Lupus Nephritis Group Research Articles

Low level of circulating basophil counts in biopsy-proven active lupus nephritis.

Basophils have been shown to be important players in promoting lupus nephritis (LN). However, the relationship between circulating basophil counts and renal pathology activity of LN remains unclear. In this retrospective study, 159 clinical and pathology samples from patients with biopsy-proven LN were analyzed. The renal activity and classification were evaluated according to renal pathology. The correlations between circulating basophil counts and renal pathology activity index were assessed. Overall, circulating basophil counts correlated with total systemic lupus erythematosus disease activity index (SLEDAI) score (r=-0.31), renal SLEDAI score (r=-0.35), activity index (AI) score(r=-0.40), and renal histologic activity parameters (p<0.05, respectively). Compared with systemic lupus erythematosus (SLE) non-LN patients, the LN group had lower basophil counts (0.007±0.007 vs. 0.011±0.010×109/L, p=0.04). Subgroup analyses revealed that the circulating basophil counts in group B (AI>8) were significantly lower than that in group A (AI≤8) (0.004±0.006 vs. 0.009±0.009×109/L, p<0.001). The difference was still significant when eliminating the influence of SLEDAI. Significant differences were found in circulating basophil counts among LN pathology classification groups (p<0.01). Groups of classes III, IV, and V were more likely to have lower circulating basophil counts when compared with group of class I/II (p<0.05). These findings suggest a potential role of circulating basophil counts as a convenient and helpful marker for renal activity of LN.

Study for the Relationship between Lupus Nephritis and Anti-C1q Antibodies

Background: lupus nephritis (LN) is an inflammation of the kidney caused by systemic lupus erythematosus (SLE), a disease by the immune system. Anti-C1q antibodies have been found in many different systemic autoimmune diseases, they are strongly linked to immune complex disorder most prominently SLE and severe rheumatoid arthritis and have been suggested to be closely associated with lupus nephritis (LN). Generally anti-dsDNA antibodies have been acknowledged as an important tool in the diagnosis of SLE, however their predictive value as to the activity of the disease remains controversial, on the contrary anti-C1q antibodies appear to have a clear-cut relationship with renal complications of SLE not only have they been shown to play a pathogenic role in the development of lupus nephritis but also their serum levels correlate with the presence of active proliferation lupus nephritis. Aim of the study: this study aimed to investigate association between serum titer of anti-C1q antibody and disease manifestation of SLE. Methodology: the study was carried out in three different groups: healthy group, rheumatoid arthritis group and lupus nephritis group. All groups were subjected to determination of anti-C1q antibody, blood urea nitrogen (BUN) and serum creatinine. Results: there was no significant difference in BUN levels between the normal and rheumatoid arthritis groups in contrast there was a highly significant difference in BUN between the normal and lupus groups also, between the rheumatoid arthritis and lupus nephritis groups (p˂0.001). No significant difference was detected in serum creatinine levels between the normal and rheumatoid arthritis groups in there was a highly significant difference in serum creatinine between the normal and lupus groups and also between the rheumatoid arthritis and lupus nephritis groups (p˂0.001). No significant difference was realized in serum anti-C1q antibodies levels between the normal and rheumatoid arthritis groups in contrast there was a highly significant difference in serum anti-C1q antibodies between the normal and lupus groups and also between rheumatoid arthritis and lupus nephritis groups (p˂0.001). In the control group and rheumatoid arthritis groups, only BUN showed a highly significant positive correlation with serum creatinine concentration (r=0.906, r=0.404) and (P˂0.001, P˂0.05) respectively, while in lupus nephritis group, BUN showed a highly positive correlation with serum creatinine concentration (r=0.773, P˂0.001) also serum creatinine concentration showed a positive concentration with serum anti-C1q antibody (r=0.513, P˂0.05). Conclusion: the present study suggested that anti-C1q antibody might be a new parameter for the development of lupus nephritis since the increased of anti-ds DNA antibody and hypocomplementemia (C3 and C4) are serological markers of SLE activity, but they are not enough to identify which organ may be affected, while anti-C1q antibody either alone or in combination with other serological markers could give information of the diagnosis of a renal flare with 100% sensitivity and specificity.

Serum levels of adiponectin and leptin as biomarkers of proteinuria in lupus nephritis.

IntroductionThere are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis.ObjectiveThe aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN).MethodsIn a cross-sectional study, 103 women with systemic lupus erythematosus (SLE) were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN). A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN.ResultsWe found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02), whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07). Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001), but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01–1.12; p = 0.02). Instead, leptin was not associated with LN.ConclusionThese findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse.

Relevant genetic polymorphisms and kidney expression of Toll-like receptor (TLR)-5 and TLR-9 in lupus nephritis.

Toll-like receptor (TLR) genetic polymorphisms may modify their expression causing inflammatory disorders and influencing both susceptibility and severity of lupus erythematosus. We aim to determine whether TLR-5 and TLR-9 gene polymorphisms are implicated in the susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN) and to evaluate their expressions and distributions in renal LN patients' biopsies. The frequencies of two SNP in the TLR-9 gene and one in the TLR-5 gene was examined in 106 SLE patients (among them 37 LN patients) and in 200 matched controls by polymerase chain reaction-restriction fragment-length polymorphisms (PCR-RFLP) analysis. TLR-9 and TLR-5 expressions were assessed by reverse transcription (RT)-PCR and immunohistochemistry carried on LN renal biopsies compared to healthy renal tissue. A significant genotypic and allelic association was revealed between TLR-9-rs352140 and both SLE and LN (P < 0·05). The TLR-9 transcript level was significantly higher in LN biopsies compared to control (P < 0·05). This increase was observed histochemically in the tubulointerstitial compartment. TLR-9 was detectable in LN glomeruli patients but not in normal control glomeruli. No allelic nor genotype association was found with TLR-5-rs5744168 in SLE. but the T allele and the TT genotype were raised significantly in the LN group (P < 0·05). A significant increase in TLR-5 gene expression in LN biopsies, which contrasted with normal kidneys (P < 0·05), was confirmed by an intense and diffuse staining for TLR-5 only in LN tubules (P < 0·05). Our data show that TLR-5 and TLR-9 are susceptible genes to LN and that their expression is dysregulated in LN patients' kidneys, supporting a role of these mediators in the pathogenesis of LN.

Plasma ADAMTS-13 activity in proliferative lupus nephritis: a large cohort study from China.

Objectives The aim of this study was to investigate plasma ADAMTS-13 activity in patients with proliferative lupus nephritis and to evaluate the role of clinical, laboratory and pathological features, especially the vascular lesions in lupus nephritis. Methods Plasma samples from 163 class III and IV lupus nephritis patients confirmed by biopsy examinations and 98 normal controls were collected. ADAMTS-13 activity was evaluated by a residual collagen binding assay. IgG autoantibodies against ADAMTS-13 were detected by ELISA using recombinant ADAMTS-13 as a solid-phase ligand. Levels of vWF were measured by ELISA. Their associations with clinical, laboratory and pathological features were further assessed. Results Plasma ADAMTS-13 activity in lupus nephritis patients was significantly lower than that in normal controls (84 ± 21% vs. 90 ± 13%, p = 0.005). IgG ADAMTS-13 autoantibodies were detected in only three patients. The plasma level of vWF was significantly higher in the lupus nephritis group than in normal controls (1.00 ± 0.79 vs. 0.70 ± 0.30, p = 0.025). Plasma ADAMTS-13 activity was negatively correlated with the level of serum creatinine and proteinuria ( r = -0.354, p < 0.001; r = -0.200, p = 0.011, respectively). Patients with a higher level of ADAMTS-13 activity had significantly higher levels of factor H (401.51 ± 183.01 µg/ml vs. 239.02 ± 155.45 µg/ml, p = 0.005). Plasma ADAMTS-13 activity was negatively associated with total pathological AI scores ( r = -0.326, p < 0.001), endocapillary hypercellularity ( r = -0.419, p < 0.001), cellular crescents ( r = -0.274, p < 0.001), subendothelial hyaline deposits ( r = -0.266, p = 0.001), interstitial inflammatory cell infiltration ( r = -0.304, P < 0.001), tubular atrophy ( r = -0.199, p = 0.011), acute glomerular vascular lesions ( r = -0.344, p < 0.001) and acute renal vascular lesions ( r = -0.338, p < 0.001). No association was found between level of vWF and plasma ADAMTS-13 activity ( r = 0.033, p = 0.671). Low level of ADAMTS-13 activity was a risk factor for renal outcomes ( p = 0.039, HR = 0.047, 95% CI: 0.120-1.005). Conclusions Decreased ADAMTS-13 activity was found in patients with proliferative lupus nephritis, and plasma ADAMTS-13 activity was closely associated with renal injury indices, especially pathological vascular scores. The role of ADAMTS-13 in the disease remains to be further investigated.

Genetic variants in FH are associated with renal histopathologic subtypes of lupus nephritis: a large cohort study from China.

Objective Genetic variants in FH (complement factor H) were reported to associate with susceptibility to systemic lupus erythematosus (SLE). This study proposed that the genetic defects of FH in the susceptibility and in the development of lupus nephritis might be different. Methods This study enrolled 334 lupus nephritis patients, 269 SLE patients without clinical renal involvement and 350 controls. Two-step genotyping was performed. First, all the exons of the FH gene were fully sequenced in 100 lupus nephritis patients and 100 healthy controls. Second, genotyping of three common variants reported to be functional, rs1061170, rs800292 and rs6677604, was conducted in all the recruited individuals. Further, analysis of their associations with SLE/lupus nephritis susceptibility and the clinico-pathological parameters in the lupus nephritis group was performed. Results No significant differences were observed in allele and genotype frequencies of the three single nucleotide polymorphisms between lupus patients and controls. There was a significantly higher ratio of CC/CT genotypes of rs1061170 in lupus nephritis patients with class III than in the other two classes (class III vs. class IV vs. class V: 21.0% vs. 9.7% vs. 9.4%; P = .044). The rs6677604-GG genotype was observed to be associated with the absence of anti-ds DNA antibody ( P = .021), and the rs800292-TT genotype was associated with a higher level of circulating C3 ( P = 0.20) in lupus nephritis. Conclusion In an independent cohort, this is the first genetic association analysis focusing on FH genetic variants in Chinese lupus nephritis patients. It was found that the variants in the FH gene might affect the histopathologic subtypes and some clinical features of the disease.

Neutrophil to Lymphocyte Ratio and Mean Platelet Volume as Inflammatory Indicators in Systemic Lupus Erythematosus Nephritis.

This study aims to evaluate the role of neutrophil to lymphocyte ratio (NLR) and mean platelet volume (MPV) as activation and inflammatory markers in systemic lupus erythematosus (SLE) patients with nephritis. A total of 108 SLE patients (8 males, 100 females; mean age 35.3±10.2 years; range 16 to 64 years) including 78 patients with renal involvement (8 males, 70 females; mean age 33.9±10.6 years; range 16 to 64 years) (SLEn+ group) and 30 patients without renal involvement (30 females; mean age 39.1±8.2 years; range 22 to 55 years) (SLEn- group) were included in this retrospective study. All patients' clinical characteristics and laboratory data which include erythrocyte sedimentation rate, C-reactive protein, white blood counts, neutrophil counts, lymphocyte counts, platelet counts, and MPV levels were obtained from medical records. The laboratory data at the highest proteinuria periods of the patients with renal involvement were recorded. Mean MPV (SLEn+ =9.1±2.2, SLEn- =7.9±1.2, p=0.001) and NLR (SLEn+ =5.9±5.9, SLEn- =2.6±2.5, p<0.001) values were significantly higher in lupus nephritis group. Besides, a positive correlation between NLR and C-reactive protein was found in lupus nephritis group (r=1.97, p=0.045). Based on receiver operating characteristic curve with area under the curve of 0.76, cutoff NLR value of 1.93 had 83% sensitivity and 54% specificity [95% confidence interval, 0.66-0.85] in differentiating SLE patients with or without nephritis. Neutrophil to lymphocyte ratio and MPV may be discriminative for lupus nephritis. Also, NLR may be a predictor of lupus nephritis. Both MPV and NLR values may be affected by a great number of factors; therefore, further prospective studies are needed to evaluate the use of these parameters in SLE.

Assessment of microRNA profile of kidney biopsies of patients with lupus nephritis

Background: The changes in some epigenetic elements such as microRNAs result in aberrant immune responses leading to production and secretion of nephritogenic autoantibodies as the main fundament of lupus nephritis (LN). Objectives: The present study aimed to assess the miRNA profile of kidney biopsies in patients with LN with the purpose of describing the critical role of these elements in LN creation. Patients and Methods: In this case-control single center study 11 patients who suffered LN (as the case group) and 11 patients with normal kidney function who were candidate for nephrectomy due to cancer or cyst (as the control group) were included. Kidney biopsies were taken from all LN and control subjects. RNA was extracted and converted to cDNA, then the cDNA was evaluated using NANODROP and then intra-renal expression of candidate miRNAs were quantified in the two groups. In the present study, four topranked miRNAs, miR-638, miR-146a, miR-198, and miR-731 were selected for qRT-PCR. Results: Consistent with the microarray data, we found no significant difference in the expression of all miRNAs between LN and control groups. Using REST 2009 software, we did not also reveal any difference in expression of four miRNAs studied between the patients with LN and those without LN in both parametric and nonparametric patterns. Conclusions: The expression of miR-638, miR-146a, miR-198, and miR-731 may not be related to occurrence of LN in Iranian population.

Complement Alternative Pathway׳s Activation in Patients With Lupus Nephritis

ObjectiveThe aim of this study was to detect the spectrum of complement activation pathways in circulation and to assess their correlations with clinical and pathologic features in a large lupus nephritis cohort from China. Materials and MethodsPlasma levels of C1q, mannose-binding lectin, C4d, Bb, C3, C3a, C5a and soluble C5b-9 were detected by enzyme-linked immunosorbent assay in 222 patients with active biopsy-proven lupus nephritis, 34 patients with lupus nephritis at remission, 82 patients with active systemic lupus erythematosus without renal involvement and 39 normal controls. The correlations between levels of complement components and clinicopathological features of these patients were further analyzed. ResultsPlasma levels of C1q and C3 significantly decreased, and the levels of Bb, C3a, C5a and soluble C5b-9 were significantly elevated in patients with active lupus nephritis compared with those in remission, active systemic lupus erythematosus without renal involvement group and normal controls. In the lupus nephritis group, soluble C5b-9 levels were inversely correlated with C1q and C4d levels (r = −0.412, P < 0.001 and r = −0.221, P = 0.002, respectively), but more strongly correlated with the level of Bb (r = 0.546, P < 0.001). C3b, Bb and C5b-9 could colocalize on glomeruli in lupus nephritis. Plasma Bb level was significantly correlated with some renal disease activity indices and was a risk factor for renal outcomes (hazard ratio = 1.745; 95% CI: 1.106-2.754; P = 0.017) in the lupus nephritis group. ConclusionsOur findings suggested that the activation of the complement alternative pathway might play a more important role in the pathogenesis of lupus nephritis, and factor Bb might be a useful marker for evaluating renal disease activity and outcomes.

Serum Vascular Endothelial Growth Factor (VEGF) as a Biomarker for Disease Activity in Lupus Nephritis.

Previous studies have shown that serum VEGF levels were elevated in patients with active systemic lupus erythematosus (SLE), especially in those with lupus nephritis (LN). In this case control study, we aimed to compare serum levels of VEGF in SLE patients between LN, non-LN and healthy participants to determine the association between serum VEGF levels and the activity and histological classes of lupus nephritis. Blood samples were obtained from 92 SLE patients (46 LN and 46 non-LN) and 26 controls. Data were collected from medical records. Serum VEGF assays were performed by specific, enzyme-linked immunosorbent assay kits (ELISA). Laboratory investigations included urinalysis, urine protein-creatinine ratio, serum creatinine, albumin and VEGF levels. Blood pressure, renal biopsy result and treatment were recorded. LN activity was evaluated using the renal subscale of the British Isles Lupus Assessment Group (rBILAG, 2004). The rBILAG measures blood pressure (diastolic and systolic), urine protein, serum creatinine, calculated glomerular filtration rate (GFR), presence of active urinary sediments and histological evidence of active nephritis. Serum VEGF was elevated in SLE patients with LN compared with the non-LN group and healthy controls. The levels found were significantly higher in the sera of patients with active nephritis compared to those with quiescent nephritis (P = 0.024). The study did not find a statistically significant relationship between serum VEGF levels and histological classes of LN. There was no significant difference of serum VEGF level between LN and non-LN SLE groups and between the non-LN group and healthy controls. However, there were increased levels of serum VEGF in the LN group, especially in patients with active nephritis as compared to quiescent nephritis group. This reflects the role of VEGF in the pathogenesis of lupus nephritis, however the clinical potential of this biomarker needs further study.

Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with systemic lupus erythematosus: a possible relation to proliferative nephritis

Introduction Angiotensin-converting enzyme (ACE) is crucial in the pathogenesis of systemic lupus erythematosus through angiotensin II which regulates vascular tone and endothelial functions. Objectives To study the frequency of ACE insertion/deletion (I/D) gene polymorphism in Egyptian children with systemic lupus erythematosus and its possible relation to the renal pathology in cases with lupus nephritis. Subjects and methods The frequency of ACE gene insertion/deletion polymorphism genotypes was determined in 78 Egyptian children with systemic lupus erythematosus and compared to a matched group of 140 healthy controls using polymerase chain reaction. Results The DD genotype of the ACE gene was higher in systemic lupus erythematosus patients when compared to controls ( P<0.0001; odds ratio (OR) 2.4; 95% confidence interval (CI) 1.7-3.3) and the D allele was more frequent than the I allele in systemic lupus erythematosus patients in comparison to controls ( P < 0.0001; OR = 2.2; 95% CI = (1.6-3.1). In the lupus nephritis group, the DD genotype was significantly higher in those with proliferative lupus nephritis when compared to those with non-proliferative lupus nephritis ( P = 0.02; OR = 1.45; 95% CI = 1.4-1.6). Also, patients with proliferative lupus nephritis showed a higher frequency of the D allele ( P < 0.001; OR = 1.98; 95% CI = 1.3-2.9). Conclusion The D allele and DD genotype of the ACE gene appear to be a risk factor for the susceptibility of systemic lupus erythematosus and occurrence of proliferative nephritis in Egyptian children.

Epithelial-mesenchymal transition in pediatric nephropathies

IntroductionEpithelial-mesenchymal transition (EMT) is a process in which epithelial cells may express mesenchymal cell markers with subsequent change in their functions, and it may be part of the etiopathogenesis of kidney disease. ObjectiveThe aim of this study was to evaluate the immunexpression of some EMT inducers and markers in frequent nephropathies in pediatric patients. Methods59 patients aged 2–18 years old were selected and divided into 6 groups of frequent nephropathies in children and adolescents, as well as one control group. Urea and creatinine data of the patients were recorded. TGF-β3, fibronectin, α-SMA and vimentin were evaluated by immunohistochemistry. ResultsGlomerular TGF-β3 was higher in the Lupus Nephritis and Acute Diffuse Glomerulonephritis (ADGN) groups than in the control group. Glomerular fibronectin was higher in the Podocytopathy, Lupus Nephritis, ADGN and Membranous Glomerulopathy patients than in control subjects. The expression of α-SMA was higher in the tubulointerstitial compartment of ADGN and Membranous Glomerulopathy groups than in the control group. Glomerular α-SMA was higher in ADGN patients than in control and Berger’s Disease groups. Glomerular vimentin was higher in individuals with ADGN than in those with Podocytopathy, Lupus Nephritis, Berger’s Disease and Thin Basement Membrane Disease/Alport Syndrome. There was a positive correlation between fibronectin in the tubulointerstitial compartment and creatinine levels, between α-SMA and vimentin in both tubulointerstitial and glomerular compartments, and between urea and creatinine levels of patients, regardless of their nephropathy (p<0.05 for all results). ConclusionThese markers may possibly be used as indicators of renal functional impairment in various nephropathies in pediatric patients.

Pregnancy Outcomes in Chinese Patients with Systemic Lupus Erythematosus (SLE): A Retrospective Study of 109 Pregnancies.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that primarily affects women during their reproductive years. The interaction between SLE and pregnancy remains debated. The objective of this study was to analyze the fetal and maternal outcomes of Chinese women with SLE. A total of 109 pregnancies in 83 SLE patients from June 2004 to June 2014 at a tertiary university hospital were reviewed retrospectively. Patients’ characteristics, clinical and laboratory data during pregnancy were obtained from electronic medical records. After exclusion of elective abortions, the live birth rate was 61.5%. Significantly, APS (antiphospholipid syndrome), disease activity, hypertension, hypocomplementemia, thrombocytopenia, and anemia during pregnancy were more commonly observed in fetal loss pregnancies than in live birth pregnancies. Compared to the 64 women with a history of SLE, 19 women with new-onset lupus during pregnancy had worse pregnancy outcome. Furthermore, the 64 patients with a history of SLE were divided into lupus nephritis group and SLE group (non-renal involvement). We found that the lupus nephritis group had worse maternal outcome than the SLE group. We conclude that new-onset lupus during pregnancy predicts both adverse maternal and fetal outcomes, while a history of lupus nephritis predicts adverse maternal outcomes. It is essential to provide SLE women with progestational counseling and regular multispecialty care during pregnancy.

CD4(+)CD25(+)CD127(-) and CD4(+)CD25(+)Foxp3(+) Regulatory T Cell Subsets in Mediating Autoimmune Reactivity in Systemic Lupus Erythematosus Patients.

The available clinical as well as experimental studies implicate participation of T regulatory (Treg) subsets in the pathogenesis and course of systemic lupus erythematosus (SLE). Introduction of the CD4+CD25+CD127− and CD4+CD25+Foxp3+ regulatory subpopulations analysis into immunological processes assessment and disease activation prognosis in patients with lupus nephritis (LN) may improve monitoring of disease activity and enable an early, and thus more effective, therapeutic treatment. The main goal of the study was to investigate whether the quantitative changes of Treg subpopulations are related to the clinical status of patients with LN. Fifty-four adult SLE patients divided into two groups according to their SLEDAI and renal SLEDAI scores were enrolled into the study. Subpopulations of CD4+CD25+CD127− and CD4+CD25+Foxp3+ phenotypes were determined by flow cytometry. The control group had higher absolute number of CD4+CD25+Foxp3+ cells compared with the study group (p < 0.001). Also, significant inverse correlation in the absolute number of CD4+CD25+Foxp3+ cells and SLEDAI score was observed. There were significant differences in the percentage and absolute number of CD4+CD25+Foxp3+ lymphocytes between active and non-active LN groups. The study group had statistically lower values of CD4+CD25+CD127− cells, both in the percentage (p < 0.001) as well as their absolute number (p = 0.014) compared to the control group. There were also statistically significant positive correlations between the absolute number of CD4+CD25+CD127− and CD4+CD25+Foxp3+ Tregs. In conclusion: (1) reduction in the number of regulatory CD4+CD25+Foxp3+ cells is a promising indicator of the activity of SLE, particularly of renal involvement; (2) determination of the number of regulatory cells using the CD4+CD25+CD127− phenotype is unreliable in patients with SLE.

Increased Granulocyte Heparanase Activity in Neutrophils from Patients with Lupus Nephritis and Idiopathic Membranous Nephropathy

Heparanase is a β-glucuronidase that cleaves sugar chains of heparan sulfate proteoglycans. It is believed that heparanase may be involved in the pathogenesis of proteinuria. The aim of this study was to assess the significance of heparanase in the pathogenesis of particular glomerulonephritis types. The evaluation of heparanase activity in serum, urine, and granulocytes and superoxide dismutase (SOD) activity in granulocytes of patients with lupus nephritis (n = 17), membranous nephropathy (n = 11), IgA nephropathy (n = 12), focal and segmental glomerulosclerosis (n = 18), mesangiocapillary glomerulonephritis (n = 12) and in 19 healthy volunteers were performed. The heparanase activity in granulocytes of patients with lupus nephritis and membranous nephropathy was higher than heparanase activity in granulocytes in the control group (p = 0.02 in both cases). This is the first observation of this phenomenon. There was no difference between SOD activity in granulocytes of patients with all assessed types of glomerulonephritis and the control group. A positive correlation between heparanase activity in urine and double-strain DNA antibodies (r = 0.51; p = 0.04), and reverse correlations between heparanase in urine and hemolytic activity of the complement (r = −0.57; p = 0.03) in the lupus nephritis group, and between heparanase activity in granulocytes and serum total protein level (r = −0.69; p = 0.02) in membranous nephropathy were observed. Increase in heparanase activity without changes in superoxide dismutase activity in the granulocytes from patients with lupus nephritis and membranous nephropathy was observed. It may be used as one of the markers of these disease activities.

Is there a role for urinary podocyte excretion assessment in lupus nephritis?

Objective To establish the occurrence and intensity of podocyturia and its relation to grade of disease activity, as defined by clinical and laboratory criteria. Methods Prospective, cross-sectional study involving 50 patients with lupus nephritis and 29 controls, which had podocyturia levels determined from random urine samples using an immunofluorescence technique. Disease activity was graded by BILAG (renal criteria) and an additional system used in the service (S2). Results Fifty patients with lupus nephritis (WHO classes III, IV and V), with a median age of 37 years, were evaluated. Of these, 86.5% were female, and 52% were BILAG A. Podocyturia quantification in the lupus nephritis and control groups differed significantly (p = 0.009). This score was higher in relation to classes III, IV and V. The correlation with C3 consumption was stronger (p = 0.011) than with C4. The highest levels were found in the most active groups (A and B of BILAG and S2). Lower podocyturia correlated with a lower dose of prednisone. There was no association with the intensity of proteinuria, hematuria or pyuria, serum creatinine levels, among others. Conclusions Podocyturia assessment, which was performed by immunofluorescence in this study, can be used as an indicator of disease activity with the advantage of being a urinary biomarker. The levels proved to be higher in patients with lupus nephritis than in the controls and were particularly higher in class IV.

Association of Serum CXCL13 with Intrarenal Ectopic Lymphoid Tissue Formation in Lupus Nephritis.

Aims. To assess the concentrations of serum CXCL13 and intrarenal ectopic lymphoid tissue (ELT) profiles and their correlation in the patients with lupus nephritis (LN). Methods. Serum CXCL13 levels were measured using enzyme-linked immunosorbent assays (ELISA). The expression of CD3, CD20, and CD21 in renal biopsy specimens was tested using immunohistochemical methods. Results. Serum CXCL13 levels were significantly higher in the LN group than those in the SLE group without LN and also in the type III and IV LN patients than in type V LN patients. LN patients with positive CD20 expression (CD20+ LN) had a longer disease course and poorer response to combination therapy and higher serum CXCL13 levels than CD20− LN patients. Moreover, the serum CXCL13 level was positively correlated with the number of B cells/HP in the renal tissue of LN patients. The coexpression patterns of CD3, CD20, and CD21 in the renal tissue of LN patients with different WHO pathological types were significantly different. Serum CXCL13 levels were significantly higher in ELT-2 type LN patients than in 0 or 1 type LN patients. Conclusions. This study suggested that increased serum levels of CXCL13 might be involved in renal ELT formation and renal impairment process in LN.

Analysis of interleukin 19 serum levels and single nucleotide polymorphisms in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease that affects multiple organs and diminishes a patients' quality of life. It has been suggested that interleukin 19 (IL-19) is engaged in intercellular signal transduction, which is related to the immune response and the local inflammatory reaction. Single nucleotide polymorphisms (SNPs) have been used to explore the genetic basis underlying the pathogenesis of SLE. In this study, we investigated the potential correlation between the functional IL19 SNP rs2243188 and SLE. The frequency of allele C in rs2243188 was lower in the SLE population, particularly when the dominant inheritance model was applied. There was also a significant difference in the allele C frequency between the lupus nephritis (LN) and non-LN groups in both the dominant and recessive inheritance models. In addition, we identified significant differences in the serum IL-19 levels between the different classes of SLE. Although this study is still at the preliminary stage, the correlations between the IL19 SNP and SLE, and between the IL-19 levels and the different subclasses of SLE provide a reference for further exploration.

Use of cyclophosphamide and other immunosuppressive drugs in the treatment of patients with lupus nephritis.

Systemic lupus erythematosus (SLE) is a chronic relapsing systemic autoimmune disease; one of the most serious complications is renal involvement, which is occurring in almost 50% of all patients at the beginning of the disease. The aim of the present study was to compare renal function, proteinuria, activity markers and treatment regimen of active and inactive SLE patients with renal involvement. We analyzed the correlation of serum blood urea nitrogen, creatinine level, glomerular filtration rate, urine total protein/serum creatinine (uTP/creat), CRP to classic activity markers of SLE (serum complement 3, -4 level, anti-dsDNA antibody). Moreover we analyzed the treatment modalities of patients with lupus nephritis (LN). Data of 418 SLE patients were analyzed, out of these patients 128 had biopsy proven lupus nephritis or had more than 3 + proteinuria by urine dipstick analysis (30% of all cases). Data of 128 patients with lupus nephritis were analyzed (mean age 32.18 +/- 11.48 year, time between the diagnosis of SLE and LN was 2.78 +/- 4.59 year). 48% of patients had diffuse proliferative glomerulonephritis, 75% of them received cyclic cyclophosphamide treatment. UTp (total protein)/creatinine level was significantly higher in active LN group (p = 0.03), and correlated to erythrocyte sedimentation rate (p = 0.002, R = 0.52). Mean anti-dsDNA level of patients with active LN was significantly higher (p < 0.001). Patients with active lupus nephritis are at higher risk of developing renal failure, activity markers and urine protein are elevated in these patients as compared to inactive patients, early aggressive immunosuppressive treatment needs to be started to prevent end-stage renal failure.

Evaluating the association of interleukin-10 gene promoter -592 A/C polymorphism with lupus nephritis susceptibility

BackgroundInterleukin-10 (IL-10) is an important immunoregulatory cytokine. There are few studies evaluating the association between IL-10 and lupus nephritis (LN). The aim of this study was to evaluate the association of IL-10 gene promoter -592 A/C with LN susceptibility. MethodsThe study was conducted on 84 patients with systemic lupus erythematosus (SLE). Patients were divided into LN group (Group I, 48 patients) and non-LN group (Group II, 36 patients). The -592 A/C polymorphisms in IL-10 promoter gene were determined by polymerase chain reaction and restriction fragment length polymorphism in both groups. IL-10 was determined by enzyme-linked immunosorbent assay. Frequencies of the genotypes were compared between LN and non-LN patients and among LN patients with different pathologic classes. ResultsThere was a significant increase in serum level of IL-10 (P = 0.001) in Group I compared with Group II and significant positive correlation between serum IL-10 and SLE disease activity index (r = 0.466, P = 0.001) in Group I. There were no significant differences in the distribution of the IL-10 gene promoter -592 A/C genotypes or the allele frequencies between Groups I and II. There was no significant difference between AC/CC and AA genotypes with SLE disease activity index, proteinuria, hematuria, anti-double-stranded DNA, and IL-10 in Group I. There was no significant difference in the distribution of AC and CC genotypes among different pathologic LN classes. ConclusionIL-10 suggested to play a role in pathogenesis and development of LN. However, the promoter -592 A/C of IL-10 gene suggested to be not associated with serum IL-10 levels or LN susceptibility. In addition, it appears that promoter -592 A/C of IL-10 gene not associated with LN activity or the pathologic classes of LN.