Anti-C1q antibodies are associated with systemic lupus erythematosus disease activity and lupus nephritis in northeast of China

This study aimed to investigate the associations of anti-C1q antibodies with systemic lupus erythematosus (SLE) disease activity and lupus nephritis (LN) in northeast of China. Ninety patients with SLE, 37 patients with other autoimmune diseases, and 40 healthy donors in northeast of China were enrolled. Serum anti-C1q antibodies were measured by ELISA with 20 RU/ml as the threshold of positive results. The prevalence and levels of anti-C1q antibodies in SLE group (50%, 20.54 ± 34.67 RU/ml) were significantly higher than those in autoimmune disease and healthy control groups (P < 0.05), yet no significant difference between LN patients and non-LN lupus patients (57.14% vs 41.46%, P > 0.05; 25.92 ± 39.94 vs 13.07 ± 27.39 RU/ml, P > 0.05). Anti-C1q antibody levels were positively correlated with levels of Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, anti-dsDNA, and anti-cardiolipin and negatively correlated with serum C3 and C4 (P < 0.05). The prevalence of anti-Sm and anti-nucleosome increased in anti-C1q-positive lupus patients (P < 0.05). Compared with anti-C1q-negative lupus patients, patients with 20–40 RU/ml anti-C1q antibodies had comparable disease activity (P > 0.05); patients with 40–80 RU/ml anti-C1q antibodies had significantly lower levels of serum complement (P < 0.05); patients with above 80 RU/ml anti-C1q antibodies had much more severe hypocomplementemia, increased SLEDAI scores, and higher incidence of hematuria and proteinuria (P < 0.05). Furthermore, the specificity and positive predictive value of 80 RU/ml anti-C1q antibodies for LN was 97.56% and 87.50%, respectively. In conclusion, anti-C1q antibodies are associated with SLE and LN disease activity, and the contribution hinges on the titers. Moreover, high-level anti-C1q antibodies are valuable for diagnosing LN.     

Association of serum uric acid with lupus nephritis in systemic lupus erythematosus

The aim of the present study is to assess the association of elevated serum uric acid (UA) with lupus nephritis (LN) in systemic lupus erythematosus (SLE) patients. A total of 130 SLE patients were recruited, of whom 73 patients developed LN. Blood samples were obtained for determination of uric acid, complement 3 (C3), C-reactive protein (CRP) and some autoantibodies including anti-double-stranded DNA, -Smith, -SSA, -SSB, -U1RNP, SCL-70, and -Jo-1 antibodies. Correlations of UA with LN were assessed. UA was an independent risk factor for LN [odds ratio (95% CI): 1.01 (1.005–1.014); P = 0.0000]. The best cut-off value for UA using the ROC curve was 330 μmol/L (sensitivity 78.1% and specificity 75.4%) and the area under the ROC curve was 0.803 ± 0.039 (95% CI: 0.727–0.878, P = 0.000). Spearman’s correlation coefficient analysis showed negative association of UA with C3 in SLE patients with LN (r = −0.356, P = 0.002), but no association in those without LN. No correlations were found between UA and age, SLEDAI, CRP, IgG, IgM or IgA. Furthermore, analysis of covariance demonstrated that anti-Sm (β = −0.218, P = 0.004) and -U1RNP (β = 0.177, P = 0.008) autoantibodies were independent determinants of serum UA. The UA level is independently associated with the development of LN in SLE patients.     

Male gender results in more severe lupus nephritis

Gender may produce different characteristics in the manifestation of systemic lupus erythematosus (SLE). The present study investigated the influence of gender on clinical, laboratory, autoantibodies and histopathological classes of lupus nephritis (LN). As much as 81 patients diagnosed with SLE (ACR criteria) and active nephritis, who underwent renal biopsy between 1999 and 2004, and who had frozen serum samples and clinical data available from the time of biopsy, were selected for this study. The presence of anti-P and antichromatin antibodies was measured using ELISA, and anti-dsDNA was measured using indirect immunofluorescence. All of the renal biopsies were reviewed in a blinded manner by the same expert renal pathologist. The charts were extensively reviewed for demographic and renal features obtained at the time of the biopsy. Of the 81 patients (13.6%), 11 were male SLE patients. Both male and female lupus patients were of similar age and race, and had similar durations of lupus and renal disease. The female patients had more cutaneous (95.7 vs. 45.5%, P = 0.0001) and haematological (52.9 vs. 18.2%, P = 0.04) involvements than the male SLE patients. In addition, the articular data, central nervous system analyses, serositis findings and SLEDAI scores were similar in both experimental groups. Positivity for anti-dsDNA, anti-ribosomal P and antichromatin did not differ between the two groups, and both groups showed similarly low C3 or C4 serum levels. Our analysis indicated that no histopathological class of LN was predominant in both males and females. Interestingly, the serum creatinine levels were higher in the male SLE patients compared to the female SLE group (3.16 ± 2.49 vs. 1.99 ± 1.54 mg/dL, P = 0.03), with an increased frequency of high creatinine (81.8 vs. 47.1%, P = 0.04) as well as renal activity index (7.6 ± 3.5 vs. 4.8 ± 3.5, P = 0.02). In addition, whilst the mean levels of proteinuria, cylindruria and serum albumin were markedly altered, they were comparable between both lupus men and women. Moreover, the frequencies of dialysis, renal transplantation and death were similar between the two groups. These data suggest that male patients had a more severe LN compared to women diagnosed with this renal abnormality.     

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     

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.     

The efficacy of low-dose mycophenolate mofetil for treatment of lupus nephritis in Taiwanese patients with systemic lupus erythematosus

Mycophenolate mofetil (MMF) has recently been introduced as an immunosuppressive agent for the treatment of glomerulonephritis with systemic lupus erythematosus (SLE) and the data have been encouraging. However, response to MMF treatment appears to differ ethnically. Therefore, we determined efficacy and safety of low-dose MMF for Taiwanese patients with lupus nephritis. We studied 36 lupus nephritis patients who were treated with MMF. The dose started at 0.5 g/day and we collected the data from patients who received up to 1 g/day MMF. Outcome measures were 24 h for proteinuria, serum creatinine, C3/C4 levels, and anti-dsDNA titers collected at the baseline and at 3-month treatment intervals. Daily urinary protein significantly decreased from 6.15 ± 4.28 g to 2.69 ± 2.36 g at the last visit (P < 0.01) in spite of the significant absence of changes in serum creatinine levels. The response rate was 65.7% including five (14.3%) cases of complete remission and 18 (51.4%) cases of partial remission. The concomitant oral prednisolone dose decreased significantly from 20.07 ± 11.78 mg/day to 13.93 ± 6.79 mg/day at 6 months (P < 0.01). The level of C3 increased significantly from 59.46 ± 32.73 to 71.99 ± 25.81 (P < 0.01) and the anti-dsDNA antibody titer decreased from 161.71 ± 221.42 to 46.57 ± 117.47 (P < 0.01). No severe adverse effects were observed in the study. Low-dose MMF (0.5 to 1 g/day) combined with glucocorticoids appears to be a safe and effective therapy for lupus nephritis in Taiwanese patients. Our results suggest that lupus nephritis in Oriental patients might respond to lower doses of MMF than Caucasians.     

Anti-dsDNA antibodies in Brazilian patients of mainly African descent with systemic lupus erythematosus: lack of association with lupus nephritis

Renal disease is associated with morbidity and mortality in systemic lupus erythematosus (SLE) and anti-dsDNA antibodies with SLE immunopathogenesis. We investigated the dsDNA antibody profile of 84 Brazilian SLE patients, 27 with lupus nephritis. Thirty-six (39.1%) patients had dsDNA IgG antibodies shown in enzyme-linked immunosorbent assay (454.7 ± 281.1 WHO units/mL), nine presenting renal disease. The following profile of dsDNA antibodies was demonstrated in Crithidia luciliae test: IgA (seven out of 36; 19.4%), IgG (22 out of 36, 66.1%); IgM (nine out of 36, 25.0%), and IgE (four out of 36, 11.1%). Two or three isotypes of dsDNA antibodies were observed in nine (25.0%) patients, while 11 (30.5%) were seronegative in the C. luciliae test. Patients with dsDNA antibodies had lower serum C3 and C4 when compared with SLE individuals without these immunoglobulins (P < 0.01 and P < 0.001, respectively). There was no association between any dsDNA antibody isotype and lupus kidney disease nor was anti-dsDNA IgM antibody associated with absence of nephritis.     

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.     

Factores predictores del desarrollo de nefritis lúpica después del diagnóstico de lupus eritematoso sistémico

ObjectiveTo determine predictive factors for the development of lupus nephritis (LN) at the time of diagnosis of systemic lupus erythematosus (SLE).MethodsA case-control study was carried out in a single centre, 595 patients participated diagnosed with SLE without LN by clinical or laboratory parameters at diagnosis. They were followed for a mean of 6.8 (± 4.5) years, two groups were formed from the data from their records: with NL (cases) and without NL (controls) at the end of the follow-up. Sociodemographic, clinical, serological, immunological variables and albumin/globulin ratio (AGR), calculated as albumin / total protein ? albumin at diagnosis, were compared between both groups. A univariate and multivariate analysis was carried out.Results124 (20.8%) patients had LN during follow-up and 471 (79.2%) did not develop LN. Univariate analysis: variables significantly associated with the development of LN: smoking, oral ulcers, serositis, more than four classification criteria, abrupt onset of SLE, higher SLEDAI score, low AGR, low C3 levels, high anti-titres double stranded DNA (anti-dc DNA), anti-nucleosomes and positivity of immunofluorescence in skin. Multivariate analysis: predictors of developing LN: elevated serum levels of anti-dc DNA (odds ratio [OR]: 15.82; confidence interval [CI]: 1.08-1.22, P < .0001), decrease in C3 fraction (OR: 36.50; CI: 13.52-81.91, P < .0001) and RAG < 1 (OR: 47.58; CI: 11.85-79.17, P < .0001).ConclusionAn AGR below one was the greatest predictor of the appearance of LN, together with low levels of C3 and high levels of anti-dc DNA antibodies; these may contribute to identifying patients at higher risk of presenting LN.     

Serum level of galectin-9 in systemic lupus erythematosus patients with lupus nephritis: Relation to clinical characteristics and disease activity

Aim of the workTo assess galectin-9 (Gal-9) level in the serum of systemic lupus erythematosus (SLE) patients with and without renal involvement and clarify its relation with disease activity.Patients and methods50 SLE patients; 25 with lupus nephritis (LN) and 25 without as well as 25 controls were studied. Systemic Lupus International Collaborating Clinics (SLICC) renal activity score and SLE disease activity index 2000 (SLEDAI-2 K) were determined. Serum Gal-9 was measured in all participants.ResultsGal-9 level was significantly elevated in SLE patients with (16.7; 11.6–33.7 ng/ml) and without (15.9; 11.8–25 ng/ml) compared to controls (3.9; 2.8–5.4 ng/ml) (p < 0.001) but was comparable between the patients groups (p = 0.83). In LN patients, serum Gal-9 and SLICC renal activity score significantly correlated (r = 0.48, p = 0.016). Serum Gal-9 significantly correlated with SLEDAI-2 K in patients with (r = 0.71, p < 0.001) and without (r = 0.95, p < 0.001) LN, with anti-double stranded deoxyribonucleic acid (anti-ds-DNA) titers (with r = 0.57, p < 0.001 and without r = 0.79, p < 0.001) and inversely with C3 (with r = -0.44, p = 0.027 and without r = -0.63, p < 0.001) and C4 (with r = -0.47, p = 0.018 and without r = -0.43, p = 0.03). Gal-9 had an area under the curve (AUC) of 0.96 to distinguish SLE cases from control. However, AUC between LN group and non-nephritic SLE was 0.48. On regression, SLEDAI-2 K was the only significant factor associated with serum Gal-9 (p < 0.001).ConclusionIn SLE patients, significantly raised Gal-9 levels and relation with disease activity were detected indicating its clinical relevance as biomarker of disease activity and its potential value in the disease diagnosis. Its value in discriminating LN from non-nephritic SLE is limited.     

Evaluation of visfatin in patients with systemic lupus erythematosus: Correlation with disease activity and lupus nephritis

IntroductionRenal involvement affects about 50% of SLE patients accounting for significant morbidity and mortality in these patients. The adipokine “visfatin” acting as a growth factor for B-lymphocyte-precursors, exerts several proinflammatory functions. It was demonstrated as a marker of endothelial dysfunction (ED) in chronic kidney disease (CKD) thus could be a factor linking inflammation in SLE and kidney disease.Aim of the workTo assess serum visfatin level in SLE patients and its correlation to disease activity and lupus nephritis (LN) in these patients.Patients and methodsSerum level of visfatin using enzyme-linked immunosorbent assay (ELISA), chemical and immunological markers of SLE and LN were measured in 40 SLE patients and 40 age and sex matched healthy controls. Disease activity and renal involvement were assessed using SLE Disease Activity Index (SLEDAI) and Renal SLEDAI respectively further dividing patients into active versus inactive and LN versus non-LN respectively. Renal biopsies were taken from LN subgroup and were classified according to the modified WHO classification.ResultsA significantly higher serum visfatin level was found on comparing SLE patients (mean 109 ± 180 ng/ml, median18) with controls (mean 9.4 ± 11 ng/ml, median2.5) with statistically highly significant difference (z = 5.2, P < 0.001). Also there was a statistically significant difference as regards serum visfatin level between active SLE patients (mean 173 ± 111 ng/ml, median 14) and inactive patients (mean 139 ± 88 ng/ml, median 5) (z = 2.1, P < 0.05) as well as between patients with LN (mean 226 ± 180 ng/ml, median18) and patients with no LN (mean 101 ± 140 ng/ml, median 8(2-229)) (z = 2.1, P < 0.05). Visfatin had a highly significant positive correlation with disease duration (r = 0.48, P < 0.001), SLEDAI (r = 0.62, P < 0.001) as well as ESR, CRP and, renal score (r = 0.45, 0.35, and 0.65, respectively) while inverse correlation with estimated GFR (r = ?0.614) and C3 and C4 titre (r = ?0.26, r = ?0.35, respectively) was recorded. Visfatin showed high sensitivity in detecting active SLE and LN 83% and 85%, respectively.ConclusionSerum visfatin is strongly associated with LN in SLE patients and is a promising biomarker for prediction of renal involvement in these patients. It reflects SLE activity specially LN activity namely renal score and GFR decline. Further prospective studies are required to confirm visfatin as a destructive mediator of predictive and prognostic value in active lupus nephritis.     

Outcome of lupus renal disease in the past two decades: a report from China

Objective: To evaluate the differences in the renal survival of lupus nephritis (LN) diagnosed either during 1985–1994 or 1995–2004 and to analyse the possible causes. Methods: Fifty‐two patients with biopsy‐confirmed LN were followed up between 1985 and 1994 and 130 patients were followed up between 1995 and 2004. Renal survival was studied with Kaplan‐Meier analysis and the log rank test. Status at diagnosis and treatment schedules were also analysed. Results: Renal survival was significantly better in the patients who were diagnosed between 1995 and 2004 (P = 0.0233). The mean time from initiation until first diagnosis of SLE, from the initiation of SLE until referral to our centre, and from first detection of proteinuria until kidney biopsy was significantly shorter in the later decade (P < 0.05). In the decade from 1995 to 2004 there was significantly lower rates of early renal dysfunction and fewer histological signs of chronicity at the time of diagnosis of LN than in the decade from 1985 to 1994. In treatment schedules, more patients received intravenous cyclophosphamide (CTX) in a bolus in the later decade group (P = 0.014). Besides CTX, some new immunosuppressive agents such as cyclosporin A or mycophenolate mofetil were received by more patients in the decade from 1995 to 2004. Conclusions: The outcomes for patients with LN was significantly better between 1995 and 2004 than between 1985 and 1994. The result is maybe attributable to earlier diagnosis, earlier treatment, intravenous bolus CTX and more immunosuppressive agents from which to select.     

Chest imaging manifestations in lupus nephritis

The purpose of this study was to analyze the association between renal histopathological features and chest computed tomography (CT) findings in lupus nephritis (LN) patients. We retrospectively reviewed the medical records and chest thin-section CT findings of 152 patients with an established diagnosis of LN based on renal biopsy and 93 systemic lupus erythematosus (SLE) patients without LN between April 2009 and March 2012. The 64-detector row CT images were retrospectively evaluated by an experienced thoracic radiologist without knowledge of the patients’ clinical information except that all patients had SLE. Lupus nephritis patients have a significantly higher incidence of lung/plural disease than those without LN (61.8 versus 44.0 %, p?<?0.05). The patients in LN group were more prone to ground glass opacity, interlobular septal thickening, reticular opacities, pleural effusions, and consolidation on CT images than in non-LN group (p?<?0.05). Class I, class III, and class IV lupus nephritis were associated with traction bronchiectasis, ground glass opacity, and pleural effusions, respectively (p?<?0.05). The presence of cord on chest CT scans was significantly associated with renal interstitial lesion and interstitial inflammation/fibrosis (p?<?0.05). Ground glass opacity and reticular opacities on chest CT scans were also related to renal hyaline thrombi (p?<?0.05). There was a significant association between pleural effusions and cellular/fibrous crescents, interstitial lesion, or interstitial inflammation/fibrosis (p?<?0.05). It was shown that hyaline thrombi in renal biopsy was an independent risk factor of the presence of ground glass opacity on CTs with logistic regression analysis (Wald?=?4.124, p?=?0.042). LN patients were more likely to suffer from lung/pleural disease. The patients with hyaline thrombi in renal biopsy were more prone to have ground glass opacity on CTs.     

Diffusion-weighted MR imaging of kidneys in patients with systemic lupus erythematosus: initial experience

To evaluate kidney perfusion and diffusion in patients with systemic lupus erythematosus (SLE) and define any correlation between laboratory features of renal involvement and apparent diffusion coefficients (ADCs). We studied 35 patients with SLE and 30 healthy volunteers. Ten of the patients were diagnosed as having lupus nephritis. Transverse diffusion-weighted multisection echo-planar magnetic resonance imaging was created with the following diffusion gradient b values: 0, 111, 222, 333, 444, 556, 667, 778, 889, and 1,000 s/mm². Statistical analyses to compare ADCs of kidneys between patients in the study and control groups were done with the independent sample t test. The Pearson correlation analysis was used to evaluate the relation between the renal function variables and the ADCs. There was statistically significant difference between the ADC_low values and the urine protein levels (P < 0.05) in the patients with SLE. Also, there was a significant correlation between the duration of nephritis and urine protein levels in the patients with SLE (P < 0.01). There was no statistically significant differences regarding ADCs, serum creatinine levels, and GFRs among patients with SLE and controls. Our patients had mild SLE and this might be the reason that no statistically significant differences were found between ADCs, and laboratory features of renal involvement among patients with SLE and controls. Larger series and more diffusion experience may be valuable for future studies.     

High-titer antichromatin antibody is associated with proliferative class IV of lupus nephritis

The antichromatin antibody (aCT) has been described as a useful marker for lupus nephropathy. The relevance of its nephritogenic potential may be appropriately evaluated in the context of renal histopathology. Therefore, the present study investigated the relationship of aCT with a particular histopathologic class of lupus nephritis (LN). Seventy-eight consecutive patients with systemic lupus erythematosus (ACR criteria) and active nephritis who underwent renal biopsy from 1999 to 2004 and with available frozen serum sample obtained at the time of biopsy were selected. aCT was measured by ELISA, and anti-dsDNA was measured by indirect immunofluorescence (IIF) and by ELISA. All renal biopsies were revised in a blinded manner by the same expert renal pathologist. Charts were extensively reviewed for demographic and renal features obtained at the time of biopsy. The prevalence of aCT (≥20 U) was 59% with a mean titer of 74.3 ± 38.7U. Both aCT-positive and aCT-negative groups of patients had similar age, gender distribution, duration of lupus, and duration of renal disease. Anti-dsDNA was detected by IIF in 29.5% and by ELISA in 42.3% of the patients. Concomitant presence of both antibodies was observed in 63% (29/46) [anti-dsDNA by ELISA] and 45.6% (21/46) [anti-dsDNA by IIF] of the patients. Lower serum levels of C3 (73% vs. 40%, P  = 0.0058) and C4 (82% vs. 46.7%, P  = 0.0021) were more commonly observed in aCT ≥ 20 U patients compared to the aCT-negative group. It is important to note that the use of a higher cut-off value (≥40 U) for aCT test revealed a predominance of class IV LN (58% vs. 33%, P  = 0.039) in aCT ≥ 40 U compared to aCT < 40 U group. The mean levels of proteinuria, serum albumin, and creatinine were markedly altered but were comparable in both groups (P ≥ 0.05). One fourth (26.3%) of the 19 patients with class IV LN and aCT ≥ 40 U had no detectable anti-dsDNA (ELISA). These data suggest that high-titer aCT seems to be a valuable biomarker for proliferative class IV of LN.     

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.     

Treatment response and progression to end stage renal disease in adolescents and young adults with lupus nephritis: A follow up study in an Egyptian cohort

BackgroundLupus nephritis (LN) badly affects the outcome in adolescents and young adults with systemic lupus erythematosus (SLE). Many have renal disease at onset and the significance of remission and relapse in adolescents and young adults is poorly evaluated.Aim of workTo outline the clinical and laboratory characteristics of treatment resistance, renal relapse and progression to end-stage renal disease (ESRD) in adolescents and young adults with LN.Patients and methodsEighty-five biopsy-proven LN patients were examined; SLE disease activity and renal damage were evaluated at baseline and followed up at 6 and 12 months. Laboratory and immunology profiles were assessed. Patients were evaluated for predictors of treatment response, renal flares, and renal survival.ResultsThe patients mean age was 15.12 ± 4.53 years. Female/male ratio was 10.5:1. 12.9% had treatment resistance, 87.1% achieved remission: complete (CR 31.8%) and partial (PR 55.2%) within 1st year. 27 (31.8%) developed a relapse within the 1st year (9 after CR and 18 after PR). Nephrotic range proteinuria persisted in 24 (28.2%) patients (13 PR and the 11 non-responders). Baseline hypertension (p = 0.034), persistent nephrotic range proteinuria (<0.001) and PR (p < 0.001) were predictive for renal flares. Treatment resistance (p = 0.021), disease relapse (p < 0.001), persistent nephrotic range proteinuria (p < 0.001) were predictors of ESRD, especially in males (p = 0.035). Autoimmune profile and histopathology class showed insignificant differences among groups.ConclusionPrevention and aggressive management of hypertension, proteinuria and renal flares is expected to prevent progression to ESRD in lupus nephritis in adolescent and young adult SLE patients.     

New-onset systemic lupus erythematosus during pregnancy

Few studies have been published focusing on the clinical features of new-onset systemic lupus erythematosus (SLE) during pregnancy. This study examined the clinical characteristics of SLE during pregnancy or puerperium. The clinical characteristics and serological parameters of 48 patients with onset of SLE during pregnancy were retrospectively compared with those of age-matched new-onset SLE patients who were diagnosed in a period of more than 12 months without pregnancy (n?=?65) and age-matched preeclampsia patients (n?=?48). SLE tended to occur during the first and second trimesters (33 and 42 %, respectively). Lupus nephritis (LN) and severe thrombocytopenia were more commonly seen in new-onset SLE during pregnancy than in patients without pregnancy (68.8 vs 35.4 % and 25 vs 9.2 %, respectively, p?<?0.05). However, pregnant patients had lower frequency of fever, arthritis, arthralgia, alopecia, oral ulcer, and hypocomplementemia than the nonpregnant controls (p?<?0.05). Compared to LN patients without pregnancy (n?=?23), LN patients with pregnancy (n?=?33) had more prominent proteinuria and nephrotic syndrome (p?<?0.05). On the other hand, when compared to patients with preeclampsia, patients with new-onset SLE during pregnancy had early onset of symptoms during gestation and were characterized by presence of fever, malar lesion, autoantibodies, hypocomplementemia, hyperuricemia, active urinary sediment, and multi-organ involvement. In conclusion, patients with their first onset of lupus during pregnancy generally have more severe disease with higher prevalence of renal and platelet involvement.     

Anti-C1q antibodies and antiendothelial cell antibodies in systemic lupus erythematosus – relationship with disease activity and renal involvement

The aim of this study was to investigate the relationship between the presence and titre of antibodies against C1q (anti-C1q Ab) and disease activity and renal involvement in patients with systemic lupus erythematosus (SLE). Anti-C1q Ab were measured in 79 patients with SLE (70 women and 9 men; mean age 41.7 years; mean disease duration 8.4 years): 19 patients had active disease with lupus nephritis, 8 active disease without nephritis, 26 inactive disease with nephritis and 26 inactive disease without nephritis. Anti-dsDNA antibodies (EIA and immunofluorescence), antiendothelial cell antibodies (AECA) and complement levels (C3, C4, total haemolytic complement activity) were determined in parallel. Anti-C1q Ab were positive in 49%, anti-dsDNA Ab in 61% and AECA in 19% of the patients, respectively. Significantly higher titres of anti-C1q Ab were found in patients with active disease compared with those with inactive SLE (P < 0.01). Serum levels of anti-C1q Ab showed a positive correlation with anti-dsDNA Ab and SLEDAI score (P < 0.01) and a negative correlation with C3 (P < 0.05), C4 (P < 0.01) and CH50U (P < 0.01). The presence of anti-C1q Ab was not different between patients with or without nephritis. In patients with (P < 0.05) and without nephritis (P < 0.01) the frequency of anti-C1q Ab was significantly higher in active patients compared with inactive patients. Both anti-C1q and anti-ds-DNA Ab were detectable in 74% of patients with active nephritis but only in 30% of all other patients (P=0.001). None of the patients with active nephritis was negative for anti-C1q and anti-dsDNA Ab, whereas 37% of the patients without active nephritis were negative for both antibodies (P < 0.01). Sensitivity, specificity, positive and negative predictive values for active lupus nephritis among SLE patients were 100%, 50%, 51.9% and 100% for anti-dsDNA Ab (EIA) and 74%, 70%, 57% and 89.4% for positive findings of both anti-dsDNA and anti-C1q Ab. The presence and titre of anti-C1q-Ab in SLE are related to disease activity. Absence of anti-dsDNA Ab excludes active nephritis; positive findings of both anti-dsDNA Ab and anti-C1q Ab are of relatively high specificity for active nephritis.     

Serum uric acid levels are associated with lupus nephritis in patients with normal renal function

Uric acid has been recognised as a potential marker of endothelial dysfunction and kidney disease but there are scarce data about its importance in systemic lupus erythematosus (SLE) nephritis. This study aimed to evaluate serum uric acid (UA) levels in lupus nephritis (LN), by comparing SLE patients with normal renal function, with and without nephritis. Forty-six female SLE patients were consecutively selected and divided in two groups according to renal activity at the evaluation: presence of a recently diagnosed lupus nephritis (LN+, n?=?18) and absence of lupus nephritis (LN?, n?=?28). Age-matched healthy women were selected (CONTROL, n?=?28). Patients with gout, creatinine clearance lower than 80 ml/min and use of drugs that interfere in UA were excluded. Laboratory and clinical data were analysed by appropriate tests. A multivariate analysis was performed, and a receiver operating characteristic (ROC) curve was plotted, and the area under the curve was calculated to assess the diagnostic strength of UA in LN. The mean age was similar among LN+, LN? and CONTROL groups (32.44?±?6.09 vs. 30.68?±?5.36 vs. 30.86?±?5.00 years, p?=?0.52). UA was significantly higher in LN+ compared to LN? (5.54?±?1.67 vs. 3.65?±?1.090 mg/dL, p?<?0.001) and CONTROL (5.54?±?1.67 vs. 3.92?±?0.95 mg/dL p?<?0.001). Multivariate analysis confirmed that high UA was an independent variable related to LN (p?<?0.001). The cut-off value for UA using the ROC curve was 4.47 mg/dL (AUC 0.86, p?=?0.00004, CI 95% 0.75–0.96). Lupus nephritis was associated with higher UA. Hyperuricemia as a predictor of renal damage in SLE needs to be evaluated in further studies.