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.     

Serum beta2-microglobulin level in systemic lupus erythematosus patients: Relation to disease activity

Aim of the workTo assess the level of β2-microglubulin (β2M) in systemic lupus erythematosus (SLE) patients and its association with disease activity and other disease parameters.Patients and methods40 SLE patients and 22 matched controls were studied. Serum β2M was assessed using enzyme-linked immunosorbent assay (ELISA). SLE Disease Activity Index (SLEDAI) and the damage index were assessed.ResultsThe patients were 36 females and 4 males (F:M 9:1) with a mean age of 28.5 ± 7.9 years and disease duration of 6.7 ± 3.3 years. The SLEDAI was 9.3 ± 5.2 and the damage index 1.83 ± 1.84. The mean level of serum β2M was significantly higher in SLE patients (6.42 ± 2.46 mg/L) than control (2.47 ± 0.4 mg/L) (p < 0.01).The serum level of β2M was significantly higher in patients with nephritis (n = 22) (7.45 ± 2.47 mg/L) compared to those without (n = 18) (5.17 ± 1.82 mg/L)(p = 0.002), And it was similar in those with and without arthritis (7.24 ± 2.3 mg/L vs 5.88 ± 2.4 mg/L (p0.07).The β2M significantly correlated with disease activity (r = 0.86, p 0.001), serum creatinine (r = 0.52, p > 0.001), urea (r = 0.63, p < 0.001), 24 h urinary protein (r = 0.56, p < 0.001), hematuria (r = 0.4, p < 0.01) and pyuria (r = 0.41; p < 0.01), ESR (r = 0.48; p < 0.01) and inversely with hemoglobin level (r = ?0.34; p = 0.03). No significant correlation was found with C-reactive protein or with disease damage. Serum (β2M) significantly predicted nephritis and disease activity (sensitivity 63.6 %, specificity 77.8 %; p < 0.001 and 95 %CI: 0.25–0.41; p < 0.001 respectively).ConclusionSerum β2M is significantly associated with disease activity and lupus nephritis, suggesting that serum β2M may serve as a potential biomarker to monitor the disease activity and predicting lupus nephritis. However its association to disease severity needs further longitudinal studies.     

Serum interleukin-18 levels in patients with systemic lupus erythematosus: Relation with disease activity and lupus nephritis

Aim of the workTo further investigate the possible role of IL-18 in the pathogenesis of systemic lupus erythematosus (SLE) and development of lupus nephritis (LN), and to explore its relationship with pathological classes of LN, degree of acute renal activity and chronic damage.Patients and methodsForty-one SLE patients with LN, thirty-one lupus non-nephritis patients and fifteen age and sex matched healthy controls were enrolled in this study. SLE patients were subjected to disease activity assessment by SLEDAI, renal disease activity assessment by the Systemic Lupus International Collaborating Clinics (SLICC) Renal Activity Score, laboratory investigations including measurement of serum interleukin-18 using Enzyme Linked Immunosorbent Assay. Renal biopsy was obtained from LN patients and pathological classification was made according to World Health Organization (WHO) criteria. Analysis of activity and chronicity indices was done on these biopsy specimens.ResultsSerum levels of IL-18 were significantly higher in patients with LN than lupus non-nephritis patients and healthy controls (p < 0.001). There were significant correlations between IL-18 and SLEDAI (p = 0.002), proteinuria (p = 0.027), renal activity score (p = 0.003) and activity index (p = 0.039) in patients with LN. There was no significant difference in the serum levels of IL-18 between WHO classes of LN.ConclusionIL-18 appears to have a pathogenic role in the development of SLE and plays a crucial role in triggering inflammation in LN. Serum IL-18 levels could be a useful biomarker to assess the activity of renal disease in SLE.     

Association of IgA anti-dsDNA antibodies with vasculitis and disease activity in systemic lupus erythematosus

Previously it has been suggested that the presence of antibodies against dsDNA of the IgA class may define a subset of systemic lupus erythematosus (SLE) patients suffering from nephritis and arthritis. Therefore, these autoantibodies were measured in sera of 352 patients with SLE, 81 blood donors, and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgA anti-dsDNA antibodies were found in 19.9% of the sera from patients with SLE, 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 36 laboratory parameters was calculated. IgA anti-dsDNA antibodies were found to be associated with parameters of disease activity such as elevated erythrocyte sedimentation rate and consumption of complement component C3, and the clinical parameters vasculitis, acral necrosis and erythema, but not with nephritis and arthritis. Therefore, IgA anti-dsDNA antibodies define a subset of SLE patients, and monitoring of IgA anti-dsDNA antibodies may be helpful as a prognostic parameter in patients with SLE. Received: 12 April 1998 / Accepted: 24 April 1998     

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.

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.     

Clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus patients

The aim of this study was to investigate the clinical significance of antinucleosome antibodies in Tunisian systemic lupus erythematosus (SLE) patients. IgG antinucleosome antibodies were detected by a qualitative enzyme immunoassay (immunodot) in the sera of SLE patients at onset of disease. The patients were divided into two groups according to the result of the antinucleosome antibodies test: positive (group A) and negative (group B). The two groups were also evaluated for clinical and biological parameters. Of 84 patients with SLE, 66 (78.6%) had antinucleosome antibodies. Among 21 patients negative for anti-double-stranded DNA (anti-dsDNA), 5 (23.8%) were antinucleosome positive. The most common initial features were haematological disorders (80.1%) and arthritis or arthralgias (79.8%). Renal disorders, observed in 59.5% of SLE patients, were more common in group A compared to group B (65 vs 38%) (p=0.04). The European Consensus Lupus Activity Measurement (ECLAM) mean score was higher in group A (6.42) than in group B (4.44) (p=0.002). Antinucleosome antibodies were positive in nearly one-fourth of SLE patients negative for anti-dsDNA. We found a correlation between antinucleosome antibodies, nephritis and SLE disease activity. Therefore, the determination of circulating antinucleosome antibodies could be a useful parameter for early diagnosis and follow-up of SLE patients.     

Antinuclear antibodies measured by enzyme immunoassay in patients with systemic lupus erythematosus: relation to disease activity

To evaluate the correlation between measurements of antinuclear antibodies serum levels by enzyme immunoassay (ANA-EIA), and the degree of systemic lupus erythematosus disease activity. To retest the performance of the test compared to measurement of antinuclear antibodies by immunofluorescence (ANA-IIF). Eighty-five sera from 71 patients with SLE were tested. Demographic, clinical, laboratory, and SLEDAI status were collected. The sera were tested for ANA-EIA and by ANA-IIF at 1:40 and 1:160 dilutions. Serum levels of ANA-EIA were compared to the overall SLEDAI score and to each of its components. A SLEDAI score of ≥6 was considered clinically significant. The sera of fifty-one healthy volunteers served as controls. Serum levels of ANA-EIA were significantly higher in patients with a SLEDAI score of ≥6 compared to the group of patients with a SLEDAI score of <6 (P = 0.004). High serum levels of ANA-EIA correlated significantly with elevated anti DS-DNA antibodies (P < 0.001), low C₃ or C₄ levels (P < 0.001), pyuria (P < 0.011), arthritis (P = 0.019), and new rash (P = 0.019). Levels of ANA-EIA were significantly higher in patients tested positive by IIF compared to those who tested negative. Higher serum levels of ANA-EIA correlated with clinically significant disease activity in patients with SLE. Higher serum levels of ANA-EIA also correlated with some single items of the SLEDAI. The results also reiterated the validity of ANA-EIA testing in patients with SLE. Further longitudinal studies are needed in order to test the hypothesis that serum ANA-EIA levels might reflect fluctuations in disease activity.     

Resistin in systemic lupus erythematosus: Relation to lupus nephritis and premature atherosclerosis

BackgroundLupus nephritis (LN) is one of the most severe complications of SLE. SLE patients have a greater risk of developing premature atherosclerosis. Resistin is an adipocyte-secreted peptide. It has pro-inflammatory and atherogenic effects.Aim of the workTo assess the serum levels of resistin in SLE patients and to evaluate it as a marker of nephritis and premature atherosclerosis.Patients and methodsThis study included 50 SLE nonpregnant female adult (mean age 23.1 ± 6.9 years) patients as well as 40 healthy volunteers matched in age and sex as a control group. Serum levels of resistin were assayed using enzyme-linked immunosorbent assay (ELISA). All patients and controls underwent laboratory investigations and carotid duplex. Disease activity was assessed using SLE Disease Activity Index (SLEDAI). Renal biopsy was performed for SLE patients with LN.ResultsThere was a highly statistically significant increase in mean serum resistin levels (14.1 ± 3.88 ng/ml) in patients versus the control group (6.44 ± 1.34 ng/ml) being more obvious in those with LN. Resistin had a significant positive correlation with markers of inflammation, SLEDAI and carotid intima media thickness (CIMT).ConclusionSerum level of resistin may serve as a marker of LN and atherosclerosis in SLE patients. A more aggressive control of the underlying inflammatory process along with the control of traditional risk factors (hypertension and cholesterol) may be beneficial in reducing the risk factors of renal and atherosclerotic involvement in SLE. Therapeutic approaches with drugs that target resistin might be useful in the treatment of SLE.     

Soluble and membranous endothelial protein C receptor in systemic lupus erythematosus patients: Relation to nephritis

Aim of the work

To investigate the role of endothelial protein C receptor (EPCR) (membrane and soluble forms) as a biomarker of lupus nephritis (LN) in systemic lupus erythematosus (SLE) patients and to study its relation to the prognosis and response to treatment.

Interleukin-23 serum level in systemic lupus erythematosus patients: Relation to disease activity and different disease parameters

Aim of the workTo assess serum level of interleukin 23 (IL-23) in systemic lupus erythematosus (SLE) patients and to evaluate its association with disease parameters and activity.Patients and methodsThe study involved 40 SLE patients and 40 controls. The SLE disease activity index (SLEDAI) and damage index (SDI) were assessed. Serum level of IL-23 was measured by enzyme linked immunosorbant assay (ELISA).ResultsPatients were 38 females and 2 males (F:M 19:1),with a mean age of 31.3 ± 7.5 years (17–50 years) and disease duration 4.8 ± 2.9 years (1–13 years). Their mean SLEDAI was 14.3 ± 6.8 (3–32) and SDI 0.4 ± 0.5 (0–2). 85% of patients had photosensitivity, alopecia in 60%, malar rash in 57.5%, oral ulcers 52.5%, arthralgia/arthritis 47.5%, serositis and lupus nephritis in 27.5%, discoid rash in 22.5% and neuropsychiatric in 2.5%. Mean serum level of IL-23 was significantly elevated in patients (107.9 ± 17.3 ng/L; 72.7–165.5 ng/mL) compared to controls (91.6 ± 19.1 ng/L; 57.6–140.3 ng/mL; p < 0.001). IL-23 was significantly elevated in patients with oral ulcers (p = 0.03), arthritis (p < 0.001), lupus nephritis (p = 0.01), alopecia (p = 0.02) and positive anti-dsDNA (p < 0.001). IL-23 significantly correlated with SLEDAI (r = 0.89, p < 0.001), complement C3 (r = -0.55, p < 0.001) and C4 (r = -0.5, p = 0.001). IL-23 could significantly predict SLE at a cut-off 93.1 ng/L (sensitivity 80% and specificity 55%).ConclusionIL-23 may be involved in the pathogenesis of SLE; especially in renal, mucocutaneous and musculoskeletal manifestations and it can be used as a disease activity biomarker. These findings support the possibility of its use as a therapeutic target in SLE.     

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     

Clinical and serological correlates of antinucleosome antibodies in South Africans with systemic lupus erythematosus

Antinucleosome antibodies (AnuA) are increasingly recognized as an important biomarker in the diagnosis and subset stratification of patients with systemic lupus erythematosus (SLE). The aim of the study was to determine the sensitivity, specificity, and clinico-serological correlates of AnuA in black South Africans with SLE. We performed a cross-sectional study of 86 SLE patients attending a tertiary center and 87 control subjects. AnuA were tested using a second-generation enzyme-linked immunosorbent assay (ELISA). The sensitivity, specificity, positive predictive value, and negative predictive value of AnuA were 45.3, 94.3, 88.6, and 63.6%, respectively. The presence of AnuA were strongly associated with the co-presence of anti-dsDNA antibodies (OR = 3.4, p < 0.0005) and antihistone antibodies (OR = 15.7, p < 0.00001). Patients who were seropositive for AnuA were more likely to have skin involvement (discoid lupus and/or malar rash) and had higher SLE disease activity index (SLEDAI) scores and Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage scores (p < 0.05). IgG anticardiolipin antibody (aCL) levels showed a significant correlation with AnuA ratios (p < 0.01). Our findings provide further evidence that AnuA are a sensitive and specific diagnostic biomarker in SLE. Moreover, our finding that the presence of AnuA, but not anti-dsDNA antibodies, are associated with worse SLICC/ACR damage scores suggest that AnuA may have a role in predicting disease outcome. The correlation between IgG aCL and AnuA is a novel finding that merits further studies to determine possible common peptide specificities of the antibodies.     

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.     

Implications of blood indices in systemic lupus erythematosus patients: Two feasible determinants of disease activity and lupus nephritis

Aim of the workTo investigate whether or not neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) may by indicators of disease activity in systemic lupus erythematosus (SLE) with and without lupus nephritis (LN).Patients and methodsThis research was carried out on 40 adult SLE patients (20 with LN and 20 without) and 20 controls. The NLR and PLR were calculated. The SLE disease activity index (SLEDAI) was assessed.ResultsThe mean age of the patients was 36.2 ± 7.6 years, 38 females and 2 males (F:M 19:1), with a disease duration of4.3 ± 1.2 years. The mean SLEDAI was 15.1 ± 4.7 being significantly higher in those with LN (17.5 ± 3.5) compared to those without (12.6 ± 4.6) (p = 0.001). The mean NLR (6.1 ± 2.1) and PLR (236.6 ± 86.9) were significantly increased in patients compared to the control (2.7 ± 1.2 and 125.2 ± 38.8 respectively) (p < 0.001). The NLR and PLR were both significantly related to the serum creatinine (r = 0.35, p = 0.03 and r = 0.5, p = 0.001) and SLEDAI (r = 0.36, p = 0.03 and r = 0.34, p = 0.03 respectively). NLR can significantly predict activity of SLE at cut off 5.6 with a sensitivity 80%, specificity 65% (p = 0.007) and PLR at cut off 217 with sensitivity 75%, specificity 65% (p = 0.035). The NLR can significantly predict LN at cut off 3.6 (sensitivity 80%, specificity 40%; p = 0.007) and PLR at cut off 186 (sensitivity 70%, specificity 60%; p = 0.035).ConclusionThere is a remarkable link between PLR and NLR with SLEDAI. Thus, both may serve as promising affordable indicators of inflammation in SLE. The notable relation to LN may signal renal involvement in patients with SLE.     

Kidney disease in systemic lupus erythematosus

Summary Glomerulonephritis is a major determinant of outcome in patients with systemic lupus erythematosus. Persistently active lupus nephritis imposes serious threats of end-stage renal failure and cardiovascular morbidity. Sustained corticosteroid treatment has been characterized as having an uncertain net benefit on the control of lupus nephritis, mainly because these drugs have relatively weak efficacy and they have been shown to confer their own set of cardiovascular risk factors. Controlled trials of corticosteroids, azathioprine and cyclophosphamide have demonstrated that the best control of clinical activity of proliferative lupus nephritis is attained with cyclophosphamide. To date, intermittent pulse cyclophosphamide treatment has produced the most facorable balance of efficacy and toxicity in patients with lupus nephritis.     

Anti-topoisomerase I antibodies in systemic lupus erythematosus as a marker of severe nephritis

The authors report nine patients with systemic lupus erythematosus associated with anti-topoisomerase I antibodies (ELISA test) without features of systemic sclerosis. These antibodies were correlated with the disease activity and might be a marker of the severity of the closely related to difusse proliferative glomerulonephritis.     

Urinary podocalyxin and nephrin levels as biomarkers in lupus nephritis patients: Relation to renal involvement and disease activity

Aim of the workTo evaluate the impact of systemic lupus erythematosus (SLE) on urinary levels of podocalyxin and nephrin and to determine their relationship to renal biopsy and disease activity in lupus nephritis (LN) patients.Patients and methodsThe study included 50 LN patients with their renal biopsy classified according to the international society of nephrology. Disease activity was determined using the British Isles Lupus Assessment Group (BILAG). All patients underwent clinical and laboratory evaluation. Urine samples were collected for the assessment of urinary podocalyxin (UPx) and nephrin (UN) by ELISA and for the estimation of protein (UP) and creatinine (Cr) concentrations. The UPx:Cr, UN:Cr and UP:Cr ratios were calculated.ResultsUrinary levels of podocalyxin (593.8 ± 282.2 ng/ml), nephrin (304.1 ± 236.8 ng/ml) and protein (2.36 ± 0.56 g/l) were significantly higher, while urinary creatinine levels (101.4 ± 28.7 mg/l) lower in LN patients compared to control (38.1 ± 9 ng/ml, 19.2 ± 4.1 ng/ml, 0.34 ± 0.13 g/l and 155.4 ± 26.7 mg/l; p = 0.0008, p = 0.0003, p = 0.00002 and 0.0009, respectively). Consequently, UNCr, UPxCr and UPCr ratios were significantly higher in patients compared to control. There was a significant correlation of the estimated ratios with the LN class and with the BILAG scores being most significant with UPx:Cr ratio. ROC curve and regression analyses defined UPx:Cr ratio as the specific significant predictor of pathological LN grade.ConclusionSLE deleteriously affects fine glomerular structure as reflected by increased urinary levels of podocyte-related proteins; podocalyxin and nephrin. Urinary podocalyxin/creatinine ratio significantly predicts the pathological impact of SLE on the kidney and could be used as a non-invasive marker for such effect and its progression.     

Elevated interleukin-18 levels correlated with disease activity in systemic lupus erythematosus

The aim of this study was to determine the serum interleukin-18 (IL-18) levels in patients with systemic lupus erythematosus (SLE) and to assess their relationship with disease activity. Thirty-five patients with SLE and 35 age- and sex-matched controls were enrolled in this study. Paired serum samples were collected from all the patients with SLE, both at active stage before treatment and at the stable stage after treatment. The serum IL-18 levels were determined using ELISA and their correlations with the disease activity, measured using the SLE Disease Activity Index (SLEDAI) and laboratory parameters such as anti-dsDNA antibody, CH50, C3, C4, and circulating immune complex levels, were analyzed. The serum IL-18 levels in patients with SLE were significantly higher than those in the controls, particularly when the disease status was active (mean±SD: active stage, 721.23±360.15 pg/ml; inactive stage, 343.68±317.78 pg/ml; controls, 113.98±13.22 pg/ml, p<0.05). The IL-18 levels measured at the active stage before treatment correlated well with SLEDAI (r=0.41, p<0.05) and anti-dsDNA antibody titer (r=0.35, p<0.05). When we compared the changes of the IL-18 level and those of parameters reflecting the disease activity between the active stage and the stable stage of the disease, it was found that the changes in IL-18 level correlated well with the changes of SLEDAI score during the patients disease course (r=0.39, p<0.05). In conclusion, the serum IL-18 levels were elevated in patients with SLE, and these increased levels correlated well with SLE disease activity.Abbreviations CIC Circulating immune complex - IFN Interferon - IL Interleukin - SLE Systemic lupus erythematosus - TNF Tumor necrosis factor     

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