Levels In Systemic Lupus Erythematosus Patients Research Articles

The Impact of the IL-10 Gene Polymorphism on mRNA Expression and IL-10 Serum Concentration in Polish Lupus Patients.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies against a lot of nuclear components. Despite many studies on the genetic background of this disease, the pathogenesis remains unclear. The aim of the study is to comprehensively evaluate the polymorphism of the IL-10 promoter gene, its mRNA expression, and the serum IL-10 concentration of SLE female patients and females age-matched controls. Analyzing the association between the level of the tested cytokine and the polymorphism genotype-1082; -819; -592, we found statistically higher serum IL-10 levels in SLE patients compared to in healthy controls (11.9 ± 2.2 pg/mL vs. 9.4 ± 1.7 pg/mL, accordingly; p < 0.0001). We did not find statistically significant differences in the gene polymorphism of IL-10 among SLE patients and controls. The most significant observation derived from our study is that IL-10 mRNA transcripts are upregulated in SLE patients compared to in healthy controls (p < 0.0001). According to our results, the presence of the IL-10 genetic polymorphism has no clinical significance for the development of SLE, and subsequent differences in mRNA and IL-10 concentration results from the influence of other factors which should be the subject of further research.

Serum Uric Acid Combined with Homocysteine as a Predictive Biomarker of Lupus Nephritis.

Serum uric acid (UA) and homocysteine (Hcy) are potential biomarkers of systemic lupus erythematosus (SLE). In this study, the expressions of UA and Hcy in SLE patients and the predictive value of these two parameters for lupus nephritis (LN) were studied. A total of 476 SLE patients were recruited to this case-control study, of which 176 SLE patients diagnosed with LN and 300 without LN. Serum UA and Hcy levels were analyzed. Multivariate logistic regression analysis was used to evaluate the relationship between serum UA and Hcy and LN. The receiver operating characteristic (ROC) curves were used to predict the role of combination of serum UA and Hcy in LN. We found that serum UA and Hcy levels in SLE patients with LN were significantly higher than those in controls (p<0.05). Multivariate logistic regressions showed that serum UA (OR+=+1.003, 95+% CI: 1.001-1.006, p+=+0.003), apolipoprotein B (Apo B) (OR+=+21.361, 95+% CI: 2.312-195.373, p+=+0.007) and Hcy (OR+=+1.042, 95+% CI: 1.011-1.080, p+=+0.014) were independent markers of LN. Combined serum UA and Hcy revealed a better result (AUC+=+0.718, 95+% CI: 0.670-0.676, p<0.001) in prediction of LN compared to that of the serum UA (AUC+=+0.710) and Hcy (AUC+=+0.657) independently. In conclusion, serum UA and Hcy could be predictive biomarkers of LN, and joint detection of serum UA and Hcy might be useful in the clinical setting.

Environmental exposure to polycyclic aromatic hydrocarbons: An underestimated risk factor for systemic lupus erythematosus onset and progression

ObjectiveTo investigate the link between systemic lupus erythematosus (SLE) incidence and exposure to environmental polycyclic aromatic hydrocarbons (PAH). MethodsA case-control study (ChiCTR2000038187) involving 316 SLE patients and 851 healthy controls (HCs) was executed. Environmental exposure was assessed via a questionnaire, stratified by gender and age (females <35 and ≥35 years, males). Blood samples collected from 89 HCs, 85 inactive, and 95 active SLE patients were used to measure serum benzo[a]pyrene diol epoxide -albumin (BPDE-Alb) adducts and PAH concentrations, indicating long-term and short-term exposure respectively. Intergroup comparisons and statistical analyses were conducted using R version 4.3.1. ResultsDiverse patterns were found in how environmental factors affect SLE onset across different demographics. Lifestyle exposure factors were found to be a stronger determinant of SLE onset than occupational exposure factors in women under 35. Indoor air pollution had a significant impact on SLE incidence, potentially comparable to outdoor air pollution. Lifestyle-related PAH exposure had a greater impact on SLE than occupational PAH exposure. PAH exposure levels progressively increase from HCs to inactive and active SLE patients. Active SLE patients show markedly higher BPDE-Alb levels than HCs. ConclusionsEnvironmental PAH, particularly lifestyle-related, are significant, yet under-recognized, risk factors for SLE. Statement of environmental implicationWe examined the relationship between exposure to environmental polycyclic aromatic hydrocarbons (PAH) and the incidence of systemic lupus erythematosus (SLE). PAH, prevalent in sources such as cigarette smoke, air pollution, and charred food, pose significant health hazards. This study is the first to investigate specific PAH exposure levels in SLE patients. We determined actual PAH exposure levels in both SLE patients and healthy individuals and indicated that long-term PAH exposure biomarker is more reliable for evaluating exposure in non-occupationally exposed groups like SLE, compared to short-term markers. These findings provide valuable insights for future research on similar non-occupationally exposed populations.

Role of Advanced Glycation End Products as New Biomarkers in Systemic Lupus Erythematosus.

Advanced glycation end-products (AGEs) may play a relevant role as inducers in the chronic inflammatory pathway present in immune-mediated diseases, such as systemic lupus erythematosus (SLE). AGEs concentrations have been associated, with discrepant results to date, with some parameters such as disease activity or accrual damage, suggesting their potential usefulness as biomarkers of the disease. Our objectives are to confirm differences in AGEs levels measured by cutaneous autofluorescence between SLE patients and healthy controls (HC) and to study their correlation with various disease parameters. Cross-sectional study, where AGEs levels were measured by skin autofluorescence, and SLE patients' data were compared with those of sex- and age-matched HC in a 1:3 proportion through a multiple linear regression model. Associations of AGEs levels with demographic and clinical data were analyzed through ANOVA tests. Both analyses were adjusted for confounders. AGEs levels in SLE patients were significantly higher than in HC (p < 0.001). We found statistically significant positive associations with SLE disease activity index (SLEDAI) and damage index (SDI), physician and patient global assessment, C-reactive protein, leukocyturia, complement C4, IL-6 and oral ulcers. We also found a negative statistically significant association with current positivity of anti-nuclear and anti-Ro60 antibodies. AGEs seem to have a contribution in LES pathophysiology, being associated with activity and damage and having a role as a new management and prognosis biomarker in this disease. The association with specific antibodies and disease manifestations may indicate a specific clinical phenotype related to higher or lower AGEs levels.

علاقة الانترلوكينات 37 و40 مع داء الذئبة الحمامية الجهازية في نساء مرضى عراقيات

The primary cause of systemic lupus erythematosus (SLE) is autoantibodies to self-antigens. Interleukin 37 (IL-37) and Interleukin 40 (IL-40) are important cytokines which may play a role in regulating inflammation and involved in pathogenesis of autoimmune diseases like SLE. This study was aimed the interleukin levels (IL-37 and IL-40) during systemic lupus erythematous (SLE) development in Iraqi female patients. The present study was conducted on 100 female SLE patients and 100 healthy female controls, with mean ages of patients and controls )32.85 ± 0.99 and 32.05 ± 0.91)years, respectively. Erythrocytes Sedimentation Rate (ESR) and C-reactive protein (CRP) were investigated in this study. Enzyme-linked immune sorbent assay(ELISA) kits examined levels of interleukins in the serum of patients and healthy controls. The results found that IL-37 levels in SLE patients were lower than in controls(23.39 ±0.92ng/mL vs48.02 ±0.46ng/mL), respectively, with a statistically significant. While serum IL-40 levels appeared to have a higher significant in patients compared with the healthy control (9.98 ±0.32ng/mL vs4.16 ±0.05ng/mL) respectively. Also, ESR and CRP was high significant in patients compared with healthy controls. In conclusion, these findings suggest that IL-40 and IL-37 could be used as a biomarker for SLE.

Altered expression of miR-125a and dysregulated cytokines in systemic lupus erythematosus: Unveiling diagnostic and prognostic markers.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder impacting multiple organs, influenced by genetic factors, especially those related to the immune system. However, there is a need for new biomarkers in SLE. MicroRNA-125a (miR-125a) levels are decreased in T cells, B cells, and dendritic cells of SLE patients. MiR-125a plays a regulatory role in controlling the levels of tumor necrosis factor-alpha (TNF-α) and interleukin 12 (IL-12), which are crucial pro-inflammatory cytokines in SLE pathogenesis. To assess the levels of miR-125a, IL-12, and TNF-α in SLE patients' plasma, evaluating their diagnostic and prognostic value. The study included 100 healthy individuals, 50 newly diagnosed (ND), and 50 SLE patients undergoing treatment. The patients were monitored for a duration of 24 wk to observe and record instances of relapses. MiR-125a expression was measured using real-time reverse transcription polymerase chain reaction, while ELISA kits were used to assess IL-12 and TNF-α production. The results showed significantly reduced miR-125a expression in SLE patients compared to healthy individuals, with the lowest levels in ND patients. TNF-α and IL-12 expression levels were significantly elevated in SLE patients, especially in the early stages of the disease. Receiver operating characteristic curve analyses, and Cox-Mantel Log-rank tests indicated miR-125a, TNF-α, and IL-12 as proper diagnostic biomarkers for SLE. A negative correlation was found between plasma miR-125a expression and IL-12/TNF-α levels in SLE patients. Decreased miR-125a levels may be involved in the development of SLE, while elevated levels of IL-12 and TNF-α contribute to immune dysregulation. These findings offer new diagnostic and prognostic markers for SLE. Moreover, the negative correlation observed suggests an interaction between miR-125a, TNF-α, and IL-12. Further research is necessary to uncover the underlying mechanisms that govern these relationships.

Association of vitamin D level with systemic lupus erythematosus: A case-control study

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune connective tissue disease. SLE patients are more prone to vitamin D deficiency because of their light sensitivity, renal involvement, and prolonged steroid use. This current study aimed to determine the relationship between vitamin D deficiency and SLE. Methods: In this case-control study, 50 SLE patients (cases) and 50 healthy people (controls) were recruited. The reference value of vitamin D is as follows: normal ≥ 30 ng/ml, deficient ≤ 20 ng/ml, and insufficient 21–29 ng/ml. Results: The mean (standard deviation) of vitamin D levels in SLE patients was 19.5 (5.3) ng/mL, which was significantly lower than those in healthy controls, 27.3 (10.0) ng/mL (P&lt;0.001). The healthy controls had a higher proportion of people with normal vitamin D levels (≥ 30 ng/ml). We noticed a moderate negative correlation between vitamin D levels and fatigability, while a moderate positive correlation was seen with hemoglobin levels and the duration of sun exposure. However, in multiple logistic regression analysis, all the associations mentioned above disappeared. Conclusion: Although vitamin deficiency was found to be associated with SLE, its relationship disappears when the confounding by other variables is considered in the analysis.

Proteomic analysis of lysine 2-hydroxyisobutyryl in SLE reveals protein modification alteration in complement and coagulation cascades and platelet activation Pathways

BackgroundPost-translational modifications (PTMs) are considered to be an important factor in the pathogenesis of Systemic lupus erythematosus (SLE). Lysine 2-hydroxyisobutyryl (Khib), as an emerging post-translational modification of proteins, is involved in some important biological metabolic activities. However, there are poor studies on its correlation with diseases, especially SLE.ObjectiveWe performed quantitative, comparative, and bioinformatic analysis of Khib proteins in Peripheral blood mononuclear cells (PBMCs) of SLE patients and PBMCs of healthy controls. Searching for pathways related to SLE disease progression and exploring the role of Khib in SLE.MethodsKhib levels in SLE patients and healthy controls were compared based on liquid chromatography tandem mass spectrometry, then proteomic analysis was conducted.ResultsCompared with healthy controls, Khib in SLE patients was up-regulated at 865 sites of 416 proteins and down-regulated at 630 sites of 349 proteins. The site abundance, distribution and function of Khib protein were investigated further. Bioinformatics analysis showed that Complement and coagulation cascades and Platelet activation in immune-related pathways were significantly enriched, suggesting that differentially modified proteins among them may affect SLE.ConclusionKhib in PBMCs of SLE patients was significantly up- or down-regulated compared with healthy controls. Khib modification of key proteins in the Complement and coagulation cascades and Platelet activation pathways affects platelet activation and aggregation, coagulation functions in SLE patients. This result provides a new direction for the possible significance of Khib in the pathogenesis of SLE patients.

Association between endothelin-1 and systemic lupus erythematosus: insights from a case–control study

Systemic lupus erythematosus (SLE) is a chronic rheumatic disorder. Endothelin-1, a vasoconstrictor, belongs to the endothelin family and is associated with vascular-related damages. To date, association between ET-1 and pathogenesis of SLE remains unclear. This case–control study was carried out by 314 SLE, 252 non-SLE diseases patients and 500 healthy controls. Serum ET-1, CCN3, IL-28B levels were detected by ELISA, and ET-1 gene polymorphisms (rs5369, rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs4145451, rs6458155, rs9369217) were genotyped with Kompetitive Allele-Specific PCR. SLE patients had high levels of ET-1, which were correlated with some clinical, laboratory features. Serum CCN3, IL-28B levels were higher in SLE patients, and ET-1 levels were positively correlated with the two cytokines. Rs5370, rs1476046, rs2070699, rs2071942, rs2071943, rs3087459, rs6458155 and rs2070699 were associated with SLE risk. Rs2070699 (T, TT) was related to SLE patients with alopecia. Rs5370 (T, TT, TG), rs1476046 (G,GA), rs2071942 (G,GA) and rs2071943 (G,GA) were associated with SLE patients with pericarditis, pyuria and fever manifestation, respectively. Rs3087459 (CC) and rs9369217 (TC) were related to SLE patients with positive anti-SSB antibody. Rs5369 (AA) was associated with IgG and CRP levels in SLE patients. In conclusion, elevated serum ET-1 in SLE patients may be a potential disease marker, and its gene polymorphisms were related to SLE susceptibility.

Relationship between Disease Characteristics and Circulating Interleukin 6 in a Well-Characterized Cohort of Patients with Systemic Lupus Erythematosus.

Interleukin-6 (IL-6) is a proinflammatory cytokine that mediates pleiotropic functions in immune responses and inflammatory diseases. The literature lacks studies, with a clinical perspective, on the relationship between IL-6 serum levels and the characteristics of the disease in patients with systemic lupus erythematosus (SLE). In the present work, we aimed to analyze the association between circulating IL-6 and disease manifestations in a well-characterized series of patients with SLE. Serum IL-6 levels and disease activity (SLEDAI-2K), severity (Katz) and damage index (SLICC-DI), complete lipid profile, and subclinical carotid atherosclerosis were evaluated in 284 patients with SLE. In addition, a complete characterization of the complement system was performed in samples from patients with SLE. A multivariate linear regression analysis was carried out to study the relationship between clinical and laboratory characteristics of the disease and IL-6 levels. Age (beta coef. 0.07 [95%CI 0.01-0.1] pg/mL, p = 0.014), C-reactive protein (beta coef. 0.21 [95%CI 0.16-0.25] pg/mL, p < 0.01), and male gender (beta coef. 2 [95%CI 0.3-0.5] pg/mL, p = 0.024), were positively associated with higher IL-6 levels in SLE patients. Most disease characteristics and damage and activity indices did not show significant relationships with IL-6. However, after multivariate analysis, IL-6 was associated with lower serum levels of HDL cholesterol (beta coef. -0.04 [95%CI -0.08-(-0.1)] pg/mL, p = 0.011), and apolipoprotein A1 (beta coef. -0.02 [95%CI -0.04-(-0.001)] pg/mL, p = 0.035). In contrast, the alternative complement cascade, C1inh, and C3a were all positively and independently associated with higher serum levels of IL-6. Moreover, stratification of the Systematic Coronary Risk Assessment 2 (SCORE2) results according to different categories of cardiovascular risk was associated with higher circulating serum IL-6 levels (beta coef. 0.2 [95%CI 0.02-0.4], pg/mL, p = 0.028). In conclusion, in a large series of SLE patients, IL-6 was not associated with disease-related features of SLE, including damage, severity, or activity indices. However, an association was found between serum IL-6 levels and circulating C3a and cardiovascular risk. Our study emphasizes the importance that IL-6 could have in cardiovascular disease and complement system disruption of SLE patients. Therapies targeting IL-6 could have a role in these two clinical manifestations of patients with SLE.

Elevated Layilin-Positive Monocyte Levels in the Peripheral Blood of Patients with Systemic Lupus Erythematosus Reflect Their Autoimmune Status

ABSTRACT Objective To investigate the expression of layilin (LAYN) in human circulating monocytes and lymphocytes and its clinical significance in systemic lupus erythematosus (SLE). Methods Blood samples were collected from 51 SLE patients and 50 healthy controls. Flow cytometry was used to analyze LAYN in lymphocytes and monocyte subsets. Functionally characterized molecules including human HLA, CD74 and CD62L were studied in LAYN+ monocytes. A correlation analysis was conducted between LAYN-related subsets and clinical indicators of SLE such as anti-double-stranded DNA and complements levels. ROC curves were used to explore the potential clinical diagnostic value of LAYN in SLE. Results LAYN was significantly higher in monocytes than in lymphocytes and higher in CD14+CD16+ monocytes than in CD14-CD16+ and CD14+CD16- monocytes. CD74 was upregulated and CD62L was downregulated in LAYN+ monocytes compared with LAYN- monocytes. The absolute number of LAYN+ monocytes was increased in SLE patients, and the median fluorescence intensity of HLA was decreased. LAYN+ monocytes were positively correlated with complement C4, while decreased CD62L+ percentages in LAYN+ monocytes were negatively correlated with C4. The ROC analysis revealed that the area under the curve (AUCs) for CD62L+ percentages in LAYN+ monocytes, LAYN+ lymphocyte numbers, and LAYN+ monocyte numbers to distinguish SLE from healthy individuals were 0.6245, 0.6196 and 0.6173, respectively. Conclusion LAYN is differentially expressed in monocytes and their subpopulations and has corresponding functional differences. Changes in LAYN expression on monocytes are associated with complement C4 levels in SLE patients. These suggest that LAYN may be involved in the pathogenesis of SLE. Abbreviation ANOVA: analysis of variance; anti-dsDNA: anti-double-stranded DNA; anti-ENA: anti-extractable nuclear antigen; anti-SSA: anti-Sjogren syndrome A; anti-SSB: anti-Sjogren syndrome B; anti-U1RNP: anti-U1 ribonucleoprotein; AUC: area under the ROC curve; CBC: complete blood count; CD62L: L-selectin; CD74/Ii: MHC class II invariant chain; CD44/HCAM: homing cell adhesion molecule; cMos: classical monocytes; CRP: C-reactive protein; CXCR2: C-X-C motif chemokine receptor 2; CXCR4: C-X-C motif chemokine receptor 4; ESR: erythrocyte sedimentation rate; HCs: healthy controls; HA: hyaluronan; HLA: human leukocyte antigen; Ig: immunoglobulin; iMos: intermediate monocytes; LAYN: layilin; MFI: median fluorescence intensity; MIF: migration inhibitory factor; ncMos: nonclassical monocytes; PBMCs: peripheral blood mononuclear cells; ROC: receiver operating characteristic curve; SLE: systemic lupus erythematosus; SLEDAI, SLE disease activity index; Treg: regulatory T cells; WBCs: white blood cells.

Soluble Receptor Level of Advanced Glycation (sRAGE) Products in Serum in Patients with Systemic Lupus Erythematosus:

Introduction: Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by antibody formation against nuclear autoantigens. Many molecules play a role in etiopathogenesis. A receptor for Advanced Glycation (RAGE) is produced by many immune system cells, such as neutrophils, macrophages, and T cells, and interacts with many classes of ligands. For example, studies have shown that the interaction of the receptor with the HMG1 (High mobility group box-1) ligand induces the production of type 1 interferon (IFN), which plays a crucial role in the pathogenesis of SLE. In light of these results, the level of sRAGE, the soluble form of RAGE, may be associated with disease activity. In light of this information, we aimed to evaluate whether there is a relationship between plasma sRAGE levels and SLE. Methods: Eighteen patients diagnosed with SLE (M/F: 1/17) and twenty-one patients without any disease diagnosis (M/F: 2/19) were included as the control group. Four patients were classified as inactive SLE and fourteen as active SLE according to the SLE Disease Activity Index (SLEDAI) classification criteria. In these patients, plasma sRAGE level was measured by ELIZA method using ELIZA (enzyme-linked immunosorbent assay) kit (BioVendor Research and Diagnostic Products). The data obtained were compared between the groups. Conclusion: The mean plasma sRAGE level was lower in patients with SLE than in healthy control patients but not statistically significant (p=0.966). Our study found a positive correlation between SLEDAI and sRAGE levels in patients with SLE (r=0.628, p=0.005). Although no significant correlation was found between patients with SLE, sRAGE levels were positively correlated between fourteen patients classified as active SLE and the control group. sRAGE levels were statistically significantly higher in patients with active SLE (r=0.695, p=0.001). Discussion: In our study, we found that plasma sRAGE levels in patients with SLE were lower than in healthy controls, but plasma sRAGE levels in patients with active SLE were higher than plasma sRAGE levels in patients with inactive SLE. We hypothesized that reduced sRAGE levels in patients with SLE could be explained by the depletion of this soluble receptor. sRAGE-ligand complexes have been suggested to be eliminated from the blood via the spleen and liver. It is also possible that sRAGE levels in SLE patients are adjusted by alternative splicing and proteinases, and this possibility needs to be clarified in future investigations. Our study differed from another similar study showing that blood sRAGE levels were higher in patients with SLE than in healthy controls. Blood sRAGE levels were significantly increased during active disease compared with patients with quiescent SLE. The medication use of the patients and the small number of patients may explain this discrepancy.

Serum salusin-β levels in patients with systemic lupus erythematosus.

Endothelial dysfunction (ED) has an important role in the pathogenesis of systemic lupus erythematosus (SLE). Studies on other inflammatory diseases show that salusin-β with various mechanisms may play a role in the promotion of ED and inflammation. The aim of this study was to measure serum salusin-β levels in SLE patients and evaluate it as a potential biomarker in assessing SLE activity and predicting organ involvement. In a cross-sectional study, 60 patients diagnosed with SLE and 30 age- and sex-matched healthy controls were enrolled. Disease activity of SLE patients was assessed by the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K). Serum levels of salusin-ß were measured using a human salusin-ß enzyme-linked immunosorbent assay kit. Serum salusin-β levels in SLE and control groups were 474.2 ± 117.1pg/ml and 157.7 ± 88.7pg/ml, respectively. The difference was significant (P = 0.001). There was no significant correlation between serum salusin-β levels with age (r = - 0.06, P = 0.632) and SLEDAI (r = - 0.185, P = 0.158). In patients with nephritis and thrombosis, serum salusin-β was significantly higher. In addition, in patients with serositis, serum salusin-β was significantly lower. Multiple linear regression analysis showed that serum salusin-β levels retained a significant association with nephritis and thrombosis after model adjustment for serositis, nephritis, and thrombosis. Our findings showed that salusin-β might have a possible role in the pathogenesis of SLE. Salusin-β may be a potential biomarker for nephritis and thrombosis in SLE. Key Points • Serum salusin-β levels were significantly higher in SLE patients than the control group. • There was no significant correlation between serum salusin-β levels with age and SLEDAI. • Serum salusin-β levels retained a significant association with nephritis and thrombosis.

Effect of Systemic Lupus Erythematosus and Immunosuppressive Agents on COVID-19 Vaccination Antibody Response.

The risk of COVID-19 infection is increased in patients with systemic lupus erythematosus (SLE) versus those without SLE. Some immunosuppressive medications increase COVID-19 infection and decrease the efficacy of vaccination. Consensus documents have suggested management strategies for handling immunosuppressive medications to increase vaccine efficacy, but the benefit of such strategies has not been proven. The current study was undertaken to determine the effect of immunosuppressive drugs on vaccine response in SLE. We collected information on COVID-19 infection, vaccination history, and COVID-19 antibodies in the Hopkins Lupus Cohort. A cohort of health care workers was used for comparison. Outcome measures included SARS-CoV-2 antibody IgG levels after vaccination over time in both cohorts and effect of immunosuppressive medications on postvaccination IgG levels in SLE patients. The analysis was based on 365 observations from 334 different patients in the SLE cohort, and 2,235 observations from 1,887 different health care workers. SLE patients taking immunosuppressive medications had lower vaccine IgG levels than SLE patients who were not; but both groups had lower levels than health care workers. Holding mycophenolate for 1 week after vaccination increased postvaccine IgG levels significantly without leading to clinical flares. In multiple variable models, mycophenolate mofetil, tacrolimus, and belimumab all significantly reduced antibody response to vaccination. SLE patients, regardless of background immunosuppressive therapy, had lower vaccine IgG levels than health care workers. Mycophenolate, tacrolimus, and belimumab significantly reduced IgG response to vaccination. Holding mycophenolate for 1 week improved vaccine efficacy, providing clinical benefit on vaccine response without leading to clinical flares.

Steroid Resistance Associated with High MIF and P-gp Serum Levels in SLE Patients.

Approximately 30% of patients with systemic lupus erythematosus (SLE) present steroid resistance (SR). Macrophage migration inhibition factor (MIF) and P-glycoprotein (P-gp) could be related to SR. This work aims to evaluate the relationship between MIF and P-pg serum levels in SR in SLE. Methods: Case–control study including 188 SLE patients who were divided into two groups (90 in the steroid-resistant group and 98 in the steroid-sensitive (SS) group) and 35 healthy controls. MIF and P-gp serum levels were determined by ELISA. Multivariable logistic regression and chi-squared automatic interaction detection (CHAID) were used to explore risk factors for SR. Results: The steroid-resistant group presented higher MIF and P-gp serum levels in comparison with the SS (p < 0.001) and reference (p < 0.001) groups. MIF correlated positively with P-gp (rho = 0.41, p < 0.001). MIF (≥15.75 ng/mL) and P-gp (≥15.22 ng/mL) were a risk factor for SR (OR = 2.29, OR = 5.27). CHAID identified high P-gp as the main risk factor for SR and high MIF as the second risk factor in those patients with low P-gp. Conclusions: An association between MIF and P-gp serum levels was observed in SR. CHAID identified P-gp ≥ 15.22 ng/mL as the main risk factor for SR. More studies are needed to validate these results.

High mobility group box protein 1 (HMGB1) serum and urinary levels and gene polymorphism in Egyptian patients with systemic lupus erythematosus: A possible relation to lupus nephritis.

The aim of this study was to evaluate the effects of the high mobility group box protein 1 (HMGB1) serum and urinary levels and gene polymorphisms on systemic lupus erythematosus (SLE) development and investigate their link to lupus nephritis (LN). We enrolled 120 Egyptian SLE patients and 120 healthy controls. Thorough medical and clinical evaluation were carried out, and SLE disease activity index (SLEDAI) was assessed. Lupus patients were divided into two groups according to the presence of LN. Measurement of HMGB1 serum and urinary levels was done using ELISA and genotyping for HMGB1 (rs1045411) was performed. There were statistically significantly higher HMGB1 serum and urinary levels in SLE patients (p < 0.001). There was a marginally significant association between lupus and alleles (p = 0.059, φ = -0.086). 'C' allele was marginally significant risk allele for SLE. After classifying SLE patients based on the presence or absence of LN, there was no significant difference as regard sex (p = 0.387), age (p = 0.208) and disease duration (p = 0.094).However, there was a significant difference between the 2 groups in regard to the frequency of musculoskeletal manifestations (p = 0.035), SLEDAI score (p < 0.001), both serum (p < 0.001) and urinary HMGB1 levels (p < 0.001) in addition to the frequency of HMGB1 genotypes (p = 0.003). Lupus patients with C/T-T/T HMGB1 genotypes had 3.5-times higher odds to exhibit LN. Serum and urine HMGB1 measurements are helpful in the diagnosis of SLE and the prediction of LN. There is a link between HMGB1 gene variations and the risk of SLE, with evidence that the C/T-T/T HMGB1 genotype is linked to a significantly greater risk of LN in the Egyptian population.

The Correlation between Total Alkaline Phosphatase and Osteocalcin Levels in Systemic Lupus Erythematosus Patients

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune inflammatory disease with various complications, including osteoporosis. However, Bone Mineral Density (BMD) examination, a gold standard for diagnosing and monitoring osteoporosis, is static. Alkaline phosphatase (ALP) is a membrane-bound glycoprotein that catalysis the hydrolysis of monoester phosphate. Osteocalcin (OC) is a non-collagenic bone protein that binds calcium and phosphate, which are both dynamic bone formation activity markers. This study analyzes the correlation between total ALP and OC serum levels in SLE patients. A cross-sectional observational analytic study was conducted in the Clinical Pathology Installation of Dr. Moewardi Hospital Surakarta in June 2020. The subjects were SLE patients receiving Methylprednisolone (MEP) therapy ≥1 year. Data distribution normality test by Saphiro-Wilk, comparative analysis with unpaired T-test, degree of correlation strength between research variables by Pearson correlation test. There were 41 female subjects, and comparative analysis of total ALP and serum OC levels were not significantly different in inactive and active SLE (ALP p=0.373, serum OC p=0.700). Total ALP and serum OC was found to have a weak positive correlation in all SLE patients (r=0.337; p=0.031), a moderate positive correlation in active SLE (r=0.426; p=0.043), while in inactive SLE there was no significant correlation (r=0.247; p=0.324). There is a significant moderate positive correlation between total ALP and serum OC in SLE patients. Total ALP and serum OC examinations are necessary for osteoporosis screening in SLE patients with &gt; 1-year glucocorticoid (GC) therapy.

Assessment of Serum Neutrophil Gelatinase Associated Lipocalin (NGAL) levels in patients of Systemic Lupus Erythematosus (SLE) with and without Lupus Nephritis (LN)

Background: Lupus nephritis (LN) can occur as a complication of SLE causing further distress to patient. NGAL levels can help in foreseeing kidney injury in such afflicted. Thus, the study aimed to estimate serum NGAL levels in SLE patients with and without Lupus Nephritis. Methods: A cross sectional study was conducted at immunology Department, University of Health Sciences (UHS) Lahore. Purposive sampling technique was used to collect samples of patients diagnosed with SLE with and without Lupus Nephritis LN. Results: Study showed statistically significant results (p=0.00) with mean ±SD value of NGAL measured in patients of SLE with LN &amp; without Lupus Nephritis LN. Conclusion: The study indicated that NGAL level was observed to be significantly raised in the patients of SLE with lupus nephritis as compare to the patients of SLE without lupus nephritis. Keywords: Acute kidney injury, Anti-double stranded DNA antibody, Chronic kidney disease, Lupus nephritis

Ramipril Improves Endothelial Function and Increases the Number of Endothelial Progenitor Cells in Patients With Systemic Lupus Erythematosus.

Endothelial dysfunction and reduced number of endothelial progenitor cells (EPCs) in peripheral blood are contributing factors to cardiovascular disease in systemic lupus erythematosus (SLE) patients. Endothelial progenitor cell proliferation is regulated by vascular endothelial growth factor (VEGF). Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality in patients with coronary heart disease. This was a randomized trial including 37 female SLE patients without cardiovascular risk factors allocated into 2 groups: 19 patients received ramipril 10 mg/d for 12 weeks (IG) and 18 patients maintained without ramipril (CG). Endothelial function was assessed by brachial artery ultrasound measuring flow-mediated dilation, and EPCs were quantified by flow cytometry and cell culture, at baseline and after 12 weeks. Serum VEGF levels were measured by enzyme-linked immunosorbent assay. Statistical analysis was intention to treat. p < 0.05 was considered significant. After 12 weeks, higher flow-mediated dilation (6.17% vs. 11.14%, p < 0.001) was observed in IG, without change in CG (5.37% vs. 5.02%, p = 0.630). Higher number of EPC colony-forming units was also observed in IG (21.3 ± 10.4 vs. 31.6 ± 8.5, p < 0.001), without difference in CG ( p = 0.714). No difference was found in EPCs evaluated by flow cytometry. Vascular endothelial growth factor level increased after 12 weeks in IG ( p = 0.048), with no difference in CG ( p = 0.661). Ramipril improved endothelial function and increased the numbers of EPCs evaluated by cell culture and VEGF levels in SLE patients without cardiovascular risk factors. These data suggest that angiotensin-converting enzyme inhibitor bring an extra benefit beyond the hypotensive action and should be considered as a preferred antihypertensive drug in SLE patients.

Brief report on the relation between complement C3a and anti\xa0dsDNA antibody in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of a diverse array of autoantibodies and the dysfunctional activation of the complement system. The specific association between the complement component C3a (C3a) protein and antibodies specific for double-stranded DNA (anti-dsDNA), however, has not been studied in detail to date. This study was thus designed to more fully explore circulating C3a levels in SLE patients. In total, 13 SLE patients were enrolled in this study after having been diagnosed in accordance with the SLICC classification criteria, with 7 and 6 patients respectively exhibiting positivity for anti-dsDNA and anti-Sm autoantibodies. Serum complement component C1q (C1q) and C3a levels in samples from these patients were detected via Western blotting, while other serological, biochemical, and clinical parkers associated with disease activity were detected using standard laboratory techniques. The levels of serum C3a in anti-dsDNA+ patients were significantly elevated as compared to those in anti-Sm+ patients (P < 0.01), and a positive correlation between serum C3a levels and SLE Disease Activity Index scores was detected (P < 0.05, r = 0.6134). C3a levels are correlated with the degree of SLE disease activity and other clinically relevant readouts in SLE patients. C3a levels may also enable the differentiation between inactive and active SLE, while also offering value as an advantageous biomarker for thrombophilia monitoring in SLE patients.