulation ofcyclooxygenase isoforms in renal injury and modulation the severity of the inflammatory reactions is suggested. Cyclooxygenase exists as two isoforms COX-1 and COX-2 which are poorly understood with regard to their roles in renal function. Thereby, the present study was undertaken to ascertain the immunoexpression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in lupus (LMGN) and nonlupus (NLMGN) membranous glomerulopathy and to examine the possible relationship between this immunoexpresion and inflammatory infiltrates. Eleven renal biopsy specimens from patients with class V lupus glomerulopathy and 16 from patients with primary (nonlupus) membranous glomerulopathy were examined by percutaneous renal biopsy. As a control 10 biopsy specimens of the kidneys removed because of trauma were used. In each specimen staining intensity of COX-1 and COX-2 in glomeruli, tubuli, arterioles and interstitial cells were recorded semiquantitatively whereas CD68+ cells, CD3+ cells and CD20+ cells were assessed quantitatively using computer image analysis system. Our study revealed that the mean scores of COX-1 immunoexpression did not differ significantly in all groups investigated whereas immunoexpression of COX-2 in LMGN was significantly stronger as compared with both NLMGN and controls. Moreover, in LMGN a significant positive relationship was noted between COX-2 immunoexpression and CD 68+ cells. In NLMGN and controls the correlations between COX-2 immunoexpression and CD 68+ cells were positive, but they have not reached statistical significance. In conclusion, our findings point that glomerular inflammation in lupus and non-lupus membranous glomerulopathy have different signalling pathways and suggest that in lupus nephritis COX-2 and monocytes/ macrophages but not COX-1 isoform are involved in the inflammatory process.
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PMID:Analysis of renal immunoexpression of cyclooxygenase-1 and cyclooxygenase-2 in lupus and nonlupus membranous glomerulopathy. 1845 55

This study aimed to analyze the clinicopathological characteristics of familial SLE patients with lupus nephritis (LN). A total of 136 Chinese patients with lupus nephritis diagnosed by renal biopsy, including 34 familial patients and 102 sporadic cases, were recruited. Their demographic information, age of onset, disease duration, clinical features, laboratory data and histological manifestations were compared. The first-degree relatives (17 sibling cases and eight parent-offspring cases) of familial SLE patients were primarily affected. The prevalence of fever, rash and arthritis in familial subjects was higher than that in sporadic subjects. Familial patients had lower platelet counts and higher low-density lipoprotein. In familial patients, class V lupus nephritis was less common. After adjusted with the Benjamini and Hochberg procedure, however, fever was the only feature occurring significantly and more frequently in familial patients (58.8% vs 26.5%, P = 0.001). Moreover, SLEDAI and other clinicopathological features did not differ significantly between the two groups. Multivariate analysis showed that a higher prevalence of fever was an independent predictor of familial SLE. Most clinicopathological features in familial SLE patients were not significantly different from those in sporadic patients; the severity of LN in familial SLE patients was similar to that of sporadic cases. Thus, familial SLE may not be a different clinical entity.
Lupus 2009 Mar
PMID:Clinicopathological characteristics of familial SLE patients with lupus nephritis. 1921 63


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