Gene/Protein Disease Symptom Drug Enzyme Compound
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 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pregnancy in patients with systemic lupus erythematosus (SLE) is considered a high-risk pregnancy. It is complicated by preeclampsia, premature labour and miscarriage more frequently than in the general population. Improved prognosis depends on low disease activity during conception and on appropriate medical care (SLE activity monitoring, selection of therapy safe for the mother and the developing foetus, advances in neonatology). Because symptoms of physiological pregnancy and SLE exacerbation are similar, their correct interpretation is essential for skin lesions, arthralgias, arterial hypertension or results of laboratory tests: proteinuria, thrombocytopenia or leucopenia observed in the patient. In order to standardise the assessment of SLE activity during pregnancy, scores of this activity are used. In the past, scores validated on non-pregnant populations (including male patients) were used: Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Systemic Lupus Activity Measure (SLAM), European Consensus Lupus Activity Measurment (ECLAM). Only recently have SLE activity scores been introduced that are specific for pregnant women: Lupus Activity Index In Pregnancy (LAI-P), Systemic Lupus Erythematosus Pregnancy Disease Activity Index (SLEPDAI), modified--Systemic Lupus Activity Measure (m-SLAM) and a visual three-grade score modified--Physician Global Assessment (m-PGA). So far, only scores LAI-P and m-PGA have been validated. According to the LAI-P score, clinical data are divided into 4 groups. Group 1 includes mild clinical symptoms, group 2--symptoms of involvement of internal organs, group 3 pertains to modifications of treatment and group 4 to laboratory parameters. Point values are ascribed to individual parameters depending on their intensity.
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PMID:[Evaluation of systemic lupus erythematosus activity during pregnancy]. 1796 97

Previous reports suggest a protective role for anti-La autoantibody against the development of lupus nephritis. We studied the effect of anti-La on the prevalence of nephritis in a large cohort of lupus patients. In addition, we determined the association between anti-La and the presence of the various other lupus manifestations. We studied 1100 lupus patients enrolled in the Lupus Family Registry and Repository. Only one lupus patient per family was selected to exclude intrafamilial correlation. Since anti-La is present in patients who also have anti-Ro autoantibody, we compared anti-Ro positive lupus patients in the presence or absence of anti-La. Clinical data were obtained from medical records, interviews and participant questionnaires. Tests for autoantibodies against extractable nuclear antigens were performed using immunodiffussion assays. There is no difference in the age, sex or race between the anti-La positive and anti-La negative lupus patients. The presence of anti-La is associated with a significant reduced risk of lupus nephritis (proteinuria: 29.3% versus 46.3%, OR = 0.48, P = 0.023; cellular casts: 8.6% versus 20.6%, OR = 0.36, P = 0.038). In addition, lupus patients with anti-La have a reduced risk for seizures (0% versus 10.9%, P = 0.0096) and are more likely to have arthritis (79.3% versus 64.0%, OR = 2.16, P = 0.031). The presence of anti-nRNP autoantibody is significantly reduced in anti-La positive compared with anti-La negative lupus patients (10.3% versus 27.4%, OR = 0.31, P = 0.0075). In conclusion, anti-La autoantibody is associated with less severe lupus. Patients with anti-La have a lower risk of renal involvement and seizures compared with anti-La negative lupus patients.
Lupus 2007
PMID:Presence of anti-La autoantibody is associated with a lower risk of nephritis and seizures in lupus patients. 1797 58

Polyomavirus BK (BKV) reactivation can occur in immunodeficient patients. Few studies on BKV infection in patients with systemic lupus erytematosus (SLE) nephritis are available. Aim of this study was to analyse the prevalence of BKV infection by quantifying viral load and to investigate the association with clinical and histological parameters indicating duration, type and activity of SLE.BKV-DNA was evaluated by polymerase chain reaction in serum (sBKV) and urine (uBKV) specimens from 40 patients with SLE nephritis and 29 healthy controls. Renal function, urinary activity, clinical index of SLE activity [SLE Disease Activity Index (SLEDAI) score], CD4+/CD8+ ratio, histological classes and duration of SLE nephritis were compared according to the BKV-DNA-positivity.sBKV was present in 15% of SLE patients and in 13.8% of controls; uBKV in 32% of SLE patients and in 17.2% of controls. There was no significant difference in terms of kidney function, urinary activity, SLEDAI score, presence of anti-dsDNA antibodies, CD4+/CD8+ ratio and BKV viremia and/viruria, as well as there was no significant correlation between SLEDAI score, anti-dsDNA antibodies titers and median viral load. Duration of nephropathy tended to be shorter in patients with BKV viremia and/or viruria; proteinuria/creatininuria ratio tended to be higher in patients with positive sBKV and uBKV. BKV-DNA-positivity tended to be more frequent in patients treated with an immunosuppressive agent versus those on steroid treatment. Reactivation of BKV infection can occur in patients with SLE, although prevalence data do not significantly differ from those obtained in the control group. The trend toward an association between BKV infection and degree of proteinuria and less duration of SLE nephritis could indicate a major susceptibility to develop BKV infection in more active phases of the disease. The role of BKV reactivation in terms of clinical parameters and histological pattern, as well as the role of therapeutic protocols in the onset of BKV reactivation and, conversely, the therapeutic implication of BKV reactivation in SLE patients remain to be defined and should be addressed in further studies on a larger number of patients.
Lupus 2007
PMID:Human polyomavirus BK in patients with lupus nephritis: clinical and histological correlations. 1797 61

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

TNF-like weak inducer of apoptosis (TWEAK), a member of the TNF superfamily, is a prominent inducer of proinflammatory cytokines in vitro and in vivo. We previously found that kidney cells display the TWEAK receptor Fn14, and that TWEAK stimulation of mesangial cells and podocytes induces a potent proinflammatory response. Several of the cytokines up-regulated in the kidney in response to TWEAK are instrumental in Lupus nephritis; we therefore hypothesized that TWEAK/Fn14 interactions may be important in the cascade(s) leading to renal damage in systemic Lupus erythematosus. In this study, we analyzed the effects of Fn14 deficiency in the chronic graft-vs-host model of SLE, and the benefits of treatment with an anti-TWEAK mAb in this mouse model. We found that anti-nuclear Ab titers were no different between C57BL/6 Fn14 wild-type and deficient mice injected with alloreactive bm12 splenocytes. However, kidney disease was significantly less severe in Fn14 knockout mice. Furthermore, kidney IgG deposition, IL-6, MCP-1, RANTES, and IP-10, as well as macrophage infiltration, were significantly decreased in Fn14-deficient mice with induced lupus. Similarly, mice with induced Lupus treated with an anti-TWEAK neutralizing mAb had significantly diminished kidney expression of IL-6, MCP-1, IL-10, as well as proteinuria, but similar autoantibody titers, as compared with control-treated mice. We conclude that TWEAK is an important mediator of kidney damage that acts by promoting local inflammatory events, but without impacting adaptive immunity in this experimental LN model. Thus, TWEAK blockade may be a novel therapeutic approach to reduce renal damage in SLE.
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PMID:TWEAK/Fn14 interactions are instrumental in the pathogenesis of nephritis in the chronic graft-versus-host model of systemic lupus erythematosus. 1802 43

The Phase III Aspreva Lupus Management Study (ALMS) will investigate mycophenolate mofetil (MMF) therapy for lupus nephritis (LN). Eligibility criteria include: 12-75 years of age; diagnosis of systemic lupus erythematosus according to revised American College of Rheumatology criteria; and biopsy-demonstrated LN (Class III-V). Randomized patients will receive open-label induction therapy with MMF or cyclophosphamide in combination with corticosteroids for 24 weeks. The primary efficacy endpoint is treatment response [decreased proteinuria and stabilized (within 25% of baseline) or improved serum creatinine level]. Patients achieving response or complete remission (normalization of all parameters) will be rerandomized to double-blind, placebo-controlled maintenance treatment with MMF or azathioprine, both plus corticosteroids. The maintenance phase primary endpoint is time to treatment failure. To detect a 15% rate improvement in the MMF group compared with cyclophosphamide, and to provide 90% power, a total of 358 patients will be required for the induction phase. On the basis of a projected 278 rerandomized patients, the maintenance phase will have 90% power to detect a difference between treatment groups assuming azathioprine and MMF three-year failure rates of 59.5% and 40.7%, respectively. Aspreva Lupus Management Study may provide invaluable comparative data on the efficacy and safety of MMF as LN induction and maintenance therapy.
Lupus 2007
PMID:Mycophenolate mofetil as induction and maintenance therapy for lupus nephritis: rationale and protocol for the randomized, controlled Aspreva Lupus Management Study (ALMS). 1804 91

Studies of immunosuppressive therapy, particularly mycophenolate mofetil (MMF), in membranous lupus nephritis (MLN) are limited. We report on our experience with primary (first-line) MMF therapy to induce and sustain renal remission in MLN with and without a concurrent proliferative lesion. Systemic lupus erythematosus (SLE) patients were studied, retrospectively, if treated with MMF for newly diagnosed MLN. Complete remission was defined as proteinuria less than 0.5 g/24 h, inactive urine sediment and normal estimated glomerular filtration rate. Response in pure MLN (Group I, n=10) was compared with mixed MLN and proliferative lupus nephritis (Group II, n=19). By 12 months, 4 (40%) patients in Group I and 7 (36.8%) in Group II achieved complete remission (P=0.87). One (10%) patient in Group I and 2 (10.5%) in Group II had worsening renal disease (P=0.97). Mean time to remission was more than seven months in both groups. The remaining patients had stable disease without improvement or worsening. Only 2 of 11 achieving initial remission had a relapse with an average of 28 months of follow-up after remission. Self-limited gastrointestinal symptoms occurred in 12 patients, none requiring withdrawal of the drug. Mycophenolate mofetil as a primary therapy in MLN was successful in inducing complete remission in about 40% of MLN, particularly in patients with mild proteinuria. However, 12 months of therapy was necessary for best outcomes. Response rate was not different in the presence or absence of a proliferative lesion.
Lupus 2008 Jan
PMID:Mycophenolate mofetil as the primary treatment of membranous lupus nephritis with and without concurrent proliferative disease: a retrospective study of 29 cases. 1808 82

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

To gain better understanding of systemic lupus erythematosus (SLE) in Dubai we studied the clinical and immunological manifestations in a cohort of 151 patients attended Rheumatology Clinic in Dubai Hospital between January 2002 and January 2007. We found that the female to male ratio was 20.5:1, with a mean age of 35.5 years (0.9). The mean age at disease onset was 28.9 years (0.8) and mean disease duration 6.7 years (0.4). Five-year survival rate in our cohort was 94%. The commonest clinical manifestations in this cohort were arthritis (88%), haematological abnormalities (61.6%), and malar rash (60.3%). Leucopenia, fever, hair loss and proteinuria were observed in approximately half of the patients. Anaemia was found in 44.3% but only 9.9% had haemolytic anaemia. Photosensitive rash was seen in 43% of patients. Approximately one-third of the patients had serositis and mouth ulcers, 30.5 and 27.2% respectively. Vasculitis was observed in 19.2% of patients. Neuropsychiatric manifestations (15.9%), discoid lupus lesions (12.6%), and brain infarcts (13.2%) were infrequent. Subacute cutaneous lupus (6%) was also uncommon. Anti-nuclear antibodies were detected in 98%, anti-double stranded DNA antibodies in 88.7%, anti-Sm antibodies in 19.7%, anti-RNP in 40.4%, anti-Ro antibodies in 52.3% and anti-La antibodies in 19.8%. Anti-cardiolipin IgM and IgG were detected in 25.3 and 22.4%, respectively. This study suggests that Arabs with SLE residing in Dubai have comparable clinical features to their counterparts in other Arab countries and Western countries. The high prevalence of positive anti-Ro antibodies among our Arab patients probably reflects a character, that is, commonly seen in SLE patients of Middle East origin.
Lupus 2008 Jan
PMID:Clinical and immunological manifestations in 151 SLE patients living in Dubai. 1808 86

C-reactive protein CRP is an acute-phase protein known as a biomarker for inflammation. As such CRP levels have been traditionally used to detect and predict the outcome of infections inflammatory and necrotic processes and to monitor the efficacy of treatment in these conditions. With the development of high sensitivity assays CRP has resurfaced as a very strong predictor in cardiovascular disease and as a mediator of atherosclerosis. The Centers for Disease Control and American Heart Association have elaborated guidelines for the use of CRP in the primary prevention setting and in patients with stable coronary disease or acute coronary syndromes. CRP has been used for differentiation between Systemic Lupus Erythematosus activity and infection in individuals without serositis. More recently CRP has also elicited interest as a therapeutic option in lupus. Murine lupus models treated with CRP have been reported to present delayed Lupus onset decreased antibody levels enhanced survival and reversal of ongoing proteinuria. In this paper we reviewed the multiple roles of CRP particularly in lupus.
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PMID:C-Reactive protein and its implications in systemic lupus erythematosus. 1815 97


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