抗核小体抗体与抗C1q抗体在狼疮肾炎血清的表达及其临床意义

目的探讨抗核小体抗体与抗C1q抗体在狼疮肾炎（lupus nephritis，LN）患者血清的表达及其临床意义。方法使用酶联免疫吸附试验（ELISA）对46例LN患者血清进行检测，并与31例无肾炎临床表现的SLE患者作对照。结果LN患者血清中抗核小体抗体与抗C1q抗体浓度及阳性率显著高于SLE对照组（P〈0．01）。抗双链DNA（dsDNA）抗体、抗Sm抗体、抗nRNP抗体、抗心磷脂（aCL）IgG抗体有较高的阳性率，与对照组相比差异有统计学意义（P〈0．05）。将抗核小体抗体、抗C1q抗体、抗dsDNA抗体、抗Sm抗体、抗nRNP抗体和aCLIgG抗体分别引入Logistic回归进行统计分析，结果显示入选的自变量包括抗核小体抗体、抗C1q抗体、抗dsDNA抗体（P〈0．05）。结论在LN患者中，存在着抗核小体抗体、抗C1q抗体的高表达。抗核小体抗体及抗C1q抗体在LN发病中起重要的作用。抗核小体抗体、抗C1q抗体、抗dsDNA抗体是反映SLE患者并发肾脏损害的重要指标，在LN诊断和判定其活动性方面有重要作用。     

Role of syndecan-1 (CD138) in Egyptian systemic lupus erythematosus patients with lupus nephritis: Relation to disease activity

BackgroundSyndecan-1, a transmemebrane heparan-sulfate glycoprotein, is predominantly expressed by plasma cells and is readily shed and released under certain pathologic conditions and remains biologically active to plasma cells behaviour.Aim of the workTo assess the level of syndecan-1 in relation to lupus nephritis (LN) and systemic lupus erythematosus (SLE) activity.Patients and methodsThe study included 60 SLE patients subgrouped according to the presence of LN and activity. SLE disease activity index (SLEDAI) was assessed. Serum syndecan-1 level was measured.ResultsThe patients mean age was 25.9 ± 8.6 years, they were 54 females and 6 males with a disease duration of 3.8 ± 3.4 years. There was a significant difference in the level of syndecan-1 between healthy control (46.3 ± 12.2 ng/ml) and SLE patients whether they were with active LN (150.2 ± 31.1 ng/ml) (p < 0.001), extrarenal flare (86.9 ± 16.7 ng/ml) (p < 0.001) or inactive (79.1 ± 19.8 ng/ml) (p < 0.003). Syndecan-1 was significantly higher in patients with active LN compared to those with extrarenal flare and inactive disease (p < 0.001 and p < 0.001 respectively). Serum syndecan-1 level was significantly higher in patients with arthralgia, arthritis, pleurisy and pericarditis) (all p < 0.001). There was a significant correlation between syndecan-1 level and 24 h urinary proteins (r = 0.8, p < 0.0001), and inversely with the complement (C3: r = −0.54, p < 0.0001 and C4: r = −0.48, p < 0.0001). There was a significant correlation between syndecan-1 and SLEDAI (r = 0.68, p < 0.001).ConclusionSerum syndecan-1 is significantly high in active LN patients and can be a useful tool for diagnosis of active nephritis. It correlates with disease activity, consumed complement and proteinuria. It was significantly related to the presence of musculoskeletal manifestations and serositis.     

Juvenile lupus: Different clinical and serological presentations compared to adult lupus in Egypt

Aim of the work: We aimed to evaluate the differences in clinical presentation, serological pattern and disease activity between juvenile and adult-onset of Egyptian systemic lupus erythematosus (SLE) patients. Patients and methods: 160 Egyptian SLE patients (80 Adult-onset and 80 juveniles) were included. Patients records were reviewed for clinical and laboratory evaluation on presentation. Disease activity at onset was assessed using SLE Disease Activity Index (SLEDAI). Results: The mean age of the adult patients was 29.9 ± 7.2 years and of the juvenile cases (12.8 ± 2.1 years). The female:male ratio of the adults was 10:1 while it was 39:1 in the SLE children. The most common clinical presentation among adult SLE was malar rash (75%) followed by articular manifestations (62.5%), while in juveniles, nephritis (78.8%) followed by articular manifestations (71.2%) were the most common. Juvenile patients had more frequent neuropsychiatric (p = 0.015) and hematologic abnormalities (p < 0.001) at onset; and lupus nephritis (72.5%) compared to adults (36.2%) (p < 0.001) during the first year of presentation. Juvenile SLE showed higher frequency of proteinuria (p < 0.001), hematuria (p = 0.02) and active urinary sediments (p = 0.016). Proliferative nephritis was the most common form among both juveniles and adults. Positivity and titres of both anticardiolipin antibodies and lupus anticoagulant were significantly higher in juvenile SLE. Juvenile SLE patients had significantly higher SLEDAI [median (IQR): 12 (10–22)] compared to adults [median (IQR): 8 (4–12)], p < 0.001. Conclusion: Juvenile SLE patients differ from adult SLE with more frequent major organs affection and significantly higher serological activity. Earlier and more careful assessment with strict management plan and follow-up are needed in juvenile SLE patients.     

Endothelial cell-binding antibodies in patients with systemic lupus erythematosus

 The implications of endothelial cell-binding IgG antibodies (EC IgG) in systemic lupus erythematosus (SLE) was evaluated by determining level of EC IgG in sera from 112 SLE patients. The serum EC IgG level was determined by the cyto-ELISA method using human umbilical vein endothelial cells (HUVEC), human microvascular endothelial cells (HMVEC), and aortic endothelial cells (HAEC) as antigens. The levels of EC IgG were significantly higher among patients with SLE than among healthy control subjects (P < 0.001), and 68% (76/112) of SLE patients were shown to be EC IgG-positive. In patients with active lupus nephritis, the level of EC IgG was statistically and significantly elevated compared with those without lupus nephritis (P < 0.05). Negative correlations between EC IgG level and levels of CH50, C3, and lymphocyte count were revealed (P < 0.05, P < 0.005, and P < 0.05, respectively). When clinical course was evaluated, the levels of EC IgG correlated with disease activity. Definitive correlations in antibody levels between HUVEC and HMVEC, and between HUVEC and HAEC were revealed (both P < 0.0001). The results of this study revealed that the EC IgG in patients with SLE was involved in the onset of clinical manifestation, especially in patients with active lupus nephritis. Received: January 28, 2002 / Accepted: July 12, 2002 Acknowledgments This investigation was supported by grants from the Research Committee on Intractable Vasculitides, and the Ministry of Health and Welfare of Japan, from 1996 to 2000. Correspondence to:H. Bando     

Liver fatty acid binding protein: A potential urinary and tissue biomarker for lupus nephritis

Aim of the work

To assess urinary liver fatty acid binding protein (uL-FABP) levels and tissue expression (tL-FABP) in renal biopsies of active and inactive lupus nephritis (LN) patients and examine their relationship with disease characteristics.

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.     

Serum ferritin level as a marker of disease activity and renal involvement in Egyptian children with juvenile systemic lupus erythematosus

Introduction

Ferritin is an acute-phase reactant that is elevated in several autoimmune disorders. Serum ferritin levels have been correlated with disease activity scores of juvenile systemic lupus erythematosus (JSLE). Furthermore, enhanced levels of ferritin have also been described in lupus nephritis (LN).

Anti-nucleosome antibodies in systemic lupus erythematosus patients: Relation to anti-double stranded deoxyribonucleic acid and disease activity

Aim of the work

To measure the level of anti-nucleosome (anti-NCS) antibodies in systemic lupus erythematosus (SLE) patients and to evaluate their relation with anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies and SLE disease activity.

Lymphopenia and systemic lupus erythematosus,a preliminary study: Correlation with clinical manifestations,disease activity and damage indices

IntroductionSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by excessive autoantibody production against ‘self’ antigens and immunocomplex formation, resulting in frequent widespread inflammatory damage to target multiple organ systems.Aim of workTo determine the association of lymphopenia with the clinical manifestations, serologic abnormalities, disease activity and disease damage as well as drug intake in SLE patients.Patients and methodsThe present study was carried out on forty-five SLE female patients fulfilling the American College of Rheumatology (ACR) revised criteria for the diagnosis of SLE. They were divided into two groups according to the lymphocytes’ count: Group-I: thirty patients with lymphopenia (<1500/mm³) and group-II: fifteen patients without lymphopenia (⩾1500/mm³). Ten healthy age matched females (group-III) taken as a control group. Patients and control groups were recruited from the Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University Hospitals. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Disease damage was assessed with Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index.ResultsLymphopenia in patients with SLE was found to be associated with lupus nephritis (p = 0.023), leucopenia (p = 0.004), increased disease activity index (p = 0.03) and increased organ damage index (p = 0.02), and was not associated with other clinical lupus manifestations, serological abnormalities or with the drug intake (p > 0.05).ConclusionLymphopenia in SLE was associated with lupus nephritis, leucopenia and increased both disease activity and organ damage indices.     

The utility of lupus serology in predicting outcomes of renal transplantation in lupus patients: Systematic literature review and analysis of the Toronto lupus cohort

ObjectivesTo study the utility of lupus serology as a predictor for kidney graft outcome in (a) a systematic literature review (SLR) and (b) the Toronto lupus cohort (TLC).MethodsFor the SLR, a comprehensive literature search was performed to identify the articles reporting on the serology at renal transplantation (RT) and on the outcome of RT. Studies were critically appraised using the Newcastle Ottawa Scale (NOS). Patients who underwent RT in the TLC were identified and grouped into graft failure and graft survival. The serology in both groups was studied.ResultsOf the 749 references, 742 did not have serological status of the patient or were not relevant to the research question. Seven studies in addition to TLC (n = 76) were included in the SLR. The NOS revealed limitations because of small sample size and a short follow-up period. The majority of the grafts survived to at least 1 year regardless of the serology results pre-transplant which is consistent with results of the TLC. Overall, 32 of 1783 patients in the TLC had a RT. In all, 2 patients had a nonfunctional graft, 5 patients had graft failure, and 25 patients had graft survival. Overall, 40% of the graft failures had positive serology compared to 52% in the graft survival, 1 year prior to RT.ConclusionThe results of this SLR found that the persistence of serological abnormalities at the time of RT was not associated with graft failure. These results are consistent with the results of the TLC.     

IgM anti-dsDNA antibodies in systemic lupus erythematosus: negative association with nephritis

Antibodies against dsDNA of the IgM class were measured in sera of 352 patients with systemic lupus erythematosus, 81 blood donors and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgM anti-dsDNA antibodies were found in 52.3% of the sera from patients with systemic lupus erythematosus, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 37 laboratory parameters was calculated. There was a highly significant negative correlation between IgM anti-dsDNA antibodies and nephritis as well as all the laboratory parameters indicating renal disease (elevated serum creatinine concentration, proteinuria, erythrocyte casts in the urine). IgM anti-dsDNA antibodies indicate protection of lupus patients against the development of lupus nephritis. Further experiments will show whether application of IgM anti-dsDNA antibodies is effective in treating lupus nephritis. Received: 10 August 1998 / Accepted: 11 September 1998     

Multicenter cooperative study of HLA class II alleles in Japanese patients with systemic lupus erythematosus

The relation between HLA class II alleles and clinical findings were examined in Japanese patients with systemic lupus erythematosus (SLE). In 284 patients with multicenter SLE, HLA class II alleles were examined using the DNA typing method, and the results were compared with the clinical findings. The frequency of DRB1^*0101 and DQB1^*0501 significantly increased in male patients, and that of DRB1^*0803 significantly increased in patients over 50 years of age. In relation to cutaneous manifestations, there were positive photosensitivity associations with DQA1^*0101 and/or DQA1^*0301, malar rash with DQA1^*0101 and/or DRB1^*0901, alopecia with DQA1^*0101, skin ulcers with DRB1^*0401, and oral ulcers with DQA1^*0301. In addition, there were also positive associations of myalgia with DRB1^*1406 and negative associations of aseptic bone necrosis with DQA1^*0601, and hepatomegaly with DRB1^*0405 and/or DQA1^*0401. In relation to laboratory findings, there were positive associations of hemolytic anemia with DRB1^*1402 and negative associations of leukopenia with DQA1^*0601, lymphopenia with DQA1^*0301, and proteinuria with DRB1^*0901. Interestingly, DQA1^*0101 and/or DQB1^*0501 were significantly associated with WHO classification type II rather than type IV. In patients with SLE, some HLA types related to clinical or laboratory findings. Received: March 4, 2000 / Accepted: August 15, 2000     

Time of initial appearance of renal symptoms in the course of systemic lupus erythematosus as a prognostic factor for lupus nephritis

The prognosis of lupus nephritis (LN) was studied retrospectively in two LN categories, LN manifested initially at systemic lupus erythematosus (SLE) onset (I-LN) and LN of delayed manifestation after SLE onset (D-LN), based on a chart review (C) of 154 SLE (85 LN) patients with a mean observation of 20.8 ± 9.3 years and a questionnaire study (Q) of 125 LN patients outside our hospital with mean observation of 17.6 ± 9.2 years. In both study groups, half of I-LN patients were relapse-free by Kaplan–Meier analysis after initial therapy, and the relapsed I-LN patients responded to retherapy at higher 5-year relapse-free rates than those of patients receiving initial therapies for D-LN. At last observation, a higher frequency of prolonged remission was shown in I-LN compared with D-LN patients (C: 22/31, 71% versus 14/49, 29%, P < 0.01; Q: 65/89, 73% versus 11/33, 33% P < 0.01) and also a higher frequency of irreversible renal damage in D-LN compared with I-LN patients (C: 25/49, 51% versus 2/31, 6%, P < 0.001; Q: 14/33, 42% versus 6/89, 7%, P < 0.001), although class IV pathology was common in patients (C) in both LN categories. Onset time of lupus nephritis in the course of SLE may affect renal prognosis.     

Antinucleosome antibodies in systemic lupus erythematosus patients: Relation to disease activity and lupus nephritis

Aim of the work

To evaluate the level of anti-nucleosome (anti-NCS) antibodies in systemic lupus erythematosus (SLE) patients and study their association with disease activity and lupus nephritis.

Isolation of anti-nucleosome antibodies from the plasma of lupus nephritis patients

Anti-nucleosome antibodies, which recognise conformational epitopes consisting of histone and DNA in chromatin, have been described in autoimmune diseases. In this study, an attempt was made to isolate anti-nucleosome antibodies from the anti-DNA-depleted plasma IgG of two lupus patients either with or without nephritis by nucleohistone affinity chromatography. The purified nucleohistone-binding antibodies bound to nucleohistone in a specific manner and contained enriched anti-histone antibodies. However, adsorption of the purified antibodies with histone revealed that the nephritis patient-derived antibodies contained nucleohistone-specific antibodies. Although such purified antibodies may not recognise native structures of nucleosomes, this chromatography may provide a method to isolate and determine the fine specificity of anti-nucleosome antibodies in various autoimmune diseases.     

系统性红斑狼疮血清抗核小体抗体水平及意义的探讨

目的 研究抗核小体抗体(AnuA)在系统性红斑狼疮(systemic lupus erythematosus，SLE)患者血清中的水平及其相关影响因素，探讨AnuA在SLE诊治中的作用和意义。方法 采用酶联免疫吸附法(EUSA)测定120例初诊SLE患者、55例其他风湿性疾病和30名健康对照血清中AnuA水平。同时记录各种临床表现，检测并分析其治疗前的其他自身抗体和实验室指标。结果 自身抗体在SLE及其他风湿病对照组的阳性率分别为AnuA56％和7％，抗dsDNA抗体35％和1％，抗Sm抗体24％和0。AnuA与SLE患者性别、年龄、病程无相关性，对sLE的诊断敏感性和特异性分别为55．8％、9513％，对狼疮肾炎(1upus nephritis，LN)的诊断敏感性和特异性分别为77．％、64．5%。AnuA与肝脏损害和疾病活动呈线性相关(t=3．152，2．171，P＜O．05)。AnuA分别与抗dsDNA、抗Sm联合检测对SLE诊断敏感性提高27％、40％（X^2值分别为38．930、18．161，P＜O．01)。结论AnuA在SLE血清中水平显著增高，AnuA测定是SLE诊断和治疗监测中有价值的新的实验室检测指标之一，与抗dsDNA抗体联合检测可提高诊断SLE、LN的敏感性和特异性。     

Anti-chromatin and anti-histone antibodies in Egyptian patients with systemic lupus erythematosus

There has been a renewed interest in anti-chromatin and anti-histone antibodies in the last few years. To assess the prevalence of anti-chromatin and anti-histone antibodies in patients with systematic lupus erythematosus (SLE) and to correlate serum levels of these antibodies with clinical features of the disease, the presence of anti-chromatin and anti-histone antibodies in 38 patients with SLE was investigated by an enzyme-linked immunosorbent assay (ELISA). To determine the specificity of these antibodies, 15 patients with rheumatoid arthritis, 15 patients with systemic sclerosis, and 15 normal controls were also tested. Sensitivity of anti-chromatin antibodies in SLE patients was 89.5% and specificity was 80.0%, while sensitivity of anti-histone antibodies was 92.1% and specificity was 82.2%. Significant associations were found between the levels of anti-chromatin antibodies and arthritis, malar rash, oral ulcer, pulmonary affection (P < 0.05) also, lupus nephritis (P < 0.01), and disease activity score as measured by SLE disease activity index (SLEDAI; P < 0.001). Significant association was found between anti-histone antibodies and fatigue (P < 0.05). The incidence of positive anti-chromatin and anti-histone antibodies was significantly higher than that of anti-dsDNA antibodies in early stage of the disease. We conclude that anti-chromatin and anti-histone antibodies are both sensitive and specific for SLE and could be a useful addition to the laboratory tests that can help in the diagnosis of SLE. Anti-chromatin antibodies seem to be a promising marker useful in early diagnosis and assessment of disease activity in SLE patients especially in patients who are negative for anti-dsDNA antibodies. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Anti‐nucleosome antibodies as a disease activity marker in patients with systemic lupus erythematosus

Aim: To measure the level of anti‐nucleosome antibodies in systemic lupus erythematosus (SLE) patients, to determine the sensitivity and the specificity of these antibodies in the diagnosis of the disease and to evaluate the relationship between the levels of anti‐nucleosome antibodies, anti‐dsDNA (double‐stranded DNA) and SLE disease activity. Methods: A cross‐sectional study was conducted. All patients attended either a medical specialist clinic or were admitted to the medical wards of Hospital Universiti Sains Malaysia with the diagnosis of SLE (n = 90), other connective tissue diseases (n = 45) or were normal controls (n = 90) within the period from July 2004 until September 2005. They were tested for anti‐nucleosome antibodies by enzyme‐linked immunosorbent assay and anti‐DNA antibodies by immunofluorescence. SLE disease activity was evaluated by SLE disease activity index (SLEDAI) score. Results: Out of 90 SLE patients, anti‐nucleosome antibodies were positive in 47 (52.2%) patients, whereas these antibodies were positive in three (6.7%) patients with other connective tissue diseases. Anti‐dsDNA antibodies were positive in 33 (36.7%) SLE patients, whereas these antibodies were positive in four (8.9%) patients with other connective tissue diseases. Anti‐nucleosome antibodies were positive in 40 (97.6%) patients with active SLE, whereas these antibodies were positive in seven (14.3%) patients with inactive SLE. Anti‐nucleosome antibodies had a stronger correlation than anti‐dsDNA antibodies with SLEDAI score. There was a significant association between anti‐nucleosome antibodies and disease activity. Conclusion: Anti‐nucleosome antibodies test is highly sensitive and specific for the diagnosis of SLE, especially when the anti‐dsDNA antibodies are absent. They are additional disease activity markers in the assessment of SLE disease activity.     

Assessment of lupus activity for Egyptian patients on regular hemodialysis,is there a need for prolonged immunosuppressive therapy?

Background

End stage renal disease can decrease lupus activity especially after renal replacement therapy, so assessment of activity after starting hemodialysis (HD) is essential to avoid immunosuppressive complications and prevent flares.

狼疮肾炎终末期肾病患者尸体肾移植的临床观察

目的　探讨狼疮肾炎终末期肾病 (LN ESRD)患者行尸体肾移植手术的可行性及预后和狼疮活动的情况。方法　回顾性分析我院自 1972年开展肾移植手术以来 6例LN ESRD患者在透析时、术前及术后狼疮活动性指数 (SLEDAI)以及移植的时机、移植后免疫抑制剂的使用和人 /肾存活情况。结果　 6例皆为女性患者 ,皆因LN而出现ESRD。移植前皆接受慢性透析治疗 ,其中透析距移植的时间最短为 3个月 ,最长为 9年。移植后 3例用强的松、环孢素A和霉酚酸酯三联免疫抑制治疗 ,另 3例用泼尼松、环孢素A和硫唑嘌呤治疗。 6例患者有 5例存活至今 ,平均存活 (44± 34 )个月 ,最长为 85个月 ,最短为 4个月。 1例在移植后 4个月因高血压脑出血而死亡 ,死前肾功能正常 ,且无狼疮活动。移植术后 1周内移植肾功能皆恢复正常 ,无 1例因狼疮复发而致移植肾功能减退或丧失 ,其中带肾存活最长且肾功能的保持正常者已达 77个月。在慢性透析期间及移植术后无狼疮活动 (SLEDAI<9分 )。结论　肾移植是治疗LN ESRD成功而有效的手段 ,肾移植后狼疮复发率低。