Systemic Lupus Erythematosus Nephritis Patients Research Articles

Neutrophils-derived Parameters as Cost-effective Inflammatory, Disease Activity Marker in Systemic Lupus Erythematosus (SLE) and Role in Prediction of Lupus Nephritis

Introduction: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease with various clinical manifestations and approximately 50% of the SLE patients develop lupus nephritis (LN), which increases the risk of renal failure, cardiovascular diseases and overall survival. Objectives: Evaluation of neutrophil-derived parameters (Neut-X, Neut-Y and Neut-Z) as an inflammatory, disease activity marker and as a predictor of nephritis in SLE patients. Material and Methods: In this cross-sectional study, 3 ml K3EDTA blood was taken from 110 SLE patients presented in Department of Clinical Immunology to evaluate neutrophil-derived parameters in Sysmex XT2000i haematology analyser and their correlation with other inflammatory biomarkers like, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) as well as SLE disease activity index-2000 (SLEDAI-2K). 24-hours urine protein levels were also estimated as a marker of renal involvement. Records of renal biopsy were available in 73 SLE patients, who belonged to different morphologic classification of LN. Results: After performing bivariate Spearman correlation analysis (SPSS software, version 26.0), Neut-X (measures cytoplasmic granularity by side scattering) and Neut-Z (vector sum of Neut-X and Neut-Y) showed a significant positive correlation ( r > 0.200, P < .05) with ESR, CRP and SLEDAI-2K while Neut-Y (measures nucleic acid content by sideward fluorescence) showed a significant negative correlation ( r > 0.200, P < .05) with ESR and CRP. Receiver-operating characteristic curve analysis was used to evaluate diagnostic value of 24-hour urine protein and predictive values of neutrophil-derived parameters for renal involvement in SLE patients. Among neutrophil-derived parameters, Neut-X was found to be the best predictor of renal dysfunction with highest AUC of 0.710 (95% CI: 0.604-0.816; cut-off: 1344.50; sensitivity: 84.7%; specificity: 50%) followed by Neut-Z with AUC of 0.707 (95% CI: 0.600-0.813; cut-off: 1403.67; sensitivity: 87.5%; specificity: 50%). Conclusion: Our study shows that neutrophil-derived parameters may be used as novel cost-effective, non-invasive biomarker of disease activity as well as for predicting renal involvement in SLE patients.

Systemic lupus erythematosus nephritis and COVID-19 disease.

Of the more than 20 studies published on SLE patients with COVID-19, none of the studies focused on lupus nephritis. We report the outcomes of renal biopsy-proven systemic lupus erythematosus (SLE) nephritis patients after COVID-19 disease. Our institute has been declared as a state COVID-19 hospital in the last week of March 2020. From then till now, we have admitted and managed COVID-19 patients from several districts of Andhra Pradesh and neighbouring states. We collected the data of patients with SLE nephritis contemporaneously from admission to the outcomes on a computerised proforma. We had identified sixteen patients with SLE nephritis who were admitted with COVID-19 disease. Of them, fourteen were females and two were males. The mean age was 29.3 years. Out of sixteen patients, seven required a mechanical ventilator and dialysis and eventually succumbed. One more patient died due to disseminated tuberculosis. Our results suggested that with an approximately 50% mortality rate, the COVID-19 disease had a calamitous effect on SLE nephritis patients. Key Points • We identified the significant risk factors for mortality: younger age, higher serum creatinine at presentation, higher CT severity score and lower serum albumin. • After the analysis done for this article, we decided to reduce the medications for SLE nephritis to prednisolone 10 mg/day when COVID-19 disease is contracted.

Inflammation-based biomarkers for the prediction of nephritis in systemic lupus erythematosus

Background/Aim: Inflammation is a crucial component in the pathophysiology of systemic lupus erythematosus (SLE) nephritis. Immune-based scores, such as the neutrophil-lymphocyte and the platelet-lymphocyte ratios (NLR and PLR, respectively) have been suggested as predictors of inflammation and prognosis in SLE. This study aimed to investigate the value of the systemic immune-inflammation index (SII), inflammatory prognostic index (IPI), and systemic inflammatory response index (SIRI) in SLE and lupus nephritis (LN). Methods: This case-control study consisted of 108 newly diagnosed SLE patients (separated into two subgroups, which included 34 patients with biopsy-proven LN and 74 without nephritis) and 108 age- and gender-matched healthy controls who presented to our outpatient clinic between October 2015 and June 2020. Patients with malignancy, lymphoproliferative and hematologic disorders, active infection, and autoimmune diseases other than SLE were excluded. Inflammation-based biomarkers were calculated at the first presentation of the disease and before any medication was administered. SII was calculated as Neutrophil/Lymphocyte x Platelet, SIRI as Neutrophil x Monocyte/Lymphocyte, and IPI as CRP x NLR/serum albumin. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) was used to measure disease activity. The capability of SII, SIRI, NLR, PLR, and IPI to distinguish between SLE patients with or without nephritis was assessed using receiver operating characteristic (ROC) curves. Correlations of inflammation-based scores (SII, SIRI, IPI, NLR) with disease activity and laboratory data of SLE patients were analyzed. Results: SII, SIRI, and IPI were significantly higher in SLE patients than in healthy controls (P=0.003, P=0.019, and P<0.001, respectively) and also significantly higher in patients with nephritis than in those without (P<0.001, P=0.009, and P=0.007, respectively). The area under the curve (AUC) for SII, SIRI, and IPI in terms of differentiating SLE patients with or without nephritis was 0.748, 0.690, and 0.663, respectively. The cut-off value of SII, SIRI, and IPI to predict LN was 552.25 (sensitivity: 64.7%; specificity: 64.9%; P<0.001), 1.08 (sensitivity: 61.8%; specificity: 62.2%; P=0.002), and 4.48 (sensitivity: 61.8%; specificity, 62.2%; P=0.007), respectively. Conclusion: SII, SIRI, and IPI may be valuable and promising inflammation-based biomarkers in SLE and for the presence of nephritis in SLE patients. SII was found to be the most reliable predictor of SLE among the inflammation-based biomarkers in our study.

Autoantibody-mediated impairment of DNASE1L3 activity in sporadic systemic lupus erythematosus.

Antibodies to double-stranded DNA (dsDNA) are prevalent in systemic lupus erythematosus (SLE), particularly in patients with lupus nephritis, yet the nature and regulation of antigenic cell-free DNA (cfDNA) are poorly understood. Null mutations in the secreted DNase DNASE1L3 cause human monogenic SLE with anti-dsDNA autoreactivity. We report that >50% of sporadic SLE patients with nephritis manifested reduced DNASE1L3 activity in circulation, which was associated with neutralizing autoantibodies to DNASE1L3. These patients had normal total plasma cfDNA levels but showed accumulation of cfDNA in circulating microparticles. Microparticle-associated cfDNA contained a higher fraction of longer polynucleosomal cfDNA fragments, which bound autoantibodies with higher affinity than mononucleosomal fragments. Autoantibodies to DNASE1L3-sensitive antigens on microparticles were prevalent in SLE nephritis patients and correlated with the accumulation of cfDNA in microparticles and with disease severity. DNASE1L3-sensitive antigens included DNA-associated proteins such as HMGB1. Our results reveal autoantibody-mediated impairment of DNASE1L3 activity as a common nongenetic mechanism facilitating anti-dsDNA autoreactivity in patients with severe sporadic SLE.

Thrombotic microangiopathy versus class IV lupus nephritis in systemic lupus erythematosus.

Kidney involvement is common in patients with systemic lupus erythematosus (SLE). This study investigates the clinical and prognostic characteristics of thrombotic microangiopathy (TMA) compared to class IV lupus nephritis in SLE patients. A retrospective review of patients who underwent kidney biopsy, with a primary diagnosis of SLE and TMA between June 2006 and September 2018 was conducted. Those patients were subsequently compared to patients with class IV lupus nephritis between January 2018 and December 2018. Demographics, laboratory, and serological data at the time of biopsy were abstracted. Among 214 SLE patients records screened, 27 were included in the final analysis. Eight patients had lupus-related TMA without evidence of active lupus nephritis, while 19 patients had class IV lupus nephritis without evidence of TMA. TMA patients had significantly higher lactate dehydrogenase levels (718 ± 499 vs. 264 ± 107.7 U/L, p = 0.009), serum C3 (100.6 ± 39.3 vs. 65.8 ± 27mg/dL, p = 0.049), white blood cell count (14743.8 ± 7933.3 vs. 5807.9 ± 2053.2 × 10E3/uL, p < 0.001), and total bilirubin (0.8 ± 0.5 vs. 0.3 ± 0.1mg/dL, p = 0.007) in addition to significantly lower platelet counts (158.4 ± 88.6 vs. 240.3 ± 100.3 × 10E3/uL, p = 0.03), and haptoglobin (68.8 ± 116.1 vs. 166.8 ± 95.4mg/dL, p = 0.03). After a median follow-up time of 53 weeks, 3 patients with TMA were dialysis-dependent (37.5%), compared with none in class IV lupus nephritis patients (p = 0.002). TMA-associated SLE has worse prognosis compared to class IV lupus nephritis. An array of laboratory and pathological findings may be of value in discriminating between those two entities.

P0414URINARY HEPCIDIN AS A BIOMARKER OF NEPHRITIS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS

Abstract Background and Aims Lupus nephritis (LN) is a common complication of systemic lupus erythematosus (SLE) that is associated with poor prognosis. The current available urinary biomarkers are neither sensitive nor specific for diagnosing LN. This study was undertaken to investigate whether urinary hepcidin represents a marker of nephritis in SLE patients. Method A cross-sectional study was conducted with 3 study groups compromising 30 patients with biopsy proven LN, 30 patients with non-nephritis SLE and 20 healthy control. Spot urinary samples were collected from all participants and the levels of hepcidin in urine were measured by ELISA, 24 h urinary proteins, urinary and serum creatinine were measured. Results Urinary hepcidin was significantly higher in LN patients than in non-nephritis SLE and control (470, 258, 43.0 ng/mg creatinine respectively) (P &amp;lt; 0.001) as shown in figure 1. Urinary hepcidin was significantly correlated with serum creatinine (P 0.017) and 24 hours urinary proteins (P 0.003). ROC curve cut-off values of urinary hepcidin were 4.3000, Area under curve (AUC) of hepcidin was 0.553, with sensitivity (SN) of 63.3%, specificity (SP) of 60%, Positive predictive value (PPV) 70.4, negative predictive value (NPV) 52.2 in SLE patients as shown in table 1 and figure 2. Conclusion Although urinary hepcidin level was significantly higher in LN patients than in non-nephritis SLE and control, it failed to discriminate patients with LN from those without. Further studies are still needed before considering urinary hepcidin as a non-invasive diagnostic marker of LN.

Resistivity Index (RI): A Fast and Reliable Indicator of Lupus Nephritis Severity

Abstract Background: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by production of pathogenic autoantibodies against nuclear structures. Lupus nephritis (LN) affects up to 60% of patients with SLE who develop immune complex-mediated renal injury and its squeal. Color Coded Doppler Ultrasound (CCDUS) allows non-invasive method for investigating renal hemodynamics. Renal resistive index (RI) measured using CCDUS reflects intrarenal vascular resistance. RI is an essential parameter in renal Doppler US and integrates arterial compliance, pulsatility and peripheral resistance. Aim of Study: Evaluate the role of Color-Coded Doppler Ultrasound in the assessment of nephritis in SLE patients and correlation between resistivity index (RI) and lupus nephritis pathological classes. Such assessment will help reaching diagnosis, guide the choice of management and monitor the follow-up. Patients and Methods: This study was conducted on ninety six SLE patients with renal affection, diagnosed clinically and laboratory first, then each patient included in the study was subjected to Ultrasound Doppler renal examination and renal biopsy. Twenty subjects with normal renal laboratory, ultrasound and Doppler findings were recruited as a control group. B-Mode ultrasound and Color-coded Doppler exami-nation were performed using GE Logiq p5 Ultrasound machine by (3.5-5MHz) transducer. Doppler parameters were adjusted before Doppler examination scan. First general renal vascu-larity was checked then RI was calculated in different segments of intra renal arteries at upper, mild and lower poles. RI=(peak systolic velocity-end diastolic velocity)/peak systolic velocity. The normal value is » 0.60 with 0.70 being around the upper limits of normal. Finally, radiological findings were correlated with clinical findings and correlated with biopsy results. Results: The study included 96 SLE patients, their ages ranged from (13-45) mean 28.19±8.026. Males represented 12.5% (12 patients) and females represented 87.5% (84 patients). Renal biopsy showed 70 patients (73%) with LN and 26 patients (27%) with no renal affection.The parenchymal echogenicity was increased in all LN seventy patients except one (1.5%). 15 patients (21.5%) scored grade I echogenicity while 16 patients (22.9%) scored grade II and 38 patients (54.1%) scored grade III. There was a significant increase in renal RI in lupus nephritis LN patients, p-value 0.022. Distribution of renal pathologic classes within the LN group. Class II (7 patients) represented 10%, class III (27 patients) represented 38.5%, class IV (22 patients) represented 31,5% and class, V (11 patients) represented 15.7% and class IV (3 patients) repre-sented 4.3 % of LN patients according to biopsy results. There was positive correlation between RI and renal biopsy classi-fication with high significance, p-value 0.001 with r=0.794. Conclusion: There is a significant correlation between pathologic RI and lupus nephritis histological classes suggest-ing a role for RI as a severity marker.

SAT-411 Anti nuclear Antibody negative Lupus like Nephritis. A 5 case series report

Systemic lupus erythematosus (SLE) is a disease due to an autoantibody response to nuclear and cytoplasmic antigen which is associated with the inflammatory cascades and end-organ damage in multiple organs like kidney, skin, brain, etc. In the kidney, immune-complex deposits leads to the deterioration of renal function leading to a condition called lupus nephritis. Lupus nephritis is a common but serious complication in SLE patients. Previously, American College of Rheumatology (ACR) required at least 4 of 11 clinical or laboratory criteria to diagnose SLE which included malar rash, discoid rash, photosensitivity, oral ulcers, nonerosive arthritis, pleuritis or pericarditis, kidney disorder, neurological disorder, hematologic disorder and positive antinuclear antibody. In 2019, there has been an update in this criteria, where positive antinuclear antibody is given as entry level criterion. If negative, cases cannot be classified as Systemic lupus erythematosus. If positive, further accumulation of 10 points is required for diagnosis of SLE. Lupus-like glomerulonephritis is defined as immune complex kidney disease with full house pattern in glomeruli where immunofluorescence staining for immunoglobulin G (IgG), IgA, IgM, complement (C3), and C1q are positive in an ANA negative patients. This findings is otherwise described as diagnostic criteria for lupus nephritis in SLE patients. Extraglomerular immune deposits within tubular basement membranes and tubuloreticular inclusions are other characteristic features that can be found in lupus nephritis. A total of 5 cases of ANA negative lupus like nephritis were reported in the department of renal pathology in University of Alberta between 1st January 2019 to 30th September, 2019. All of our cases were positive (IgG, IgA, IgM, C3, C1q) in immunofluorescence and were described as full house pattern. In light microscopy, 2 of the cases correlated with stage IV lupus nephritis, 2 correlated with stage V lupus nephritis and 1 case correlated with stage I lupus nephritis. Tubuloreticular inclusions were present in the one of the case. All patients responded to prednisolone as suggested by follow up laboratory datas.Table 1Variations in parameters among five cases.Case 1Case 2Case 3Case 4Case 5Age/sex62y/f56y/f24y/m42y/m7y/fANANegativeNegativeNegativeNegativeNegativedsDNANegative (positive after 2 month borderline 127 <120MFU)NegativeNegativeNegativeNegativeProtein creatinine ratio (PCR)306.3553.9(Normal <13.0 mg/mmol)238.57439.33975.52Urine Hemoglobin2+1+3+1+1+Serum. Creatinine121 (40-100 µmol/L)84 (40-100 µmol/L)106 (50-120 µmol/L)146 (50-120 µmol/L)29 (20-75 µmol/L)HematologyNormalNormalNormalNormalNormalLupus Nephritis gradeIVIIVVV Open table in a new tab In ANA negative patients, immune complex mediated glomerulonephritis with full house immunofluorescence pattern may be considered as lupus like glomerulonephritis. Other features like tubuloreticular inclusions, DsDNA might be positive in these patients. These patients present and response to treatment like renal limited lupus nephritis. They may develop full blown SLE in long term; hence close follow up is required. However, other causes of immune complex mediated glomerulonephritis must be ruled out before considering this diagnosis.

Anti-α-enolase antibody combined with β2 microglobulin evaluated the incidence of nephritis in systemic lupus erythematosus patients.

Anti-α-enolase antibody (Ab) combined with β2 microglobulin (β2-MG) were investigated to predict the incidence of nephritis in systemic lupus erythematosus (SLE) patients. Levels of serum anti-α-enolase Ab and urinary β2-MG were detected in 115 SLE patients, 29 SLE patients with nephritis and 70 healthy controls by ELISA and immunoturbidimetry, respectively. Furthermore, the correlation between anti-α-enolase Ab combined with β2-MG and the incidence of nephritis in SLE patients was evaluated by correlation analysis. The optical density value of serum anti-α-enolase Ab in SLE patients with nephritis (0.84) was greatly increased compared with SLE patients (0.76) or healthy controls (0.54). Moreover, the levels of urinary β2-MG in SLE patients with nephritis (6.75 mg/L) were increased compared with SLE patients (3.45 mg/L) or healthy controls (1.48 mg/L). There was a positive correlation between the level of anti-α-enolase Ab and β2-MG ( r = 0.754). Furthermore, anti-α-enolase Ab combined with β2-MG for evaluating the incidence of nephritis in SLE patients had the best assessment of the effectiveness (area under the receiver operating characteristic curve (AUC): 92.7%) compared with only anti-α-enolase Ab (AUC: 80.9%) or β2-MG (AUC: 84.5%). These data suggested that anti-α-enolase Ab may be a potential indicator for the prediction of nephritis in SLE patients.

Urinary neutrophil gelatinase-associated lipocalin and monocyte chemoattractant protein 1 as biomarkers for lupus nephritis in Colombian SLE patients.

Background Information regarding urinary biomarkers in Mestizo and Afro-Latin-American patients is very limited. We investigated whether levels of urinary neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant protein 1 (MCP-1) are good biomarkers to differentiate patients with lupus nephritis among Latin-American systemic lupus erythematosus (SLE) patients. Methods SLE patients meeting the revised American College of Rheumatology classification criteria for SLE were recruited. Urinary levels of NGAL and MCP-1 were measured using a commercial ELISA kit. Serum anti-C1q antibodies were measured by ELISA. SLE activity was measured with the systemic lupus erythematosus disease activity index (SLEDAI). Mann-Whitney tests were used to compare data and Spearman's rank correlations were used to examine associations between continuous variables. In addition, receiver operating characteristic curves were performed. Results One hundred and twenty SLE patients were recruited (87% women) with a median age of 32.8 ± 12.1 years and median disease duration of 7.3 ± 6.9 years. Afro-Latin-Americans had a significantly higher prevalence of lupus nephritis and higher SLEDAI scores than Mestizos. The three biomarkers were significantly higher in patients with lupus nephritis than in patients without lupus nephritis. In addition, urinary NGAL and MCP-1 were significantly higher in patients with active lupus nephritis than in inactive lupus nephritis. Urinary NGAL levels were significantly higher in Afro-Latin-American patients. A receiver operating characteristic curve for urinary biomarkers for lupus nephritis in all SLE patients showed a good level of sensitivity and specificity. Conclusion In our cohort of SLE patients, we found that urinary NGAL and MCP-1 in addition to anti-C1q antibodies were useful biomarkers for the identification of renal involvement and discrimination of active lupus nephritis among patients with renal disease.

Association between the Presence of Autoantibodies Targeting Ficolin-3 and Active Nephritis in Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of multiple autoantibodies. Antibodies against Ficolin-3 were previously identified in the sera of some SLE patients, but their prevalence and significance have not been yet investigated. The aims of this study were to determine the prevalence of anti-ficolin-3 antibodies among SLE patients and to investigate their potential as diagnostic and/or prognostic biomarkers in SLE. In this retrospective study, sera from SLE patients (n = 165) were selected from a preexisting declared biological collection. Samples from healthy controls (n = 48) were matched with SLE sera. Disease activity was determined according to the SLEDAI score. Anti-ficolin-3, anti-dsDNA and anti-C1q antibodies levels were measured in sera by ELISA. First, a highly significant difference was found in the anti-ficolin-3 levels between SLE patients and healthy subjects. Anti-ficolin-3 antibodies were detected as positive in 56 of 165 (34%) SLE patients. The titer of anti-ficolin-3 antibodies was correlated with the SLEDAI score (r = 0.38, p<0.0001). The presence of anti-ficolin-3 antibodies was associated with anti-C1q and anti-dsDNA antibodies. Regarding associations with clinical manifestations, the presence of active lupus nephritis was significantly associated with the presence of anti-ficolin-3 antibodies (p≤0.001). This association with renal involvement was higher with anti-ficolin-3 or anti-C1q antibodies than with other auto-antibodies. Interestingly, the combination of anti-ficolin-3 and anti-C1q antibodies demonstrated higher specificity than any other serological biomarker. These results suggest that anti-ficolin-3 antibodies could be useful for the diagnosis of active nephritis in SLE patients.

IgA Nephropathy in a Patient with Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disorder. One of the most typical aspects of SLE is renal involvement. Lupus nephritis is a serious disease whose prognosis can usually be improved dramatically by treatment. The occurrence of non-lupus nephritis in SLE patients has rarely been reported. IgA Nephropathy (IgAN) and lupus nephritis (LN) have quite different laboratory, histopathologic findings and extra-renal clinical manifestations. In the light of these data we thought that IgAN and LN have different pathogeneses. We report a patient with SLE in whom IgA nephropathy was diagnosed.

Rare Case of Lupus Nephritis With Negative Antinuclear Antibodies, Double-Stranded DNA Antibodies and Positive Anti-Ro/SSA Antibodies

Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease that is characterized by various antibodies to nuclear and cytoplasmic antigens and diagnosed by either fulfilling the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria, American College of Rheumatology (ACR) criteria or by Renal Biopsy. Renal involvement is common in SLE and is primarily related to anti-double-stranded DNA antibodies. However, small group of SLE nephritis patients have shown negative anti-dsDNA and ANA. We present a case of 25-year-old female who presented with proteinuria and negative serum antibodies except anti-Ro/SSA. Renal biopsy was performed and was consistent with class IV lupus nephritis (LN). In this report, we highlight the possible role of anti-Ro antibodies in the pathogenesis and the prognosis of LN, although the mechanism is yet to be understood. Anti-Ro/SSA antibodies might play an important role in the pathogenesis and prognosis in LN. However, further studies are required to understand the exact mechanism. World J Nephrol Urol. 2016;5(2):48-49 doi: http://dx.doi.org/10.14740/wjnu272e

Function of the Th17/interleukin-17A immune response in murine lupus nephritis.

The CD4+ T cell immune response plays a pivotal role in the immunopathogenesis of human and experimental lupus nephritis, but the contribution of the Th17/interleukin-17 (IL-17) immune pathway to renal tissue injury in systemic lupus erythematosus (SLE) remains to be elucidated. The aim of this study was to characterize the function of the Th17/IL-17A immune response in 2 murine models of lupus nephritis. IL-17A-deficient MRL/MPJ-Fas(lpr) /2J (MRL/lpr) mice were generated, and the clinical course of nephritis was monitored by assessing the levels of albuminuria, extent of renal tissue injury, and functional parameters. In addition, lupus-prone (NZB × NZW)F1 (NZB/NZW) mice were treated with anti-IL-17A and anti-interferon-γ (anti-IFNγ) antibodies, and their effects on the clinical course of lupus nephritis were assessed. Characterization of renal IL-17A-producing and IFNγ-producing T cells in MRL/lpr and NZB/NZW mice revealed low numbers of infiltrating CD3+IL-17A+ cells. Renal IL-17A was mainly produced by CD4/CD8 double-negative CD3+ T cells and CD4+ Th17 cells. In contrast, the number of renal CD3+IFNγ+ cells continuously increased over time and largely consisted of typical CD4+ Th1 cells. IL-17A deficiency did not affect the morphologic or functional parameters in MRL/lpr mice with lupus nephritis, nor did IL-17A neutralization affect the clinical course of nephritis in NZB/NZW mice, but anti-IFNγ treatment attenuated the severity of the disease. The Th17/IL-17A immune response plays no major role in the immunopathogenesis of lupus nephritis in MRL/lpr and NZB/NZW mice. Thus, the results of this study do not support the hypothesis that IL-17A targeting could be an intriguing new therapeutic approach for the management of proliferative lupus nephritis in SLE patients.

Th-17 related regulatory network in the pathogenesis of Arab patients with systemic lupus erythematosus and lupus nephritis.

The present study aimed to identify the genes involved in the pathogenesis of systemic lupus erythematosus (SLE) in Arabs by investigating a panel of 84 genes related to the t helper (Th)17-related regulatory network and to further explore the expression levels of serum interleukin (IL)-17A and IL-17F in a studied cohort. A comparative analysis of gene expression profile in SLE and lupus nephritis (LN) patients against that of healthy controls (HC) was performed. A quantitative real-time polymerase chain reaction (PCR) (Th17 autoimmunity and inflammation) array analysis was performed in peripheral white blood cells of 66 SLE patients under specific medical treatment and 30 age/gender/ethnically matched healthy controls. Statistical analysis was carried out using the RT(2) Profiler TM PCR Data Analysis tool. The analysis of Th17 pathway revealed 14 genes (IL-17A, IL-17C, IL-17D, IL-17F, IL-18, IL-12RB2, IL-23R, CCL2, CCL20, CXCL5, MMP3, RORC, STAT4 and TRAF6) that are differentially expressed in SLE and HC (fold change [FC]<2, P<0.0006). No significant difference in expression profiles was observed between SLE and LN. A significant difference in serum concentration of IL-17A (P=0.002) and IL-17F (P=0.002) was observed between SLE (13.91±4.25) and LN (18.26±4.24). Our study is the first to investigate a panel of 84 genes related to Th17 regulatory pathway in Arab SLE subjects and the first to explore the effect of current immunosuppression regimens on Th17 regulatory pathway. It paves the way for understanding the etiology of SLE and autoimmune diseases in general.

Familial Mediterranean fever gene (MEFV) mutations and disease severity in systemic lupus erythematosus (SLE): implications for the role of the E148Q MEFV allele in inflammation.

Observed low prevalence of SLE among familial Mediterranean fever (FMF) patients in several large cohorts suggests a possible protective effect of the MEFV mutations from SLE. In contrast, SLE patient carriers for the common MEFV mutations had rather complex disease expression with an increased frequency of febrile episodes and pleurisy and a decreased renal complication rate. Our aim was to investigate the prevalence of MEFV gene mutations in patients with SLE and their effect on organ involvement in a well-defined group of biopsy-proven SLE nephritis patients. The prevalence of four MEFV gene mutations (M694V, M680I, V726A and E148Q) was investigated in 114 SLE patients and effect on disease severity was analyzed in patients with biopsy-proven SLE nephritis. None of the SLE patients fulfilled the revised Tel-Hashomer criteria. Fourteen of 114 SLE patients (12.2%) were found to carry at least one MEFV mutation. A single patient in the SLE-Nephritis group was compound heterozygous for M694V/M680I mutations and only one patient in the SLE-Mild group was homozygous for E148Q mutation. Carrier frequency was similar to controls in SLE patients (12.2 vs 18.8%, p = 0.34). After the exclusion of the less penetrant E148Q mutation, re-analysis revealed an association between exon 10 mutations and SLE nephritis (p = 0.050, odds ratio (OR) = 4.16, 95% confidence interval (CI) = 1.04-16.6). Carrier rate for the E148Q mutation decreased in the SLE group (controls vs. SLE = 20/186 vs. 3/114, p = 0.08) and E148Q mutation was absent in SLE nephritis (controls vs. SLE nephritis = 20/186 vs. 0/47, p = 0.016, OR = 11.69, 95% CI = 0.69-197.13). Carrier rate for the studied MEFV mutations was slightly lower in the SLE group, which is in agreement with previous observations that FMF may confer some protection from SLE. Exon 10 mutations were associated with SLE nephritis after the exclusion of the E148Q mutation. The significance of the E148Q as a disease-causing mutation is controversial, and whether E148Q substitution is a polymorphism generally affecting inflammatory pathways is not addressed in the current literature. In this regard, absence of the E148Q mutation in SLE nephritis may serve as a clue for further investigation into its role as a general modulatory polymorphism for inflammation. This clarification is necessary to conclude whether other more penetrant MEFV gene mutations confer susceptibility to nephritis in SLE.

SIL7R concentrations in the serum reflect disease activity in the lupus kidney

ObjectivesEvaluation of disease activity in systemic lupus erythematosus (SLE) nephritis is a challenge, and repeated renal biopsies are usually needed in order to confirm a suspicion of flare. In a...

THU0001 Association of Pneumococcal Vaccination with In-Hospital Mortality in Systemic Lupus Erythematosis Patients: A Nationwide Study

BackgroundThe 23-valent capsular polysaccharide pneumococcal vaccine, Pneumovax, protects against invasive pneumococcal pneumonia and is indicated for patients with chronic autoimmune diseases and/or on chronic immunosuppressive treatment. The effect of polysaccharide...

MBL2 gene variants coding for mannose-binding lectin deficiency are associated with increased risk of nephritis in Danish patients with systemic lupus erythematosus.

Autoimmunity may in part result from deficiencies in the processing of apoptotic debris. As mannose-binding lectin (MBL) is involved in such processes, we hypothesized that the variants in the MBL2 gene resulting in MBL deficiency confer an increased risk of nephritis in systemic lupus erythematosus (SLE). A total of 171 SLE patients attending a Danish tertiary rheumatology referral center were included. Common variant alleles in exon 1 of the MBL2 gene (R52C, rs5030737; G54D, rs1800450; G57E, rs1800451) were genotyped. The normal allele and variant alleles are termed A and O, respectively. The follow-up period was defined as the time from fulfillment of the ACR 1987 classification criteria for SLE until the occurrence of an event (nephritis, end-stage renal disease (ESRD), or death) or end of follow-up. Cox regression analyses were controlled for gender, age and race. During a median follow-up of 5.7 years, nephritis developed in 94 patients, and ESRD developed in 16 of these patients. Twenty-seven patients died. The distribution of the MBL2 genotypes A/A, A/O and O/O was 58%, 35% and 7.0%, respectively. Compared to the rest, O/O patients had 2.6 times (95% CI: 1.2-5.5) higher risk of developing nephritis, and their risk of death after 10 years was 6.0 times increased (95% CI: 1.0-36). MBL serum levels below 100 ng/ml were associated with a 2.0 (95% CI: 1.2-3.4; p = 0.007) increased risk of developing nephritis. ESRD and histological class of nephritis were not associated with MBL deficiency. Genetically determined MBL deficiency was associated with development of nephritis in SLE patients, but not with histological class of nephritis or ESRD.

Immunoglobulin G anti-endothelial cell antibodies: inducers of endothelial cell apoptosis in pulmonary arterial hypertension?

Endothelial cell (EC) apoptosis seems to play an important role in the pathophysiology of pulmonary arterial hypertension (PAH). We aimed to test the hypothesis that circulating anti-endothelial cell antibodies (AECA) of PAH patients induce EC apoptosis. Immunoglobulin (Ig)G was purified from sera of PAH patients (n = 26), patients with systemic lupus erythematosus (SLE) nephritis without PAH (n = 16), patients with systemic sclerosis (SSc) without PAH (n = 58) and healthy controls (n = 14). Human umbilical vein endothelial cells (HUVECs) were incubated with patient or healthy control IgG for 24 h. Thereafter, apoptosis was quantified by annexin A5 binding and hypoploid cell enumeration by flow cytometry. Furthermore, real-time cell electronic sensing (RT-CES™) technology was used to monitor the effects of purified IgG from patient and healthy control IgG on HUVECs. As demonstrated previously, IgG of AECA-positive SLE nephritis patients (n = 7) induced a higher percentage of apoptosis of HUVECs compared to IgG of AECA-negative SLE nephritis patients and healthy controls. Furthermore, IgG of AECA-positive SLE nephritis patients induced a marked decrease in cell index as assessed by RT-CES™ technology. IgG of AECA-positive PAH patients (n = 12) and SSc patients (n = 13) did not alter the percentage of HUVEC apoptosis or cell index compared to IgG of AECA-negative PAH and SSc patients and healthy controls. AECA-positive PAH patients, in contrast to SLE nephritis patients, do not have circulating IgG AECA that enhances apoptosis of HUVECs in vitro. Further studies should focus on other mechanisms by which AECA may enhance EC apoptosis in PAH, such as antibody-dependent cell-mediated cytotoxicity.