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.     

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

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

Sleep disturbance in female patients with systemic lupus erythematosus and its relation to disease parameters

Aim of the workTo assess the prevalence of sleep disturbance in female patients with systemic lupus erythematosus (SLE) and to evaluate the correlation between sleep disturbance and some disease parameters.Patients and MethodsThe Pittsburgh Sleep Quality Index (PSQI) was used to investigate the sleeping habits of 30 female patients with SLE and of 30 healthy age and sex-matched controls. Depressed mood was assessed using the Center for Epidemiological Studies Depression scale (CES-D), functional disability was assessed with the Health Assessment Questionnaire (HAQ) and pain severity was assessed using the visual analogue scale (VAS). Disease activity was measured using the SLE disease activity index (SLEDAI). Disease severity and cumulative damage were measured using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage (SLICC/ACR DI).ResultsThe mean global scores for the PSQI were significantly different between cases and controls (8.47 ± 3.53 versus 5.10 ± 3.66, p = 0.000) indicating poor sleep quality for these patients compared to healthy controls, and 76.7% (23 patients) were poor sleepers. Sleep disturbances were correlated with disease duration (p = 0.001), functional disability (p = 0.001), SLEDAI (p = 0.000), pain severity (p = 0.002), organ damage (p = 0.000) and depressed mood (p = 0.000). However, with multivariate linear regression analysis SLEDAI and SLICC/ACR were the only significant predictors associated with higher level of PSQI.ConclusionSleep disturbances are prevalent among female SLE patients, with multiple factors contributing to it, but disease activity and cumulative disease damage were the only predictors of sleep quality. Assessment and management of sleep disturbances should be part of the routine care of SLE patients.     

Lymphopenia and systemic lupus erythematosus,a preliminary study: Correlation with clinical manifestations,disease activity and damage indices

IntroductionSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by excessive autoantibody production against ‘self’ antigens and immunocomplex formation, resulting in frequent widespread inflammatory damage to target multiple organ systems.Aim of workTo determine the association of lymphopenia with the clinical manifestations, serologic abnormalities, disease activity and disease damage as well as drug intake in SLE patients.Patients and methodsThe present study was carried out on forty-five SLE female patients fulfilling the American College of Rheumatology (ACR) revised criteria for the diagnosis of SLE. They were divided into two groups according to the lymphocytes’ count: Group-I: thirty patients with lymphopenia (<1500/mm³) and group-II: fifteen patients without lymphopenia (⩾1500/mm³). Ten healthy age matched females (group-III) taken as a control group. Patients and control groups were recruited from the Rheumatology and Rehabilitation Department, Faculty of Medicine, Cairo University Hospitals. Disease activity was assessed using the SLE Disease Activity Index (SLEDAI). Disease damage was assessed with Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index.ResultsLymphopenia in patients with SLE was found to be associated with lupus nephritis (p = 0.023), leucopenia (p = 0.004), increased disease activity index (p = 0.03) and increased organ damage index (p = 0.02), and was not associated with other clinical lupus manifestations, serological abnormalities or with the drug intake (p > 0.05).ConclusionLymphopenia in SLE was associated with lupus nephritis, leucopenia and increased both disease activity and organ damage indices.     

Interleukin-27 and its relation to disease parameters in SLE patients

IntroductionIL-27 exerts profound anti-inflammatory effects in several experimental autoimmune models, suggesting that it may be therapeutically relevant in SLE.Aim of the workTo evaluate IL-27 level in SLE patients and its association to clinical manifestations, disease activity parameters and management strategy.Patients and methodsWe studied 80 SLE patients and 50 controls in a cross sectional study. Demographic, clinical and serological data were evaluated. Systemic lupus erythematosus disease activity index (SLEDAI) and Systemic Lupus International Collaboration Clinics/ACR damage index (SLICC) were assessed. Serum IL-27 was measured by ELISA.ResultsThere was statistically significant difference in IL-27 level in SLE patients and healthy controls (9.7 ± 21.9 pg/ml vs 20.2 ± 47.3 pg/ml in SLE vs controls, respectively) (p = 0.04), also it was found that IL-27 level was statistically significantly lower in SLE patients with lupus nephritis (p = 0.02) and cerebritis (p = 0.03). Interleukin 27 level had a statistically significant negative correlation with the cumulative dose of hydroxychloroquine and azathioprine (r = ?0.3, p = 0.03 and r = ?0.3 and p = 0.04, respectively).ConclusionIL-27 has anti-inflammatory effect in SLE patients especially those without nephritis or cerebritis and can be therapeutically relevant in SLE. To confirm our results we propose larger scale, multicentre studies with longer evaluation periods.     

Serum BLyS and APRIL as possible indicators of disease activity in pediatric systemic lupus erythematosus and juvenile idiopathic arthritis

Aim of the workTo assess serum levels of B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL) to determine their correlations with disease activity in pediatric systemic lupus erythematosus (pSLE) and juvenile idiopathic arthritis (JIA) patients.Patients and methodsTwenty-nine pSLE patients and 33 JIA patients were recruited. SLE disease activity was assessed using the systemic lupus erythematosus disease activity index (SLEDAI), while the juvenile arthritis 27 joint disease activity score (JADAS-27) was calculated for JIA patients. Serum samples were assayed for BLyS and APRIL by the enzyme linked immunosorbent assay (ELISA).ResultsSerum BLyS and APRIL were elevated in both pSLE and JIA patients compared to controls. Serum BLyS levels correlated with both SLE and JIA disease activity (p = 0.042, p = 0.019, respectively) whereas serum APRIL levels correlated positively with JADAS-27 and inversely with SLEDAI (p = 0.001, p = 0.02, respectively). Elevated serum BLyS and APRIL were significantly associated with a lower incidence of nephritis (p = 0.043, p = 0.016, respectively), while elevated serum APRIL significantly associated with negative anti-dsDNA in pSLE patients (p = 0.017). In JIA patients, both serum BLyS and APRIL were significantly associated with the presence of ANA (p = 0.008, p < 0.001, respectively), while high serum APRIL associated with the presence of RF (p = 0.035). APRIL and BLYS levels correlated with each other positively in JIA but inversely in pSLE patients.ConclusionSerum BLyS showed elevated levels that correlated significantly with pSLE and JIA disease activity, accordingly anti-BLyS therapy might be of great benefit to offset disease flare. The inverse correlations observed between APRIL with both BLyS and disease activity in pSLE patients raises the possibility of being a down regulator of the disease process.     

Auditory disorders in patients with systemic lupus erythematosus: Relation to clinical parameters

Aim of the workTo evaluate the hearing disorders in SLE patients with particular regard to their frequency and relationship to disease duration and activity.Patients and methodsTwenty female SLE patients were enrolled in the study. Assessment of disease activity was done using the SLE disease activity index (SLEDAI). Another 20 otologically healthy subjects of matched age and sex served as controls. Auditory assessment was performed and included otoscopic examination, pure tone audiometry (PTA), acoustic immittance testing and speech audiometry.ResultsThe PTA was abnormal in 13 (65%) patients; 4 had tinnitus and 1 vertigo. The PTA results showed a highly significant statistical difference from the control (p < 0.001). Otoscopic examination, acoustic immittance testing and speech audiometry of all patients were normal. A significant difference was found in the age at disease onset between those with and without abnormal PTA (p = 0.023). Moreover, there was a significantly lower hearing level (right ear) at 12,000 Hz in juvenile-onset (N = 6) (20.83 ± 3.76 db) compared to adult-onset cases (32.5 ± 15.66 db) (p = 0.02). No significant difference was present in the audiovestibular manifestations (p = 0.114), clinical, laboratory parameters or disease activity between those with or without hearing loss. However, hearing levels were significantly lower in those with lupus nephritis and those receiving hydroxychloroquine.ConclusionPure tone audiometry revealed SNHL in 65% of SLE patients. Absence of audiovestibular manifestations does not exclude inner ear affection. Age at disease onset is remarkably associated with hearing loss in SLE. Lupus nephritis and hydroxychloroquine use are associated with lower hearing levels and possible early hearing loss.     

IL-17 in cutaneous lupus erythematosus

BackgroundLupus erythematosus (LE) is a heterogeneous disease with broad clinical spectrum from cutaneous to visceral and systemic inflammation. IL-17 isoforms (IL-17A and IL-17F) are proinflammatory cytokines with unclear implications in lupus erythematosus pathogenesis. In this study we focused upon IL-17 in normal and modified lupus skin with a correlative study between local and serological expression.Material and methods89 subjects were recruited and divided in 5 groups—10 patients with psoriasis (disease control group), 13 healthy controls, 26 with discoid chronic lupus (DLE), 23 with systemic lupus erythematosus (SLE) and 17 with subacute lupus erythematosus (SCLE). Blood samples and skin punched-biopsy specimens were performed. Serum IL-17A, IL-17F, and IL-23 concentrations were determined by ELISA. Skin IL-17A and CD4 expression were evaluated by immunohistochemistry.ResultsImmunohistochemical expression of IL-17A was higher in DLE, SCLE and SLE patients than in negative control subjects (all p < 0.05). Serum IL-17A concentrations were higher in DLE and SLE patients than in negative controls (p < 0.05). Serum IL-17A levels were similar in SCLE and negative controls (p > 0.05). Serum IL-17F concentrations were higher in DLE, SCLE and SLE patients than in healthy controls (all p < 0.05). In DLE, SCLE, SLE patients and healthy controls we observed comparable levels of IL-23 (p > 0.05). Serum anti Ro antibodies correlate with IL-17A+ lymphocytes from SCLE lesion and SLE normal skin (all p < 0.05).ConclusionIL-17 isoforms (IL-17A and IL-17F) are implicated in SLE but also in DLE and SCLE immunopathogenesis.     

Transferrina y ceruloplasmina en orina de pacientes con lupus eritematoso sistémico. ¿Son útiles para diferenciar pacientes con nefritis lúpica?

Background and objectiveDiagnosis of lupus nephritis (LN) is usually based on renal biopsy, which is an invasive technique that involves multiple risks. Therefore, different biomarkers have emerged as alternatives for the diagnosis of LN. Nonetheless, studies regarding urinary biomarkers in Latin American patients are limited. The objective of this study was to assess the diagnostic value of urinary transferrin and ceruloplasmin to differentiate patients who have renal involvement from those who do not.Materials and methodsSystemic lupus erythematosus (SLE) patients that met the revised American College of Rheumatology (ACR) classification criteria were recruited. Patients with another autoimmune disease, active infection (urinary tract or systemic infection), renal replacement therapy, human immunodeficiency virus infection or pregnancy were excluded. A urine sample was collected from each patient. LN was diagnosed according to ACR criteria. The activity and chronicity of LN were measured using the Austin indices. Urinary transferrin and ceruloplasmin levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Mann-Whitney U test and Student's t-test were used to compare data. Spearman's rank correlation was used to determine associations. Lastly, receiver operating characteristic (ROC) curves were created.ResultsThe study involved 120 SLE patients. In all, 85% were female, 76% mestizo, the mean age was 32.8 ± 12.1 years and mean systemic lupus erythematosus disease activity index (SLEDAI) was 8.4 ± 8.9; 64% had renal involvement. Urinary levels of the two biomarkers were significantly higher in patients with LN compared to those without LN. Similarly, urinary levels of both biomarkers were significantly higher in patients with active LN compared to those with inactive LN. Furthermore, urinary transferrin levels were significantly higher in Afro-Latin American patients. On the other hand, urinary transferrin levels correlated with SLEDAI and proteinuria, and transferrin and ceruloplasmin levels correlated with each other. The diagnostic value of ROC curves for these urinary biomarkers for LN were good.ConclusionsIn our cohort of SLE patients, we found that transferrin and ceruloplasmin were potential biomarkers for LN, and can even differentiate active LN.     

Mannose binding lectin 2 promotor-221 X/Y gene polymorphism in Egyptian systemic lupus erythematosus patients

Aim of the workThe present study was undertaken to determine whether mannose binding lectin-2 (MBL2) promotor-221X/Y gene polymorphism had a possible association with systemic lupus erythematosus (SLE) in Mansoura city.Patients and methodsWe analyzed functional polymorphisms in the promoter of MBL2 gene in 106 Egyptian SLE patients and 99 healthy controls by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). SLE disease activity was evaluated using SLE Disease Activity Index (SLEDAI) and organ damage was evaluated using SLE International Collaborating Clinic Damage Index (SLICC/DI).ResultsThe patients were 95 females and 11 males with a mean age of 34.4 ± 10.2 years and disease duration of 4 ± 3.03 years. Genotype frequencies of MBL2 were significantly different between patients and controls. The YY genotype was significantly associated with SLE in 77 (72.6%) patients compared to the control in 59 (59.6%) (p = 0.048). The XY genotype was in 29 (27.4%) patients and in 40 (40.4%) control. An association was found between the XY genotype and alopecia (p = 0.048), central nervous system involvement (p = 0.03), vasculitis (p = 0.004) and anti-phospholipid syndrome (p = 0.001) while the YY genotype was associated with discoid rash, low serum complement level (C3; p = 0.014 and C4; p = 0.008) and with the presence of anticardiolipin antibodies (p = 0.032). MBL genotype did not show any correlation with SLEDAI or SLICC/DI.ConclusionOur results indicate that MBL2 promotor-221X/Y polymorphism is a possible key-player for SLE development as well as the occurrence of some clinical and laboratory features. Further longitudinal studies including other single nucleoproteins are needed to clarify the role of MBL2.     

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.     

IL-17 is a key cytokine correlating with disease activity and clinical presentation of systemic lupus erythematosus

AimsTo determine the role of IL-17 cytokine in systemic lupus erythematosus (SLE) patients and its association with clinical presentation of the disease and disease activity.Methods72 SLE patients and 70 healthy age and sex matched controls were included in the study. SLE disease activity was assessed in all patients with SLE disease activity index (SLEDAI-2K) scores. Plasma levels of IL-6, and IL-17 were measured by enzyme-linked immunosorbent assay and correlated their levels with clinical manifestations of the disease and SLEDAI-2K.ResultsPlasma levels of IL-6 and IL-17 were significantly elevated in SLE patients than in control subjects (13.98 ± 6.95 versus 7.47 ± 1.23 pg/mL) and (19.47 ± 10.21 versus 9.93 ± 1.89 pg/mL), respectively. IL-6 and IL-17 were positively correlated with SLEDAI-2K scores (r = 0.684 at P < 0.001, r = 0.322 at P = 0.006), and lupus nephritis (r = 0.364 at P = 0.002, r = 0.474 at P < 0.001) respectively; similarly, the IL-17/IL-6 ratio was positively correlated with SLEDAI-2K (r = 0.243 at P = 0.039). Also, the level of both cytokines was positively correlated to each other during periods of disease activity (r = 0.755, P < 0.001) as well as during remission (r = 0.384, P = 0.040).ConclusionOver-expression of IL-17 correlates with disease activity of SLE. A longitudinal study in a larger cohort of SLE patients can help validate the results.     

Expression of T helper 17 cells and interleukin 17 in lupus nephritis patients

Background

Modern data suggest that interleukin 17 (Il-17) and Il-17 producing cells play an important role in the pathogenesis of lupus nephritis (LN). It was reported that T helper 17 migrate to the kidney and contribute to inflammatory processes.

Association between anti-Ro 60 kDa (SS-A) autoantibodies and hypocomplementemia in systemic lupus erythematosus patients from Algiers prefectures

BackgroundSystemic lupus erythematosus (SLE) is characterized by a vicious cycle maintaining systemic inflammation. It starts by autoantibody production, immune complex formation and complement activation that contribute to inflammation, tissue damage and further autoantibody production.Aim of the workTo evaluate the association between the auto-antibodies (abs), circulating immune complexes (CIC), and complement activity in SLE patients.Patients and methodsThis study involved 30 female SLE patients analyzed for autoantibodies, complement profile including complement hemolytic 50 (CH50), alternative pathway 50_, factor B, C1q, C2, C3 and C4 as well as C1q-CIC. SLE disease activity was assessed by the SLE Disease Activity Index (SLEDAI).ResultsThe age of patients was 34 ± 12.8 years, disease duration was 5.2 ± 3.2 years and their mean SLEDAI was 9.96 ± 4.2. Anti-SSA, anti-dsDNA, anti-C1q abs, and CIC were detected in 36.7%, 50%, 50% and 30% of patients, respectively. Anti-SSA were higher in patients with lower compared to normal CH₅₀ activity and C3 level (24.7 vs 88.6 U/ml; p = 0.002 and 118.6 ± 25.18 U/ml vs 15.9 ± 7.3; p < 0.0001 respectively) than the other autoantibodies. Increased CIC were higher in patients with lupus nephritis and were associated with anti-SSA, anti-SSB, anti-C1q, anti-Sm and in patients with low CH50 activity. The CIC significantly correlated with anti-C1q (r = 0.69, p < 0.0001), anti-SSA (r = 0.5, p = 0.005) and negatively with CH₅₀ (r = −0.4, p = 0.046).ConclusionsThe current study confirms that the etiopathogenic anti-SSA autoantibodies are the most associated with hypocomplementemia in SLE. This would stimulate future researches for validation of predictive biomarkers earlier than hypocomplementemia which is still the major unmet need in lupus research and patient care.     

Metabolic syndrome in patients with systemic lupus erythematosus from South India

ObjectivesTo find the prevalence of metabolic syndrome in systemic lupus erythematosus (SLE) compared to controls and to identify association of metabolic syndrome with SLE disease activity and damage.MethodsA total of 82 SLE and 82 healthy controls were studied. Metabolic syndrome was defined by National Cholesterol Education Program-Adult Treatment Panel III (NCEP ATP III), consensus definition for Asian Indian Adults and World Health Organisation (WHO) 1999 definition, and associations with lupus characteristics, disease activity, and damage were examined. Insulin resistance (IR) was estimated using the homeostasis model assessment for IR (HOMA-IR).ResultsMetabolic syndrome was present in 24.39% SLE and 12.19% controls (p < 0.04) by NCEP ATP III criteria; 29.26% SLE and 19.51% controls (p = 0.14) by consensus definition for Asian Indians; 18.2% SLE and 7.31% controls (p < 0.035) by WHO 1999 criteria.Hypertension and hypertriglyceridemia were more frequent in SLE than in controls. Mean body mass index, diastolic and systolic blood pressure, triglycerides, and total cholesterol were higher in SLE than in controls. HOMA-IR (median, range) was 1.31 (0.06–9.32) and 1.55 (0.01–7.92), p = 0.09 in SLE and controls, respectively. There was no association of metabolic syndrome with disease activity/damage and prednisolone use. SLE patients with metabolic syndrome had a significantly longer duration of disease compared to patients without metabolic syndrome.ConclusionSouth Indian SLE patients have higher prevalence of NCEP ATP III and WHO defined metabolic syndrome compared to healthy controls. SLE patients have an altered lipid profile, but there was no IR and no association of metabolic syndrome with disease activity or damage.     

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.     

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.     

Does anti-DNA positivity increase the incidence of secondary antiphospholipid syndrome in lupus patients?

Aim of the workTo detect the incidence of secondary antiphospholipid syndrome (APS) among Systemic lupus erythematosus (SLE) patients with positive anti-DNA antibodies.Patients and methodsWe studied 342 SLE patients; Group I: anti-DNA positive SLE patients (n = 208) and Group II: anti-DNA negative SLE patients (n = 134), with a female to male ratio of 9.39:1 and a mean age of 27.49 ± 7.94 years and disease duration of 5.74 ± 3.97 years. Full history taking, thorough clinical examination, laboratory and relevant radiological investigations were performed. Disease activity was assessed using systemic lupus erythematosus disease activity index (SLEDAI). Anti-dsDNA tests were carried out by indirect Immunofluorescence (IF) technique. Anti cardiolipin antibodies (IgG and IgM) and Anti-β₂ glycoprotein-I antibody of IgG and/or IgM isotype were detected by ELISA.ResultsThe clinical manifestations, disease activity and laboratory investigations of the SLE patients varied according to the anti-DNA antibodies. Thirty-six patients (17.3%) had secondary APS in those with positive anti-DNA antibodies while only16 (11.9%) had secondary APS in those with negative anti-DNA antibodies, with no significant differences between both groups.ConclusionApparent higher incidence of secondary APS was detected in anti-DNA positive SLE patients. The non significant differences between both groups may suggest that anti-DNA positivity cannot be considered as the only predictor of secondary APS and further studies may be needed to detect other factors which may increase the incidence of APS in SLE patients.     

Cardiovascular events in patients with systemic lupus erythematosus

IntroductionCardiovascular involvement represents the leading cause of mortality in SLE patients. Its most common manifestations include pericarditis, valvular affections, conduction disorders, and arterial hypertension. Pulmonary hypertension and coronary arteritis are seen less often. Venous thrombosis directly related to SLE affects about 10% of SLE cases. Acceleration of atherosclerosis is very important and so are the ensuing cardiocerebral events, the most common of these being myocardial infarctions (MIs), cerebrovascular events, thromboembolic events (TEs), heart failure, and sudden death. We analyzed the frequency of cardiovascular events and their relationship to selected risk factors in a cohort of SLE patients followed in a single clinical center.MethodsThe studied population comprised 63 SLE patients (women: men = 53: 10, mean age 38.4 ± 12.7 years, mean disease duration 143 ± 82 months, BMI 24.74 ± 5.06, waist circumference 83.38 ± 16.58 cm), including 25 patients with lupus nephritis. Intima-media thickness (IMT) was assessed ultrasonographically in a standard manner. Of laboratory values, serum concentrations of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), anti-ds-DNA, antinucleosomal antibodies (ANUC), complement components C3 and C4, and ENA antibodies were measured. Clinical disease activity was assessed using indices of activity and cumulative damage such as SLEDAI and SLICC. Screening for traditional cardiovascular risk factors was based on appropriate questionnaires. Detailed analysis was employed to calculate cumulative doses of glucocorticoids and other immunosuppressants and to evaluate the use of anticoagulants, antiaggregants, statins, and ACE inhibitors.ResultsA total of 21 (33%) patients had a history of cardiovascular event during the course of their SLE: there were 3 myocardial infarctions (4.7% of the entire population, 14% of all cardiovascular events), 8 cerebrovascular events (12.7%, resp. 38%), and 12 thromboembolic events (19%, resp. 57%). In two patients, two different manifestations of cardiovascular involvement were combined – cerebrovascular event and MI in one, cerebrovascular event and TE event in the other. Cardiovascular events correlated with obesity, waist and hip circumference, smoking, total cholesterol, LDL, TC/HDL ratio, and apolipoproteins A-1 and B.Borderline statistical significance was noted for disease activity, hsCRP, positivity of RNP and anticardiolipin antibodies, lupus anticoagulant (p = 0.06) and intima-media thickness (p = 0.07). Subgroups of patients with cardiovascular event and arterial hypertension were also analyzed in more detail.ConclusionIn this article, we point to the high rate of cardiovascular events in SLE patients, thus confirming the need to pay appropriate attention to cardiovascular problems in the field of rheumatology.     

Prevalence and impact of chronic hepatitis C virus infection on the clinical manifestations and disease activity among patients suffering from systemic lupus erythematosus

Aim of the workTo study the prevalence of anti-HCV antibodies among patients suffering from systemic lupus erythematosus (SLE) as well as to determine the impact of chronic HCV infection on the clinical manifestations and disease activity.Patients and methodsNinety-eight consecutive SLE patients presented to the rheumatology department, Cairo University Hospitals were included in the study. All patients were screened for anti-HCV antibodies using a 3rd generation enzyme-linked immune-sorbent assay (ELISA). Patients with positive anti-HCV were tested for the presence of HCV-RNA by polymerase chain reaction (PCR). Patients were classified into two groups; HCV/SLE and non-HCV/SLE according to the presence or absence of anti-HCV antibodies.ResultsTwenty/98 patients (20.4%) were positive for HCV antibody. Eight/98 patients (8.2%) had active viremia. SLE patients with positive anti-HCV antibodies tend to be older in age and having a longer SLE duration than non-HCV/SLE Patients. HCV/SLE patients had significantly lower mucocutaneous manifestations (p < 0.05) and higher cardiac manifestations and fundus abnormalities (p < 0.04, p < 0.01 respectively) than non-HCV/SLE patients. There was no statistical difference between the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score between both groups. Patients with HCV/SLE were less frequently on oral steroids than patients with non-HCV/SLE.ConclusionHCV antibodies and active HCV viremia were found in 20.4% and 8.2% respectively among SLE patients. SLE with positive anti-HCV antibodies tend to be older in age and having longer SLE disease duration, lower mucocutaneous and higher cardiac manifestations and fundus abnormalities. Concomitant chronic HCV infection has no adverse impact on SLEDAI.