Silent nephritis in systemic lupus erythematosus

Silent lupus nephritis (SLN) was investigated in 42 renal asymptomatic patients and compared with 49 untreated patients with overt lupus nephropathy (OLN). Urinary sediment, quantitative proteinuria, creatinine clearance, antinuclear antibodies (ANA), complement, circulating immune complexes (CIC) and renal biopsies were evaluated in all of the patients. Forty-one out of the 42 (97.6%) patients had SLN according to histopathological findings. Results showed that the mean age, female/male ratio and the clinical activity index (SLEDAI) were similar in both groups (P > 0.05). The prevalence of ANA, anti-ds DNA, anti-ENA autoantibodies and C4 serum levels showed no statistical differences between the two groups (P > 0.05). Conversely, in the OLN group, elevated CIC and diminished CH50 and C3 serum levels were significantly different (P < 0.01). WHO class II was the predominant renal lesion in the group with SLN (P < 0.0001), whereas class IV was in the OLN patients (P < 0.0001). We conclude that, in our series, SLN was highly prevalent in renal asymptomatic patients with otherwise systemic lupus erythematosus. Furthermore, abnormal levels of CIC, CH50 and C3 associated with WHO class II suggest a moderate but ongoing activation of immune-mediated renal injury mechanisms.     

Intercellular adhesion molecules in systemic lupus erythematosus patients with lupus nephritis

Cardiovascular events are markedly increased in systemic lupus erythematosus (SLE), and the mechanism of atherogenesis remains poorly understood. Several methods have been employed to assess endothelial function, among these is the measurement of biomarkers of endothelial activation and dysfunction [intercellular adhesion molecule (ICAM-1)]. It has been reported that such biomarkers play a more important role than traditional risk factors in cardiovascular disease. The objectives of this study were to determine the level of ICAM-1 as markers of endothelial dysfunction in 40 Egyptian patients who have SLE with various degrees of activity and to investigate their relationship to disease activity. Sixty people (40 with SLE and 20 healthy as the control group) were the subject of this study; their clinical disease activity was scored according to the SLE disease activity index (SLEDAI), and serum sampling was obtained for ICAM-1 level assay. Renal biopsy was carried out and examined by light microscopy by a pathologist blinded to the clinical activity. The mean level of ICAM-1 was significantly higher in SLE patients with active disease (826.05 ± 367.1 Pg/ml) compared to those with inactive disease (441.33 ± 225.19 Pg/ml) and the healthy control volunteers (111.5 ± 17.36 Pg/ml). There was a positive correlation between serum ICAM-1 and SLEDAI (r = 0.66). A high concentration of soluble ICAM-1 in SLE patients with nephritis is reported in this paper. Our finding of increased concentrations of ICAM-1 in SLE patients with nephritis underlines the importance of inflammation and endothelial involvement in this disease, but their predictive value in the disease monitoring need to be further studied.     

Arthritis and nephritis in patients with systemic lupus erythematosus

Previous publications suggest that in patients with systemic lupus erythematosus (SLE), rheumatoid factor (RF) may be "protective" against nephritis. In our study of 662 patients with SLE, we found that persistent, rheumatoid-like arthritis showed a much stronger inverse correlation with nephritis than RF. Of 186 such patients, 59 developed clinically evident nephritis (32%) compared to 263 of the other 476 patients (55%) (p less than 10(-7). RF showed only a weak inverse relationship to nephritis (p = 0.064). We conclude that the presence of persistent rheumatoid-like arthritis in patients with SLE identifies a clinical subset of patients who are less likely to develop nephritis than those with no arthralgia, no objective arthritis or only episodic arthritis. We hypothesize that such patients represent a genetically determined subset among patients with SLE and that perhaps they are more likely to bear the HLA-DR4 allele.     

Association of serum nitrate and nitrite levels with longitudinal assessments of disease activity and damage in systemic lupus erythematosus and lupus nephritis

OBJECTIVE: Reactive intermediate production is an essential component of the innate immune response that is induced during disease activity in murine lupus. This study was undertaken to determine whether a marker of systemic nitric oxide (NO) production correlates with prospectively studied disease activity in human systemic lupus erythematosus (SLE) and lupus nephritis patients. METHODS: Eighty-three SLE patients and 40 control subjects were studied longitudinally. The SLE group included 23 patients with lupus nephritis documented by renal biopsy and 26 with a history of lupus nephritis. During each visit, following a 24-hour low-nitrate diet, traditional markers of disease activity and damage were determined. Serum nitrate plus nitrite (NOx) levels were determined by chemiluminescence detection. RESULTS: NOx levels were higher in SLE patients than in controls during the first visit. In univariate longitudinal analyses, NOx levels were associated with SLE Disease Activity Index scores. In multivariate analyses, NOx levels were associated with serum levels of C3 and creatinine and the urinary protein:creatinine ratio. Among patients with lupus nephritis, those with proliferative lesions had higher NOx levels, and higher NOx levels were associated with accumulation of renal damage and lack of response to therapy. CONCLUSION: This is the first study to prospectively demonstrate longitudinal associations between serum NOx levels and markers of SLE and lupus nephritis disease activity. The more pronounced association with proliferative lupus nephritis and with longitudinal response to lupus nephritis therapy provides a rationale for the study of reactive intermediates as biomarkers of disease activity and therapeutic targets in proliferative lupus nephritis.     

Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus

OBJECTIVE: To study 5 type I interferon (IFN)-inducible genes (LY6E, OAS1, OASL, MX1, and ISG15) in patients with systemic lupus erythematosus (SLE) and to correlate expression levels with disease activity and/or clinical manifestations. METHODS: Peripheral blood cells were obtained from 48 SLE patients, 48 normal controls, and 22 rheumatic disease controls, and total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real-time polymerase chain reaction, standardized to a housekeeping gene, and summed to an IFN score. Disease activity was determined by the Safety of Estrogens in Lupus Erythematosus: National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) composite. RESULTS: Each gene was highly expressed in SLE patients compared with normal controls (P < or = 0.0003) or disease controls (P < or = 0.0008 except for MX1). IFN scores were positively associated with the SELENA-SLEDAI instrument score (P = 0.001), the SELENA-SLEDAI flare score (P = 0.03), and the physician's global assessment score (P = 0.005). Compared with patients without nephritis, lupus nephritis patients had higher IFN scores (overall P < 0.0001), especially during active renal disease. IFN scores were weakly associated with neurologic manifestations. Elevated IFN scores were positively associated with the current presence of anti-double-stranded DNA (anti-dsDNA) antibodies (P = 0.007) or hypocomplementemia (P = 0.007). LY6E expression levels distinguished active from inactive lupus nephritis (P = 0.02) and were positively associated with proteinuria (P = 0.009). CONCLUSION: The 5 IFN-inducible genes were highly expressed in SLE patients, and increased levels were correlated with disease activity defined by several methods. IFN scores, or LY6E levels, were elevated in lupus nephritis patients, especially during active renal disease, and in patients with anti-dsDNA antibody positivity and hypocomplementemia. IFN scores, or LY6E levels, may be useful as a biomarker for lupus nephritis therapy.     

Illness perceptions in patients with systemic lupus erythematosus and proliferative lupus nephritis

This study investigated the illness perceptions of patients with systemic lupus erythematosus (SLE) and whether perceptions are influenced by type of treatment for proliferative lupus nephritis. In addition, the illness perceptions of SLE patients were compared with those of patients with other chronic illnesses. Thirty-two patients who had experienced at least one episode of proliferative lupus nephritis were included. Patients were treated with either a high or low-dose cyclophosphamide (CYC) regimen (National Institutes of Health [NIH] vs. Euro-Lupus protocol). Illness perceptions were measured with the Brief Illness Perception Questionnaire (B-IPQ) and a drawing assignment. The low-dose CYC group perceived their treatment as more helpful than the high-dose CYC group. In comparison with patients with asthma, SLE patients showed more negative illness perceptions on five of the eight illness perception domains. Drawings of the kidney provided additional information about perceptions of treatment effectiveness, kidney function and patients' understanding of their illness. Drawing characteristics showed associations with perceptions of consequences, identity, concern and personal control. These findings suggest that the type of treatment SLE patients with proliferative lupus nephritis receive may influence perceptions of treatment effectiveness. In addition, patients' drawings reveal perceptions of damage caused by lupus nephritis to the kidneys and the extent of relief provided by treatment. The finding that SLE is experienced as a more severe illness than other chronic illnesses supports the need to more frequently assess and aim to improve psychological functioning in SLE patients.     

Associations of serum urea, creatinine and uric acid with clinical and laboratory features in patients with systemic lupus erythematosus

The aim of this study is to investigate the associations of serum urea, creatinine and uric acid levels with clinical and laboratory characteristics, independent of lupus renal involvement in SLE patients. A total of 191 SLE patients were included in the present study. Some clinical and laboratory characteristics of the patients were obtained by medical record review. The results showed that serum urea, creatinine and uric acid levels seemed to be associated with several clinical and laboratory characteristics of SLE. However, multivariate logistical regression analysis indicated that increasing serum urea levels were positively associated with disease duration and thrombocytopenia, but negatively with arthritis and skin rash. Compared with quartile 1 of urea, the ORs of quartile 2, quartile 3 and quartile 4 were, respectively, 1.008 (0.997–1.015, P?=?0.189), 1.010 (1.001–1.019, P?=?0.038) and 1.014 (1.004–1.024, P?=?0.008) with increasing disease duration; 1.912 (0.516–7.088, P?=?0.332), 10.126 (2.771–36.997, P?=?0.000) and 5.583 (1.285–24.266, P?=?0.022) with thrombocytopenia; 0.864 (0.331–2.254, P?=?0.765), 0.516 (0.18–1.475, P?=?0.217) and 0.162 (0.047–0.557, P?=?0.004) with arthritis; and 0.342 (0.135–0.868, P?=?0.024), 0.215 (0.074–0.622, P?=?0.005) and 0.332 (0.097–1.13, P?=?0.078) with skin rash. Increasing serum creatinine levels were positively associated with sex, disease duration and SLEDAI, but negatively with skin rash. Compared with quartile 1 of creatinine, the ORs of quartile 2, quartile 3 and quartile 4 were, respectively, 2.993 (0.282–31.74, P?=?0.363), 7.937 (0.861–73.18, P?=?0.068) and 13.411 (1.32–36.246, P?=?0.028) with male, 1.011 (1.002–1.02, P?=?0.017), 1.002 (0.991–1.013, P?=?0.684) and 1.018 (1.008–1.028, P?=?0.001) with increasing disease duration; 1.112 (1.006–1.228, P?=?0.038), 1.065 (0.959–1.183, P?=?0.239) and 1.140 (1.022–1.272, P?=?0.019) with increasing SLEDAI; and 0.303 (0.119–0.771, P?=?0.012), 0.282 (0.104–0.76, P?=?0.012) and 0.174 (0.052–0.584, P?=?0.005) with skin rash. Increasing serum uric acid levels were only positively associated with erythrocytopenia. Compared with quartile 1 of uric acid, the ORs of quartile 2, quartile 3 and quartile 4 were, respectively, 0.910 (0.37–2.239, P?=?0.837), 2.147 (0.901–5.116, P?=?0.085) and 3.079 (1.211–7.828, P?=?0.018) with erythrocytopenia. The present study demonstrated that, except for reflecting renal function, serum urea, creatinine and uric acid exert separate clinical significances in SLE.     

Differential activation mechanisms of serum C5a in lupus nephritis and neuropsychiatric systemic lupus erythematosus

Objective: To explore the role of C5a in the pathogenesis of neuropsychiatric systemic lupus erythematosus (NPSLE) and lupus nephritis (LN).

Methods: Sera were obtained from 29 patients with NPSLE, 25 with LN, 26 without NPSLE or LN [SLE alone], and 21 healthy donors. Cerebrospinal fluid (CSF) was obtained from 29 NPSLE patients. C5a and C5 were measured by ELISA. Blood-brain barrier (BBB) function was evaluated by Q albumin ([CSF albumin/serum albumin]?×?10³).

Results: Serum C5a, but not C5, was significantly increased in SLE compared with healthy control. Serum C5a, but not C5, was significantly higher in NPSLE and in LN than in SLE alone. Serum C4, but not C3, was lower in LN than in NPSLE. Q albumin was significantly higher in diffuse NPSLE than in focal NPSLE, whereas there were no significant differences in CSF or serum C5a between both groups. Notably, CSF C5 and C5a were significantly correlated with Q albumin, whereas serum C5a, but not C5, appeared to be inversely correlated with Q albumin.

Conclusion: These results disclosed that serum C5a was elevated not only in NPSLE but also in LN through different mechanisms. Moreover, it is suggested that C5a might be consumed during BBB damages.     

Pathogenesis and treatment of systemic lupus erythematosus nephritis

PURPOSE OF REVIEW: Glomerulonephritis is a challenging complication of systemic lupus erythematosus that still results in kidney loss in up to 30% of patients. In this review we highlight the development of integrated efforts to link pathogenesis with disease definition and new therapeutics. RECENT FINDINGS: Immune complex deposition in the kidney initiates an inflammatory cascade that causes glomerular disease but there are many modulating factors including genetic predisposition, products of the innate immune system, cytokines, complement and activated cells (both renal and immune). Animal models can help dissect potential disease mechanisms but the study of multiple models will be required since there are multiple subsets of human disease. Recent therapeutic studies in humans address the distinction between therapies for remission induction and remission maintenance. Multiple studies confirm the therapeutic equivalence of mycophenolate mofetil and cyclophosphamide in induction of remission but results are still far from ideal. The next few years should see the testing of new biologic reagents in humans. Another area of interest is the search for noninvasive measures of disease and disease response. SUMMARY: Although there has been remarkable progress in our understanding of the immunology and phenotype of lupus nephritis current therapies have insufficient efficacy. As new therapies emerge, improved clinical design coupled with mechanistic studies will be needed to identify agents that may be effective only in some patient subpopulations.     

系统性红斑狼疮与人类白细胞抗原-Cw基因相关性的研究

目的 探讨系统性红斑狼疮(SLE)与人类白细胞抗原(HLA)-Cw等位基因的相关性.方法 应用聚合酶链反应-序列特异性引物(PCR-SSP)的方法对108例SLE患者和102名健康人HLA-Cw01-08等位基因进行检测,比较两组间各等位基因的基因表型频率分布差异.结果 SLE患者组中HLA-Cw07的基因表型频率高于对照组,差异有统计学意义.结论 HLA-Cw07可能是SLE的易感基因或易感连锁基因.     

Reversible posterior encephalopathy syndrome in systemic lupus erythematosus and lupus nephritis

Reversible posterior encephalopathy syndrome (RPES) is a clinical entity characterized with headache, nausea, vomiting, seizures, consciousness disturbance, and frequently visual disorders associated with neuroradiological findings, predominantly white matter abnormalities of the parieto-occipital lobes. The central nervous system manifestations of systemic lupus erythematosus (SLE) are highly diverse. However, SLE-associated RPES has been seldom reported. Here, we report a case with RPES in SLE and lupus nephritis with exclusive involvement of parietal and occipital cortices. A systematic review of the literature on the pathogenesis and treatment of SLE-associated RPES is included.     

Complement activation in patients with systemic lupus erythematosus without nephritis.

OBJECTIVE: To study the association between disease activity and complement activation prospectively in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Twenty-one SLE patients were examined monthly for 1 yr. Disease activity, autoantibodies, conventional complement tests and the following complement activation products were investigated: C1rs-C1inh complexes, C4bc, Bb, C3a, C3bc, C5a and the terminal SC5b-9 complement complex (TCC). RESULTS: Modest variation in disease activity was noted. None of the patients had nephritis. Flare was observed at 27 visits. Four patients had anti-C1q antibodies in conjunction with modestly low C1q concentrations. The complement parameters were rather constant during the observation period. Slightly to moderately decreased C4 (0.05-0.10 g/l) was found in 10 patients and severely decreased C4 (<0.05 g/l) in seven patients. Decreased C4 was not associated with increased complement activation. Complement activation products were either normal or slightly elevated. TCC was the only activation product correlating significantly with score for disease activity at flare. None of the variables tested predicted flares. CONCLUSION: Complement tests are of limited importance in routine examination of SLE without nephritis, although TCC is suggested to be one of the most sensitive markers for disease activity.     

Environmental factors predicting nephritis in systemic lupus erythematosus.

OBJECTIVES--To evaluate social class, ethnic origin, and various endocrine variables as potential risk factors in the development of nephritis in patients with systemic lupus erythematosus (SLE). METHODS--A cross-sectional survey was carried out of all outpatients with SLE attending the lupus Clinic of St Thomas's Hospital from March to October 1992 using retrospective survival data. The main outcome measure was the duration of SLE before the onset of nephritis. RESULTS--Two hundred and ninety six women and 11 men were studied; the male patients were excluded from the analysis. Univariate analysis showed an increased risk of nephritis in patients with SLE of West Indian origin with 54 v 19% with nephritis at five years, in patients of lower social class, in patients who did not drink alcohol, and in those with a history of fetal loss after the onset of lupus. No significant effect of the age of onset of SLE, use of oral contraceptives, normal pregnancy, or smoking was seen. Multivariate analysis showed that ethnic origin did not influence the risk of nephritis independently of social class. CONCLUSIONS--Factors associated with socioeconomic deprivation may increase disease severity in patients with SLE.