Empfehlungen zum Einsatz von Belimumab beim systemischen Lupus erythematodes

The central role of B-lymphocytes in the pathogenesis of systemic lupus erythematosus (SLE) has turned the attention particularly to more specific B-cell targeted therapies in recent years. Belimumab is a monoclonal antibody against the B-lymphocyte stimulator BlyS and was approved in 2011 as additional therapy for adult patients with SLE. Based upon the available data, treatment with belimumab is recommended in patients with clinically and serologically active SLE despite individually adjusted standard therapy. The standard therapy usually consists of antimalarial agents, an immunosuppressive drug (e.g. azathioprine) and/or steroids. Even the necessity for regular higher dosages of ≥?7.5 mg prednisolone equivalents/day could be a feasible medical indication for belimumab. Due to lacking data the use of belimumab is not recommended for the purpose of treating severe active SLE with renal or central nervous system involvement until efficacy has been shown for these indications.     

Use of belimumab throughout pregnancy to treat active systemic lupus erythematosus—A case report

Background

Pregnancy can lead to flares in systemic lupus erythematosus (SLE), and the presence of SLE in pregnancy could lead to a poor outcome for the mother and the fetus.

Objective

To describe a patient whose active SLE (including lupus nephritis) was managed with the use of belimumab throughout pregnancy.

Methods

A case report and review of relevant literature is presented.

Results

A 38-year-old Caucasian woman with SLE was seen for advice regarding planning a pregnancy and management of her active lupus (cutaneous lupus, angioedema, lupus nephritis, leukopenia, and anti-phospholipid antibody syndrome) that could only be controlled by mycophenolate, a drug contraindicated in pregnancy. Azathioprine, hydroxychloroquine, rituximab, and moderate doses of prednisone were either unable to control her disease or led to unacceptable toxicity. After detailed discussions, she was treated with belimumab, which controlled her SLE and allowed withdrawal of mycophenolate. Belimumab was continued throughout the pregnancy, leading to well-controlled SLE and uneventful course, albeit with the presence of mild Ebstein?s anomaly in the baby.

Conclusion

To our knowledge, this is the first case report of belimumab use throughout pregnancy for controlling active SLE. Data from the belimumab pregnancy registry would be useful to confirm our findings and to further assess safety of this agent for use in pregnancy.     

Lupus érythémateux cutanés réfractaires traités par bélimumab : étude descriptive monocentrique

BackgroundBelimumab is currently approved for the treatment of active systemic lupus erythematosus (SLE). The aim of our study was to evaluate the efficacy of belimumab in the treatment of cutaneous lupus erythematosus (CLE), resistant to conventional therapy.Patients and methodsSeven patients with resistant and progressive LEC and treated with belimumab were retrospectively analyzed. The efficacy and safety of belimumab were evaluated with the CLASI, RCLASI and DLQI scores, after 6 to 12 months of treatment.ResultsEighty-three percent of patients demonstrated a significant clinical improvement based on the CLASI and RCLASI activity scores, including 1 complete and 4 partial responses, without worsening of CLASI and RCLASI damage scores. Eighty percent of patients also showed an improvement of their quality of life (DLQI). Oral corticosteroids were discontinued in all patients. Tolerance was acceptable with only one serious adverse event (bacteriema).ConclusionOur study suggests the clinical efficiency of belimumab in a series of 7 patients presenting a resistant and progressive CLE.     

Low dose cyclosporine A in the treatment of resistant proliferative lupus nephritis

Objective: This study aimed to evaluate long-term efficacy of low dose cyclosporine A (CsA) in the treatment of resistant proliferative lupus nephritis.

Methods: In this retrospective study, patients with biopsy proven proliferative lupus nephritis who were unresponsive to combination therapy with steroid plus mycophenolate mofetil (MMF) or cyclophosphamide (CYC) and had been treated with CsA were included. Efficacy monitoring was based on the systemic lupus erythematosus (SLE) disease activity index, dose of prednisolone, serum complement, anti–double stranded DNA (anti-dsDNA) titration, urine analysis, proteinuria, creatinine clearance, remission of the renal disease, renal survival and involvement of other organs.

Results: This study included 27 consecutive patients (22 females, 5 males) with resistant proliferative lupus nephritis. Mean duration of follow up and treatment with CsA were 40.7?±?24.9 and 35.2?±?19.1 months, respectively. Complete and partial renal remission occurred in 66.9% and 25.7% patients, respectively. Creatinine clearance was stable, proteinuria and anti-dsDNA titer decreased, and C3 and C4 increased significantly during the treatment with CsA. Severe complications such as death, dialysis, kidney transplantation and severe infection did not occur in the studied patients during the follow-up period.

Conclusions: Low-dose CsA could induce renal remission and ameliorate the SLE disease activity in patients with resistant proliferative lupus nephritis and it would be a safe drug for treatment of these patients.     

Anti-nucleosome antibodies: A potential surrogate marker for renal affection in lupus patients with insignificant proteinuria

BackgroundLupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus (SLE). Clinical renal involvement is present in about two-thirds of lupus patients and more patients would have morphologic evidence of renal disease without clinical manifestations.Aim of the workTo investigate serum anti-nucleosome antibodies role as a biomarker for renal affection in lupus patients with insignificant proteinuria.Patients and methodsTwenty-four lupus patients with proteinuria <500 mg/d (group-A), 30 patients with established lupus nephritis (group-B) and 15 controls were included. Systemic lupus erythematosis disease activity index (SLEDAI), anti-nucleosome, anti-dsDNA antibodies and renal biopsy were assessed in all patients.ResultsSerum anti-nucleosome antibodies were significantly higher in all lupus patients than control (P < 0.001) and showed significant positive correlation with SLEDAI score. SLE patients with positive anti-dsDNA antibody had more active disease by SLEDAI and higher levels of anti-nucleosome antibodies than those with negative anti-dsDNA antibodies. In both studied groups, serum anti-nucleosome antibodies were significantly higher in patients with class II LN than the control and in class III LN than in class II LN (P < 0.001). Yet, in both groups, anti-nucleosome was not useful in differentiating active from chronic renal affection.ConclusionSerum levels of anti-nucleosome antibodies are associated with active lupus disease and correlate with the degree of renal affection. In patients with insignificant proteinuria, serum levels of anti-nucleosome antibodies were elevated and were related to the degree of renal affection. Anti-nucleosome antibodies may be used as a surrogate marker for early renal affection in lupus patients with insignificant proteinuria.     

Complement degradation product C3d in urine: marker of lupus nephritis

OBJECTIVE: To examine whether serum and urine C3d, a degradation product of C3, correlate with renal and extrarenal lupus activity. METHODS: Serum and urinary C3d levels were measured by ELISA in 15 healthy individuals and 24 patients with systemic lupus erythematosus (SLE) (8 with inactive disease, 7 with active but nonrenal disease, 9 with active lupus nephritis). Disease activity variables like serum C3, C4, and anti-dsDNA antibodies were also measured. RESULTS: The median serum C3d levels were significantly higher (p < 0.01) in patients with active (26 arbitrary units/ml; AU/ml) and inactive SLE (27 AU/ml) compared to healthy controls (11.25 AU/ml); levels were comparable in patients with active renal and extrarenal SLE. On the other hand, urine C3d was elevated only in patients with active SLE; its level was highest in patients with active lupus nephritis (0.87 AU/ml) compared to patients with active extrarenal diseases (0.31 AU/ml; p < 0.05), to patients with inactive lupus nephritis (0.06 AU/ml; p < 0.001), or to levels in healthy individuals (0.06; p < 0.001). Urine C3d showed stronger correlation with disease activity score (SLE Disease Activity Index) than serum C3, C4, anti-dsDNA antibodies, and serum C3d. CONCLUSION: Urine C3d is a good index of active lupus, particularly lupus nephritis.     

Cross-reactivity of human lupus anti-DNA antibodies with alpha-actinin and nephritogenic potential

OBJECTIVE: Cross-reactivity with kidney antigens is believed to be a critical determinant in the renal pathogenicity of anti-double-stranded DNA (anti-dsDNA) antibodies. Murine nephritogenic anti-dsDNA antibodies have been shown to cross-react with alpha-actinin, and anti-alpha-actinin antibodies have been found to be deposited in the kidneys of lupus mice with active nephritis. Furthermore, in humans with systemic lupus erythematosus (SLE), it has been found that a greater proportion of polyclonal IgG anti-dsDNA antibodies from patients with renal involvement bind to alpha-actinin than do those from patients without renal disease. We undertook this study to substantiate a direct link between cross-reactive anti-dsDNA/anti-alpha-actinin antibodies and the pathogenesis of lupus nephritis in humans. METHODS: A panel of 10 anti-dsDNA and/or anti-alpha-actinin antibodies was generated by Epstein-Barr virus transformation of lymphocytes from patients with SLE and was extensively characterized. Antibody binding was studied by enzyme-linked immunosorbent assay and Western blotting. Antibody potential for pathogenicity was assessed by measuring binding to isolated glomeruli and mesangial cells and by evaluation of histologic features of the kidney following injection in vivo. RESULTS: All anti-dsDNA antibodies isolated also bound alpha-actinin. Cross-reactive antibodies bound to mesangial cells and to isolated glomeruli ex vivo. Binding to glomeruli was not inhibited by DNase treatment, but could be abrogated by alpha-actinin. Furthermore, histopathologic abnormalities seen in mice injected intraperitoneally with a cross-reactive cell line included fusion of podocyte foot processes and subepithelial and subendothelial deposition. CONCLUSION: These studies provide strong support for the hypothesis that alpha-actinin is a major cross-reactive target for anti-dsDNA antibodies in SLE patients. Cross-reactive anti-dsDNA/anti-alpha-actinin antibodies from SLE patients are pathogenic and may contribute to the kidney lesions in lupus nephritis.     

Clinical and Laboratory Predictors of Distinct Histopathogical Features of Lupus Nephritis

The authors aimed to explore whether distinct clinical, serological, and urinalysis findings are associated with specific histological classes of lupus nephritis. Clinical and laboratory features were recorded at the time of clinical diagnosis from 297 consecutive patients with biopsy-confirmed lupus nephritis. Univariate and logistic regression analyses were performed and a risk score was developed to estimate the risk for developing different classes of lupus nephritis. Variables independently associated with class II included absence of malar rash, negative anti-dsDNA, and ≤5 urine leucocytes/high power field (hpf); with III/IV: age at nephritis diagnosis ≤32 years old, presence of musculoskeletal features, new-onset hypertension, positive anti-dsDNA, >5 urine leucocytes/hpf, creatinine >1.2 mg/dL, cellular casts >1/hpf, and absence of nephrotic range proteinuria; with V: age at nephritis diagnosis >32 years, malar rash, absence of musculoskeletal complaints or serum C3 hypocomplementemia, nephrotic range proteinuria, and ≤9 urine erythrocytes/hpf. A risk predictive score of specific histological classes was calculated for each patient. Associations between 2, 3 or more risk factors with specific histological classes were also revealed [Odds ratios (95% confidence interval) (≥2 risk factors) was 6.7 (2.8–17.4) for class II nephritis, 15.6 (5.1–47.8), and 8.2 (3.6–19.0) for classes III/IV and for class V, respectively (≥3 risk factors)]. The identification of independent factors associated with specific classes of lupus nephritis can provide guidance in selecting specific therapeutic modalities, particularly in cases in which renal biopsy is contraindicated.     

Relationship between anti-double-stranded DNA antibodies and exacerbation of renal disease in patients with systemic lupus erythematosus

OBJECTIVE: To examine the relationship between changes in anti-double-stranded DNA (anti-dsDNA) antibody levels and the risk of renal flare in patients with systemic lupus erythematosus (SLE), using data from 2 randomized, controlled trials. METHODS: Analyses were based on 487 patients with SLE and a history of lupus nephritis who had an anti-dsDNA antibody titer >/=15 IU/ml at baseline, as measured by Farr assay. Results are presented for the combined population of patients, the placebo arms, and the drug treatment arms in which a dsDNA-based bioconjugate (abetimus sodium; LJP 394) was used. RESULTS: Changes in anti-dsDNA antibody levels were inversely correlated with changes in the C3 level (P < 0.0001 in both trials). Cox proportional hazards regression models showed that changes in anti-dsDNA antibody levels correlated with the risk of renal flare. The models predicted that a point estimate of a 50% reduction in anti-dsDNA antibody levels is associated with a 52% reduction (95% confidence interval [95% CI] 26-68%, nominal P = 0.0007) and a 53% reduction (95% CI 33-69%, nominal P < 0.0001) in the risk of renal flare in the 2 trials, respectively. In the 2 trials, the incidence of renal flare was lower in patients with sustained reductions in anti-dsDNA antibodies (3.0% and 4.1%, respectively) than in patients with stable or increasing antibody levels (21.3% and 20.3%, respectively). CONCLUSION: Changes in anti-dsDNA antibody levels were directly correlated with the risk of renal flare and inversely correlated with changes in the C3 level. Reducing anti-dsDNA antibody levels may represent a therapeutic objective in SLE patients with lupus nephritis, because it is associated with a reduced risk of renal flare.     

The use of belimumab in three cases of refractory lupus nephritis

In recent trials for the treatment of systemic lupus erythematosus (SLE), belimumab (BLM), in addition to standard immunosuppression, has been shown to improve renal and nonrenal outcomes. We report our experience using BLM in three cases of refractory lupus nephritis (LN), where renal remission was not achieved using cyclophosphamide, mycophenolate mofetil and other immunosuppressive medications. In two of the three cases, BLM therapy led to a partial remission of LN, improvement in serological markers of SLE and disease activity, which permitted a reduction in prednisolone dosing. Treatment with efficacious therapies early in the course of LN is a desirable therapeutic strategy, to achieve early remission of proteinuria and curtail the development of irreversible chronic renal damage. Further studies are needed to provide information on the effectiveness of BLM for maintenance of remission, prevention of flares and monitoring for long-term complications of B-cell modulation.     

Systemic lupus erythematosus within the first two decades of life

Forty-nine patients with systemic lupus erythematosus (SLE) during childhood and adolescence presenting over a period of 17 years were followed during treatment with prednisone and azathioprine. The average period of follow-up was 5.7 years. Detailed analyses of clinical parameters of renal function and sequential changes in glomerular abnormalities by percutaneous renal biopsy are reported. Therapy was directed towards normalizing the results of urinalysis and renal function, eliminating proteinuria and maintaining normal serology (normal serum complement and negative antiDNA titers). The 10 year survival of the entire group was 86 per cent. A survival of 73 per cent and 87 per cent over this interval in patients with diffuse and focal proliferative lupus nephritis, respectively, was achieved. The major cause of mortality in this series was infection. It appears that intensive observation and monitoring of serologic parameters in SLE, along with aggressive steroid and immunosuppressive therapy, lead to a prognosis in SLE more favorable than previously reported.     

Clinical significance of anti-dsDNA antibody isotypes: IgG/IgM ratio of anti-dsDNA antibodies as a prognostic marker for lupus nephritis

The objective of this paper is to investigate the association between patterns of anti-dsDNA antibody isotypes and specific clinical manifestations (categorized in renal, musculoskeletal, cutaneous, hematological, pulmonary, neurological and cardiac). Sera of 202 systemic lupus erythematosus (SLE) patients, 33 patients suffering from other autoimmune diseases and 115 healthy blood donors were analysed for anti-dsDNA antibodies by IgG-, IgA- and IgM-specific ELISA, Farr-assay and CLIF. A subset of 24 SLE patients was investigated in a longitudinal study over a period of one to six years. Disease activity of 105 SLE patients was measured according to the ECLAM score. In the cohort of SLE patients 63% were positive for the IgG class, 40% for the IgA and 57% for the IgM class specific anti-dsDNA ELISA. Sensitivity (79%) and specificity (99%) for the diagnosis of SLE appeared to be highest for the ELISA measuring all isotypes of anti-dsDNA antibodies. The concentrations of anti-dsDNA isotypes showed a strong correlation with disease activity. Analysing the relationship between IgG, IgA and IgM anti-dsDNA antibody isotypes and clinical manifestation, we found a significant association of the IgM isotype with cutaneous involvement and of the IgG isotype with lupus nephritis. The IgG/IgM ratio of anti-dsDNA antibodies represented a significant parameter to distinguish patients with lupus nephritis from those without renal involvement. In the longitudinal study, a continuous ratio under 0.8 was associated with absence of renal involvement throughout the investigated period. In conclusion, the evaluation of anti-dsDNA isotypes provides a diagnostic tool to define subsets within SLE patients with different clinical manifestations. In particular, the IgG/IgM ratio of anti-dsDNA antibodies could be used as a prognostic marker for lupus nephritis during the course of the disease.     

Anti-dsDNA,anti-Sm antibodies,and the lupus anticoagulant: significant factors associated with lupus nephritis

BACKGROUND: Lupus nephritis (LN) is a common manifestation in patients with systemic lupus erythematosus (SLE). Autoantibodies and ethnicity have been associated with LN, but the results are controversial. OBJECTIVE: To study the immunological and demographic factors associated with the development of LN. PATIENTS AND METHODS: A retrospective case-control study of 127 patients with biopsy-proven LN, and 206 randomly selected patients with SLE without nephritis as controls was designed. All patients had attended our lupus unit during the past 12 years. Standard methods were used for laboratory testing. RESULTS: Patients with LN were significantly younger than the controls at the time of SLE diagnosis (mean (SD) 25.6 (8.8) years v 33.7 (12.5) years; p<0.0001). The proportion of patients of black ethnic origin was significantly higher in the group with nephritis (p=0.02). There were no differences in sex distribution or duration of follow up. A higher proportion of anti-dsDNA, anti-RNP, anti-Sm, and lupus anticoagulant (LA) was seen in the group with nephritis (p=0.002; p=0.005; p=0.0001; p=0.01, respectively). In univariate, but not in multivariate, analysis male sex and absence of anti-dsDNA were associated with earlier onset of renal disease (p=0.03; p=0.008). In multivariate analysis the only factors associated with nephritis were younger age at diagnosis of SLE, black race, presence of anti-dsDNA, anti-Sm, and LA. No demographic or immunological associations were seen with WHO histological classes. CONCLUSIONS: Young, black patients with anti-dsDNA, anti-Sm antibodies, and positive LA, appear to have a higher risk of renal involvement. These patients should be carefully monitored for the development of LN.     

Belimumab: targeted therapy for lupus

Systemic lupus erythematosus (SLE), a complex autoimmune disease with multisystem involvement, is characterised by recurring flares and remissions throughout the course of illness. The agents currently being used for management include corticosteroids, antimalarials and various immunosuppressants. Belimumab, a B lymphocyte stimulator (BLyS) inhibitor has been recently approved for the treatment of SLE. This review aims to discuss the role of belimumab in the treatment of SLE and the trials leading to its FDA approval. Belimumab demonstrated high degree of activity in patients with autoantibody‐positive active SLE disease on a stable treatment regimen. There was a significantly greater response compared to placebo as assessed with the SLE Responder Index (SRI) in two randomized, double‐blind, phase III trials (BLISS‐52 and BLISS‐76). The treatment was well tolerated. Additional studies are required to evaluate belimumab in special populations and assess its long‐term safety. This therapy could change the focus of management from symptomatic treatment to targeting an important step in the disease pathogenesis. It could enable development of treatment which could halt long‐term progression, minimize target organ damage and thus provide a better quality of life for these patients.     

Anti-nucleosome antibodies may predict lupus nephritis and severity of disease in systemic lupus erythematosus

Background/ObjectiveDetection of anti-nucleosome antibodies in patients with systemic lupus erythematosus (SLE) has been well established and it is claimed that their presence is associated with disease activity. The objective of this study is to determine the diagnostic value of anti-nucleosome antibodies in the assessment of lupus nephritis and clinically active SLE.MethodsThe anti-nucleosome antibodies were evaluated in the serum of 200 Tunisian SLE patients at disease onset by a sensitive immunodot assay. Serum samples from each patient were also tested for ANA and anti-ds DNA antibody by IIF on Hep 2 cells and Crithidia luciliae respectively. During the follow-up, the patients were regularly monitored for clinical parameters. Global SLE activity was measured by the European Consensus Lupus Activity Measurement (ECLAM).ResultsThe prevalence of anti-nucleosome and anti-dsDNA antibodies was 69% and 63.5% respectively. Anti-nucleosome antibodies were found to be 30.1% positive in SLE patients lacking anti-dsDNA antibody. 79.5% patients had active SLE at the first clinical examination. Anti-nucleosome antibodies were more sensitive than anti-dsDNA antibodies to detect active SLE (78% vs. 71.7%, P =0.19). 52.5% of SLE patients had renal involvement. Among these patients, the rate of anti-nucleosome positivity and anti-dsDNA were 77.1% and 67.6% respectively. The positivity of anti-nucleosome antibodies was significantly higher in patients with renal disease than the subjects without renal disease (P = 0.009). Anti-nucleosome and anti-ds DNA antibodies were significantly correlated with disease activity (P < 0.001 and P < 0.001 respectively).ConclusionAnti-nucleosome antibody reactivity may be a useful marker in the diagnosis and assessment of active SLE.     

A regulatory role for CD72 expression on B cells in systemic lupus erythematosus

BackgroundB regulatory cells and their regulatory products/markers, such us semaphorin 3A (sema3A) and its receptor NP-1, FcγIIB, IL-10, and others, act at the very base of self-tolerance, maintenance, and prevention of autoimmune disease development.ObjectivesThe aim of the present study was to assess the involvement of CD72, a regulatory receptor on B cells, in systemic lupus erythematosus (SLE). In addition, the potential of soluble sema3A in enhancing the expression of CD72 on B cells of SLE patients was investigated.ResultsCD72 expression on activated B cells of SLE patients was significantly lower than that of normal controls. This lower expression of CD72 in SLE patients correlated inversely with SLE disease activity and was associated with lupus nephritis, the presence of anti-dsDNA antibodies, and low levels of complement. Co-culture of purified B cells from healthy controls with condition-media containing recombinant sema3A resulted in significant enhancement of CD72. Similar enhancement of CD72 on activated B cells from SLE patients, though significant, was still lower than in normal individuals.ConclusionsThe lower expression of CD72 on activated B cells from SLE patients correlates with SLE disease activity, lupus nephritis, the presence of anti-dsDNA antibodies, and low levels of complement. The improvement of CD72 expression following the addition of soluble semaphorin 3A suggests that CD72 may be useful as a biomarker to be followed during the treatment of SLE.     

Neutrophil to lymphocyte and platelet to lymphocyte ratios in systemic lupus erythematosus: Relation with disease activity and lupus nephritis

ObjectivesTo investigate the role of neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as activity markers in systemic lupus erythematosus (SLE) without nephritis and lupus nephritis (LN) patients.Patients and methodsThis study included 60 SLE patients with LN, 60 SLE patients without renal involvement and 30 healthy controls. We analyzed correlations between NLR and PLR and both disease activity and renal affection.ResultsThe NLR of SLE patients was much higher than those of the controls. Both ratios showed significantly increased values in SLE patients with active disease. NLR and PLR were positively correlated with SLEDAI, ESR, and CRP and negatively correlated with C4. SLE patients with LN had higher levels of NLR than those without nephritis. NLR showed positive correlations with BUN, serum urea, serum creatinine and 24 h urinary protein. We found NLR to be related to anti-ds-DNA level and renal biopsy classes. While PLR was related only to anti ds-DNA. The best NLR to predict SLE active disease was 2.2 and the best PLR cut-off value was 132.9.ConclusionNLR and PLR are useful inflammatory markers to evaluate disease activity in SLE patients. Also, NLR could reflect renal involvement in SLE patients and is associated with the different classes of its histological staging.     

血清C1q抗体水平与系统性红斑狼疮活动性和狼疮肾炎的关系

目的分析探讨血清C1q抗体水平与系统性红斑狼疮（SLE）活动性以及狼疮肾炎之间的关系。方法采用ELISA方法检测92例SLE患者C1q抗体水平。并与其他SLE活动性指标进行相关分析。结果SLE患者C1q抗体阳性率为67.4%。活动性狼疮组的C1q抗体阳性率及C1q抗体水平显著高于非活动性狼疮组（P〈0.001）。活动性狼疮肾炎组C1q抗体阳性率（P〈0.05）和C1q抗体水平（P〈0.01）显著高于非活动性狼疮肾炎组。联合抗dsDNA抗体检测,没有1例活动性狼疮肾炎患者的C1q抗体和抗dsDNA抗体同时阴性。结论血清C1q抗体与狼疮活动以及活动性狼疮肾炎关系密切,C1q抗体的检测有助于活动性狼疮的诊断,联合抗dsDNA抗体的检测是活动性狼疮肾炎的特异性检测指标。     

狼疮肾炎危险因素分析

目的探讨狼疮肾炎(LN)病变的危险因素。方法对79例LN患者进行回顾性分析,并与同期住院的91例无肾炎病变的SLE患者作对照。所有实验室检查均采用标准方法。结果LN患者占同期住院患者的40.3%。与无肾炎病变的SLE患者作对照,其发病年龄明显小于对照组(P<0.001),两组性别和病程方面差异无显著性(P>0.05)。实验室指标对比显示,抗dsDNA抗体、抗Sm抗体、抗心磷脂抗体(aCL)和抗中性粒细胞胞质抗体(ANCA)在LN组有较高的阳性率,与对照组相比差异有显著性(P<0.05)。结论发病年龄小,存在抗dsDNA抗体、抗Sm抗体、aCL和ANCA阳性是SLE易并发肾炎的危险因素。     

Urinary lipocalin-2 is associated with renal disease activity in human lupus nephritis

OBJECTIVE: Pathogenic monoclonal anti-double-stranded DNA (anti-dsDNA) antibodies up-regulate the expression of lipocalin-2 in glomerular mesangial cells. This study was undertaken to investigate whether polyclonal anti-dsDNA antibodies promote the local secretion of lipocalin-2 in the kidneys of patients with systemic lupus erythematosus (SLE), and whether urinary lipocalin-2 represents a marker of kidney involvement in SLE. METHODS: Hispanic, African American, and white patients with SLE and normal healthy control subjects from affiliated hospitals of the Albert Einstein College of Medicine were recruited for this cross-sectional study. Patients were classified based on the presence of active renal disease according to the SLE Disease Activity Index (SLEDAI). Correlations of clinical and laboratory data with urinary and serum levels of lipocalin-2 were assessed. RESULTS: Among SLE patients, urinary lipocalin-2 levels were significantly higher in those with lupus nephritis (LN) (median 17.1 ng/mg creatinine, interquartile range [IQR] 10.3-45.4; n = 32) than in those without LN (median 11.2 ng/mg creatinine, IQR 3.1-20.3; n = 38) (P = 0.023). Compared with the values in normal controls (median 4 ng/ml, IQR 0-11.1; n = 14), urinary levels of lipocalin-2 in SLE patients were significantly higher (non-normalized median 19.3 ng/ml, IQR 8-34.2) (P = 0.004). The presence of lipocalin-2 in the urine of patients with LN correlated significantly with the renal SLEDAI score (r = 0.452, P = 0.009), but not with extrarenal disease activity. CONCLUSION: The high prevalence of LN in SLE patients and the prognostic significance of kidney disease support the need for identifying early biomarkers to assess the risk of nephritis development and for following up patients with established disease. These findings indicate that urinary lipocalin-2 is a potential marker of the presence and severity of renal involvement in adult patients with SLE.