Disease Activity In Systemic Lupus Erythematosus Patients Research Articles

Two-dimensional speckle-tracking echocardiography in left ventricular systolic function in patients with systemic lupus erythematosus.

To investigate whether two-dimensional speckle-tracking echocardiography (2DSTE) can be considered a criterion for early left ventricular (LV) systolic impairment in patients with systemic lupus erythematosus (SLE) and to further explore the association with each other. We included 38 patients with SLE and assessed the degree of disease activity according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) 2000 scoring criteria, together with 38 healthy controls who were matched by sex and age. Routine LV systolic function evaluation parameters were obtained by echocardiography as well as 2DSTE measurement of LV strain parameters to obtain global longitudinal strain (GLS) values, respectively. (I) On routine LV function parameters such as ejection fractions (EF) and left ventricular end-diastolic internal diameter (LVIDd), the SLE group and the control group did not reflect differences. In contrast, on the LV strain parameter obtained from 2DSTE measurements, the GLS values in all cardiac planes were lower in the SLE group than in the control group and showed statistically significant differences. (II) Correlation analysis showed that there was a correlation between SLEDAI and GLS, especially a meaningful correlation with GLS Avg and GLS A4C, with correlation coefficients of 0.35 and 0.47, respectively. The use of 2DSTE can detect early impaired LV systolic function in SLE patients, and GLS is progressively gaining attention as an indicator of subclinical myocardial injury and LV function in SLE patients. The correlation that exists between GLS and SLEDAI might contribute to a better assessment of cardiac involvement in SLE patients. Key Points • Cardiac involvement has become one of the major factors in the poor prognosis of SLE patients, which directly affects the mortality of SLE patients. Traditional echocardiography is difficult to detect early left ventricular function impairment, thus affecting clinicians' judgment and diagnosis. • 2DSTE can recognize subclinical myocardial injury in SLE patients at an early stage, and its derived strain parameters may be used as an indicator to evaluate myocardial involvement and reflect disease activity in SLE patients.

Correlation of hematological parameters, antibodies and cytokines with disease activity in systemic lupus erythematosus: a cross-sectional study

BackgroundThe aim of the study was to investigate the association of neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) with standard inflammation parameters, including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), complement component C3, anti-double-stranded deoxyribonucleic acid (anti-dsDNA), anti-nucleosome and anti-C1q antibodies, and serum and urinary monocyte-chemoattractant protein-1 (MCP-1) with disease activity in patients with systemic lupus erythematosus (SLE).ResultsThis study included 160 patients (145 female and 15 male patients), hospitalized at the Rheumatology Department. A positive correlation between NLR and ESR (p < 0.01), anti-dsDNA antibodies (p < 0.05), and PLR (p < 0.001) was obtained, with a negative correlation with C3 (p < 0.005). PLR shows a positive correlation with ESR (p < 0.001), CRP (p < 0.005), anti-dsDNA antibodies (p < 0.001), anti-nucleosome antibodies (p < 0.05), and urine MCP-1 (p < 0.05), with a negative correlation with C3 (p < 0.005). Univariate analysis showed that all the examined laboratory parameters were independent predictors of disease activity (p < 0.001), while the method of standard multiple regression analysis revealed the most significant ESR and serum MCP-1 (p < 0.05).ConclusionsNLR and PLR, as inexpensive and accessible biomarkers, can help in routine clinical practice for the estimation of disease activity in SLE patients.

Analysis of Hematological Indices in Patients of Systemic Lupus Erythematous and Its Correlation with SLEDAI-2K.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease which is characterized by chronic multisystem inflammation and end-organ damage. In recent times there has been a need for new hematological markers to assess disease activity in SLE patients specifically, which can be easily available like eosinophil, basophil, neutrophil, monocytes, and platelet to lymphocyte ratios (ELR, BLR, NLR, MLR, and PLR, respectively). Materials and methods: The present investigation determines the use of a different peripheral hematological marker to assess SLE activity in 106 patients attended for medical care at Sawai Mansingh (SMS) Medical College and attached hospital, Jaipur. SLE disease activity index 2000 (SLEDAI-2K) was used to assess the disease activity in all patients. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were assessed in each subject. The ratio of various hematological indices, like NLR, BLR, ELR, MLR, PLR, etc., analyzed and correlated with CRP, ESR, and SLEDAI-2K. Results: The present study revealed that the SLEDAI-2K score showed a significant positive correlation with ELR and MLR (p < 0.005). CRP showed a significant positive correlation with PLR (p < 0.005). ESR showed a significant positive correlation with ELR, MLR, PLR, and NLR (p < 0.005). Conclusion: The final results demonstrate that in SLE patients, the ratio of hematological indices like ELR, MLR, and PLR can be employed as disease activity markers. How to cite this article: Meena VP, Meena PD, Chejara RS, et al. Analysis of Hematological Indices in Patients of Systemic Lupus Erythematous and Its Correlation with SLEDAI-2K. J Assoc Physicians India 2023;71(11):40-42.

BAFF system expression in double negative 2, activated naïve and activated memory B cells in systemic lupus erythematosus.

B cell activating factor (BAFF) has an important role in normal B cell development. The aberrant expression of BAFF is related with the autoimmune diseases development like Systemic Lupus Erythematosus (SLE) for promoting self-reactive B cells survival. BAFF functions are exerted through its receptors BAFF-R (BR3), transmembrane activator calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA) that are reported to have differential expression on B cells in SLE. Recently, atypical B cells that express CD11c have been associated with SLE because they are prone to develop into antibody-secreting cells, however the relationship with BAFF remains unclear. This study aims to analyze the BAFF system expression on CXCR5- CD11c+ atypical B cell subsets double negative 2 (DN2), activated naïve (aNAV), switched memory (SWM) and unswitched memory (USM) B cells. Forty-five SLE patients and 15 healthy subjects (HS) were included. Flow cytometry was used to evaluate the expression of the receptors in the B cell subpopulations. Enzyme-linked immunosorbent assay (ELISA) was performed to quantify the soluble levels of BAFF (sBAFF) and IL-21. We found increased frequency of CXCR5- CD11c+ atypical B cell subpopulations DN2, aNAV, SWM and USM B cells in SLE patients compared to HS. SLE patients had increased expression of membrane BAFF (mBAFF) and BCMA receptor in classic B cell subsets (DN, NAV, SWM and USM). Also, the CXCR5+ CD11c- DN1, resting naïve (rNAV), SWM and USM B cell subsets showed higher mBAFF expression in SLE. CXCR5- CD11c+ atypical B cell subpopulations DN2, SWM and USM B cells showed strong correlations with the expression of BAFF receptors. The atypical B cells DN2 in SLE showed significant decreased expression of TACI, which correlated with higher IL-21 levels. Also, lower expression of TACI in atypical B cell DN2 was associated with high disease activity. These results suggest a participation of the BAFF system in CXCR5- CD11c+ atypical B cell subsets in SLE patients. Decreased TACI expression on atypical B cells DN2 correlated with high disease activity in SLE patients supporting the immunoregulatory role of TACI in autoimmunity.

BAFFR expression in circulating T follicular helper (CD4+CXCR5+PD-1+) and T peripheral helper (CD4+CXCR5-PD-1+) cells in systemic lupus erythematosus.

Circulating T follicular helper (cTfh) and T peripheral helper (Tph) subpopulations are shown to be higher in systemic lupus erythematosus (SLE) patients and have been involved in promoting extrafollicular B cell responses. However, a possible association with the B cell activating factor (BAFF), a cytokine mainly related to B cell responses and disease activity in SLE, has not been investigated. Therefore, this study aimed to evaluate the association of cTfh and Tph subpopulations with the BAFF system expression and clinical activity in SLE patients. This study included 43 SLE patients and 12 healthy subjects (HS). The identification of cTfh (CD4+CXCR5+PD-1+), Tph (CD4+CXCR5-PD-1+) cells, expression of membrane-bound BAFF (mBAFF), BAFFR, TACI, BCMA, and intracellular IL-21 was performed by flow cytometry. Serum levels of IL-21, CXCL13, and BAFF were analyzed using ELISA. The SLEDAI-2K score was used to evaluate disease activity in SLE patients. Compared with HS, SLE patients showed a significantly increased percentage of cTfh and Tph cells, higher in patients with clearly active disease. SLE patients had markedly higher IL-21-producing cTfh and Tph cells than HS. Both subpopulations were positively correlated with the disease activity in SLE patients. Tph cells were negatively correlated with CD19+CXCR5+ B cells and positively correlated with CD19+CXCR5- B cells. A low expression of mBAFF and their receptors TACI and BCMA was found on cTfh and Tph cells in SLE patients and HS. However, SLE patients with clearly active disease showed decreased expression of BAFFR on cTfh and Tph subpopulations than patients with mildly active/nonactive disease. Serum IL-21, CXCL13, and BAFF levels were higher in SLE patients than in HS. Levels of CXCL13 were correlated with disease activity. Non-significant correlations were observed among T cell subpopulations and IL-21, CXCL13, and BAFF levels. This study emphasizes the importance of cTfh and Tph cells in SLE pathogenesis. Besides the importance of IL-21, our results suggest that BAFFR could play a role in cTfh and Tph subpopulations in the autoimmunity context.

Allogenic Umbilical Cord-Derived Mesenchymal Stromal Cells Sustain Long-Term Therapeutic Efficacy Compared With Low-Dose Interleukin-2 in Systemic Lupus Erythematosu.

Mesenchymal stromal cells (MSCs) and low-dose interleukin-2 (IL-2) both have demonstrated efficacy in treating systemic lupus erythematosus (SLE). The aim of this study is to conduct a head-to-head comparison between the 2 treatments and provide insights for clinical applications. Lupus-prone mice were treated with umbilical cord-derived MSCs (UC-MSCs), IL-2, or a combination of UC-MSCs and IL-2, respectively. The lupus-like symptoms, renal pathology, and T-cell response were assessed 1 or 4 weeks later. Modulation of IL-2 production by MSCs on immune cells was investigated by the coculture assay. Disease activity and serum IL-2 of SLE patients were determined before and after receiving UC-MSCs. Both UC-MSCs and IL-2 improved lupus symptoms in lupus-prone mice 1 week after treatment, while the effects of UC-MSCs lasted up to 4 weeks. Moreover, the UC-MSC-treated group showed better renal pathology improvement. Importantly, UC-MSCs combined with IL-2 did not provide better efficacy than UC-MSCs alone. Consistent with this, UC-MSCs alone and UC-MSCs + IL-2 resulted in similar levels of serum IL-2 and frequencies of Tregs. Neutralization of IL-2 partly reduced the promotion of Tregs by UC-MSCs, suggesting that IL-2 was involved in the upregulation of Tregs by UC-MSCs. Lastly, an increase in serum IL-2 positively correlated with the reduction of disease activity of SLE patients by UC-MSCs. Both the single injection of UC-MSCs and repeated IL-2 administration exerted comparable efficacy in alleviating SLE manifestations, but UC-MSCs provided sustained alleviation and showed better improvement in renal pathology.

Fecal microbiota transplantation attenuates hypertension in a female mouse model of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a prototypic multisystem autoimmune disorder that disproportionately affects women. SLE is characterized by a breach of immunological self-tolerance and the expansion of autoreactive T and B lymphocytes, leading to the production of autoantibodies. Autoantibody production leads to downstream chronic inflammation resulting in high rates of hypertension, renal injury, and cardiovascular disease. Alterations in the gut microbiota, or gut dysbiosis, is associated with many autoimmune diseases, including SLE. In the present study, we hypothesized that gut dysbiosis in SLE may play a role in the development of immune system dysfunction and hypertension in an experimental model of SLE, and that fecal microbiota transplantation (FMT) with microbes from control mice may improve these parameters. To test this hypothesis, we treated 26-week-old female control (NZW, n=19) and SLE (NZBWF1, n=19) mice with broad spectrum antibiotics (0.4 g/L ampicillin, 0.4 g/L neomycin sulfate, 0.4 g/L metronidazole, and 0.2 g/L vancomycin) in drinking water for one week to deplete the existing microbiota. Subsequently, mice were given 0.1 mL of fecal microbes via oral gavage two times per week for four weeks in the following groups (n=9-10 mice/group): Control-vehicle, Control-SLE microbes, SLE-vehicle, SLE-Control microbes. Changes in the gut microbiome before and after FMT were assessed by 16S rRNA analysis of the microbiome. Mean arterial pressure (MAP, mmHg), measured in conscious mice by carotid artery catheter was higher in SLE mice that received SLE microbes (Control: 112±3 vs. SLE: 140 ±2 mmHg, p&lt;0.0001). SLE mice that received FMT with control microbes had lower blood pressure (SLE-Control microbes: 126±4 mmHg, p=0.03). Renal injury, as assessed by urinary albumin excretion at the conclusion of the study, was not significantly different among the groups (p=0.3523). Circulating autoantibodies and immunoglobulins were also measured at the conclusion of the study. Anti-dsDNA IgG was elevated in SLE mice compared to control (Control: 149±38 vs. SLE: 527±114 kU/mL, p=0.02), and were significantly lower in SLE mice treated with control microbes (SLE-Control microbes: 126±4 mmHg, p=0.03). Circulating IgM was also elevated in SLE mice (Control: 0.053±0.008 vs. SLE: 0.32±0.04 mg/mL, p&lt;0.0001), and FMT lowered IgM in SLE mice that received FMT (0.19±0.03 mg/mL, p=0.0069). These data suggest that gut microbiota present in NZBWF1 mice contribute to both autoantibody production and the development of hypertension, and that interventions to alter the microbiora could have a beneficial impact on disease activity in SLE patients. NIH NIGMS P20GM104357 to UMMC Department of Physiology and Biophysics, NIH NHLBI R00HL146888 to Erin Taylor This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

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.

Correlation Between Gene Expression of Interferon Regulatory Factor-5 and Disease Activity Index in Systemic Lupus Erythematosus Iraqi Patients

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by elevated levels of circulating anti-nuclear autoantibodies and interferon-alpha (INFs-α). Interferon regulatory factor-5 (IRF5) plays an important role in the induction of type I interferon and pro-inflammatory cytokines, and participates in the SLE pathogenesis. This study aimed to investigate the role of IRF5 gene expression levels in a sample of SLE Iraqi patients and its correlation with disease activity, and to identify its diagnostic ability as a biomarker reflecting disease activity. Blood samples were taken from 45 participants diagnosed with SLE cases classified according to the American College of Rheumatology (ACR) criteria. They were scored via the SLE disease activity index 2000 (SLEDAI-2K) to assess the disease activity and according to it, they were subdivided into “SLE (I) group” (SLEDAI-2k ≤5), and “SLE (II) group” (SLEDAI-2k &gt;5), as well as age and gender matched healthy control group. RNA was isolated from whole blood samples and gene expression levels of IRF5 were determined using real-time polymerase chain reaction (PCR). Our results revealed that the expression levels of the IRF5 gene were significantly increased in SLE (I) and SLE (II) patient groups compared with the control group (p&lt;0.05, and p&lt;0.01) respectively, as well as higher in SLE (II) group than the SLE (I) group (p&lt;0.01). Moreover, the expression levels of IRF5 were found to be related positively and significantly to the disease activity index in both SLE patient groups. The analysis of receiver operator curves (ROC) for gene expression levels of IRF5 in SLE (II) group showed a perfect accuracy to distinguish between SLE patients and healthy individuals (AUC=0.989, sensitivity= 95.5%, and specificity= 88.0%). However, in SLE (I) group showed a good accuracy to discriminate between SLE patients and healthy individuals. (AUC=0.769, sensitivity= 69.6%, and specificity= 80.0%). The correlation between gene expression levels of IRF5 with other parameters revealed that a significant positive correlation was found with uric acid and ALP in SLE (I) group, while in SLE (II) group with urea, creatinine, and uric acid. Our conclusion suggests that the up-regulation of IRF5 gene expression levels correlates positively with disease activity in SLE patients reflecting the possibility of using it as an immunological biomarker for diagnosis, and monitoring the disease flare.

Circulating levels of Interferon regulatory Factor-5 correlates with disease activity in Systemic Lupus Erythematosus Iraqi patients

Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by a diversity of the phenotypes among the patients. SLE is still one of the great challenges due to the lacking of specific biomarkers for diagnosis, assessing disease activity, and prediction of response to therapy. This study aimed to investigate the role of circulating levels of IRF5 protein in sample of SLE Iraqi patients and its correlation with disease activity, to identify a potential immunological biomarker to mirror disease activity.&#x0D; Methods: Blood samples were taken from 59 participants diagnosed with SLE cases classified according to the American College of Rheumatology (ACR) criteria. They were scored through the SLE disease activity index 2000 (SLEDAI-2K) to estimate the disease activity, and according to it they were subdivided into “SLE-1 group” (SLEDAI-2k ≤5), and “SLE-2 group” (SLEDAI-2k &gt;5), as well as age and gender matched healthy control group. Circulating levels of IRF5 protein were measured in sera samples by ELISA method.&#x0D; Results: Our result revealed that the circulating levels of IRF5 protein were significantly higher in the SLE-2 group rather than control group (p&lt;0.01), while there was a non-significant difference between SLE-1 group and control group (p&gt;0.05), as well as between both SLE patient groups. Moreover, the circulating IRF5 protein levels were found to be correlated positively and significantly with disease activity index in both SLE patient groups. The correlation between the circulating levels of IRF5 protein with other parameters revealed that a significant positive correlation was found in SLE-1 group with ESR and globulins, and negative correlation with Hb and (albumin/ globulin) ratio, while in SLE-2 group were positively correlated with urea, creatinine, and uric acid. The analysis of receiver operator curves (ROC) for circulating levels of IRF5 protein in SLE-1 and SLE-2 groups showed a good accuracy to distinguish SLE patients from healthy individuals (AUC=0.758, sensitivity=65.5%, and specificity=69%,), and (AUC=0.788, sensitivity=77.3%, and specificity=72.0%,), respectively.&#x0D; Conclusions: The circulating levels of IRF5 protein correlate with disease activity in SLE patients reflects the possibility of using it as a potential immunological biomarker for diagnosis, and monitoring the disease activity.

Potential biomarkers for active renal involvement in systemic lupus erythematosus patients.

This study aimed to identify the key genes related to active renal involvement in patients with systemic lupus erythematosus (SLE). Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between SLE patients with active renal involvement and those who did not have active renal involvement were identified by R software. Hub genes were identified using protein-protein interaction networks. The relationships between the expression levels of identified hub genes and SLEDAI were subjected to linear correlation analysis. The diagnostic accuracy of the hub genes was evaluated with the area under the curve of the receiver operating characteristic curve (ROC-AUC). Transcription factors (TFs) were predicted. The expression levels of different hub genes and histopathological patterns were also examined. A total of 182 DEGs were identified. Enrichment analysis indicated that DEGs were primarily enriched in neutrophil degranulation, neutrophil activation involved in immune response and neutrophil activation. The expression levels of 12 identified hub genes were verified. Ten of the 12 hub genes were positively associated with SLEDAI. The combination model of DEFA4, CTSG, RETN, CEACAM8, TOP2A, LTF, MPO, ELANE, BIRC5, and LCN2 had a certain diagnostic accuracy in detecting renal involvement with high disease activity in SLE patients. The expressions of five predicted TFs were validated by GSE65391 dataset. This work explored the pathogenesis of renal involvement in SLE. These results may guide future experimental research and clinical transformation.

Altered PTPN22 and IL10 mRNA Expression Is Associated with Disease Activity and Renal Involvement in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with very heterogeneous clinical behavior between affected individuals. Therefore, the search for biomarkers clinically useful for the diagnosis, prognosis, and monitoring of the disease is necessary. Here, we determined the association between PTPN22, IL10, OAS2, and CD70 mRNA expression with the clinical characteristics and with the serum levels of IL-10, IFN-γ, and IL-17 in SLE patients. Forty patients with SLE and 34 control subjects (CS) were included, mRNA expression was determined by real-time qPCR and cytokine levels were quantified by a multiplex bead-based immunoassay. Compared to CS, SLE patients showed increased IL10 mRNA and high IL-10 and IL-17 serum levels; in contrast, PTPN22 mRNA and IFN-γ were decreased. PTPN22 and IL10 gene expression was negatively correlated with Mex-SLEDAI score and were notably downregulated in SLE patients with lupus nephritis. Interestingly, SLE patients with renal damage were the ones with the lowest levels of PTPN22 and IL10 mRNA and the highest SLEDAI scores. No associations were observed for OAS2 and CD70 mRNA and IL-10, IL-17, and IFN-γ. In conclusion, we suggest that the assessment of IL10 and PTPN22 mRNA could be useful for monitoring disease activity in SLE patients showing renal involvement.

Association of - 717 A > G (rs2794521) CRP polymorphism with high cardiovascular risk by C-reactive protein in systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is an autoimmune disease where genetic factors have been related to SLE susceptibility and disease severity. CRP polymorphisms have been associated with high C-reactive protein (CRP) serum levels, cardiovascular disease (CVD), and high clinical disease activity in SLE patients; however, the evidence is still inconclusive. This study was aimed to assess the association of the - 717 A > G, - 409 G > A, + 1444 C > T, and + 1846 C > T CRP polymorphisms with genetic susceptibility, clinical disease activity, and CVD risk in Mexican-mestizo SLE patients. A comparative cross-sectional study was conducted on 369 unrelated women: 183 with SLE according to the 1997 SLE-ACR criteria and 186 healthy subjects (HS). The clinical disease activity was assessed by the Mex-SLEDAI score; CRP and lipid profile were quantified by turbidimetry and colorimetric-enzymatic assays, respectively. The CRP polymorphisms genotyping was carried out by allelic discrimination. SLE patients with - 717 AA genotype had higher CRP serum levels than SLE carriers of AG and GG genotypes (AA = 5mg/L vs. AG = 3.2mg/L vs. GG = 2.4mg/L; p = 0.01), and the AA genotype was associated with high CVD risk by CRP in SLE patients (OR = 3; CI: 1.2-7.6; p < 0.01). The - 717 A > G CRP polymorphism is a risk factor for high CRP levels and high CVD risk in Mexican-mestizo SLE patients. Key Points • Cardiovascular disease is one of the major causes of death in SLE patients due to the higher prevalence of traditional and non-traditional cardiovascular risk factors. • C-reactive protein is a liver-derived acute-phase protein suggested as one powerful independent risk predictor factor for cardiovascular disease. • Single nucleotide polymorphisms in CRP have been suggested as genetic susceptibility factors that could modify the SLE pathophysiology outcomes. • Mexican-mestizo SLE patients carrying the -717 A>G CRP AA genotype had 3-fold high cardiovascular disease risk than SLE patients with AG or GG genotypes.

Vitamin D Receptor (VDR) Genetic Variants: Relationship of FokI Genotypes with VDR Expression and Clinical Disease Activity in Systemic Lupus Erythematosus Patients.

Vitamin D (VD) deficiency is more frequent in systemic lupus erythematosus (SLE) patients than in control subjects (CS); genetic variants in the VD receptor (VDR) could contribute to the clinical disease activity. This study was aimed to determine the association of the VDR variants FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) with susceptibility to the disease, VD status, VDR mRNA expression, and clinical disease activity in SLE patients. A cross-sectional study was conducted in 194 SLE and 196 CS Mexican women. Immunoassays quantified serum calcidiol and calcitriol. Genotyping was performed by allelic discrimination assays and mRNA VDR expression by qPCR. The FokI variant was not in linkage disequilibrium with BsmI, ApaI, and TaqI&nbsp;VDR variants. SLE patient carriers of the TT FokI genotype showed higher clinical disease activity scores. Notably, the mRNA VDR expression was higher in SLE patients vs. CS, in active vs. inactive SLE patients, and in participants of both study groups with vitamin D deficiency, higher calcitriol levels, and TT FokI genotype carriers. In conclusion, the TT FokI VDR genotype was related to high VDR expression and clinical disease activity in systemic lupus erythematosus patients.

Notch1 signalling controls the differentiation and function of myeloid-derived suppressor cells in systemic lupus erythematosus.

Emerging studies have reported the expansion of myeloid-derived suppressor cells (MDSCs) in some autoimmune disorders, such as systemic lupus erythematosus (SLE), but the detailed molecular mechanisms of the aberrant expansion in SLE are still unclear. In the present study, we confirmed that the increased MDSCs positively correlated with disease activity in SLE patients. The suppressive capacity of MDSCs from patients with high activity was lower than that of MDSCs from patients with low activity. Moreover, the potential precursors for MDSCs, common myeloid progenitors (CMPs) and granulocyte-monocyte progenitors (GMPs), were markedly increased in the bone marrow (BM) aspirates of SLE patients. As an important regulator of cell fate decisions, aberrant activation of Notch signalling was reported to participate in the pathogenesis of SLE. We found that the expression of Notch1 and its downstream target gene hairy and enhancer of split 1 (Hes-1) increased markedly in GMPs from SLE patients. Moreover, the Notch1 signalling inhibitor DAPT profoundly relieved disease progression and decreased the proportion of MDSCs in pristane-induced lupus mice. The frequency of GMPs was also decreased significantly in lupus mice after DAPT treatment. Furthermore, the inhibition of Notch1 signalling could limit the differentiation of MDSCs in vitro. The therapeutic effect of DAPT was also verified in Toll-like receptor 7 (TLR7) agonist-induced lupus mice. Taken together, our results demonstrated that Notch1 signalling played a crucial role in MDSC differentiation in SLE. These findings will provide a promising therapy for the treatment of SLE.

An evaluation of anifrolumab for use in adults with systemic lupus erythematosus

ABSTRACT Introduction Type 1 interferons play a key role in the pathogenesis of systemic lupus erythematosus (SLE). An important clinical question is whether inhibiting the type 1 interferon pathway reduce the disease activity in SLE patients. This review evaluates the safety and efficacy of the monoclonal antibody against the type 1 interferon alpha receptor, anifrolumab, in patients with SLE. Areas covered Key terms (SLE, type 1 interferon, anifrolumab) were used to query the PubMed database for phase 1, 2 and 3 clinical trials of anifrolumab for SLE patients. Phase 1 studies showed anifrolumab has non-linear pharmacokinetics and the optimal safe dose is 300 mg given intravenously every four weeks. The MUSE (phase 2) and the TULIP-2 (phase 3) trials showed that anifrolumab when added to standard therapy significantly reduced disease activity in SLE patients. Common adverse events associated with anifrolumab were upper respiratory and urinary infections as well as shingles. Expert opinion Anifrolumab is an exciting new therapeutic for SLE patients. Additional analyses of the combined TULIP-1 and TULIP-2 datasets as well as future studies with anifrolumab will generate yet more data in SLE. No doubt anifrolumab will be studied in other diseases where type I interferons play an important role.

A cluster of type II interferon-regulated genes associates with disease activity in patients with systemic lupus erythematosus

Upregulation of interferon-regulated genes (IRGs), denoted IFN signature, in peripheral blood has been used as an indirect measure of IFN pathway activation in patients with systemic lupus erythematosus (SLE). However, it has not been determined, which IFN signatures that optimally reflect clinical disease activity.In this study, we determined an IFN signature based on the expression of 128 IRGs in whole blood from 34 SLE patients in a cross-sectional (CS) study, 11 with active lupus nephritis followed longitudinally (LS) and 15 healthy controls. Blood samples were collected in PAXgene tubes and RNA was extracted and purified using a PAXgene blood RNA kit (Qiagen). Gene expression was measured using the NanoString nCounter Gene Expression platform.The CS SLE patients with higher disease activity displayed thrice as many upregulated IRGs (n = 46) as the rest. These IRGs clustered in three groups, consisting of IRGs known to be predominantly stimulated by type I (gene cluster K1) and type II (gene clusters K2 and 3) IFNs. SLEDAI-2K scores associated with the K2 and K3 gene scores (β = 0.372 and β = 0.419, both p < 0.015) but not with K1. In the longitudinal study, the mean SLEDAI-2K score decreased after an average follow-up of 360 days (β = −2.08, P = 5.09 × 10−12). The mean K1, K2 and K3 gene scores did not change over time, however longitudinal changes in SLEDAI-2K and K3 scores were associated (β = 0.814, p = 0.007).This study validates the presence of type I IRG subsets that do not associate with disease activity in SLE patients. The novel finding in this study is the association between a type II IRG subset and disease activity. Both findings may have significant implications for choosing IRGs defining clinically relevant IFN signatures.

Evolving phenotype of systemic lupus erythematosus patients and it's correlation with antibody against c1q

Backgrounds: Autoantibodies against C1q are strongly linked to immune-complex disorders like systemic lupus erythematosus (SLE). Although anti-C1q antibodies have received much interest in the recent years, their biological functions remain unclear. Aim and objectives: The main aim of this study was to analyze the phenotype of systemic lupus erythematosus at first presentation and during follow-up at Qena university hospital. Subjects and methods: This cross-sectional study was conducted at Qena university hospital. The study was conducted on 100 systemic lupus erythematosus patients. Results: Regarding the relation between lupus activity and anti-C1q antibody we found that there were highly statistically significant differences between lupus activity groups according to anti-C1q antibody. We also found that there were highly statistically significant differences between lupus activity groups according to anti-C1q with highly increasing in anti-C1q in patients with lupus activity when comparing with patients without lupus activity. Conclusion: Anti-C1q antibodies were strongly associated with lupus disease activity in SLE patients, suggesting that it may be a reliable, sensitive and non-invasive serological marker for identification of SLE patients with active SLE disease.

Evaluation of thiol/disulfide hemostasis and serum Ischemia modified albumin as oxidative stress biomarkers in systemic lupus erythematosus patients: Relationship with major organ involvement and disease activity.

We aimed to compare thiol/disulfide hemostasis and serum ischemia-modified albumin (IMA) levels, which are indicators of oxidative stress (OS), in patients with systemic lupus erythematosus (SLE), with the healthy control (HC) group and to evaluate the relationship of these parameters with disease activity and major organ involvement. Eighty-four SLE patients and 96 HCs were included in this study. The disease activity of SLE patients was calculated using The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Patients with SLEDAI-2K ≤ 5 were classified as low disease activity (LDA) and those with SLEDAI-2K > 6 as high disease activity (HDA). Thiol/disulfide hemostasis was evaluated using a new automated method and natural thiol (NT), total thiol (TT), disulfide (SS) levels, SS/NT, SS/TT, NT/TT ratios, and serum IMA levels were recorded. NT and TT levels were significantly lower (490.11 ± 123.61 vs 536.96 ± 86.05, p = 0.003) (532.56 ± 125.80 vs 565.72 ± 89.82, p = 0.046), SS level (21.22 ± 11.75 vs 13.37 ± 9.31, p < 0.001) was higher, and SS/TT (4.64 ± 2.93 vs 2.52 ± 1.82, p < 0.001) and SS/NT (4.12 ± 2.33 vs 2.35 ± 1.59, p < 0.001) ratios were significantly higher in SLE patients compared to HCs. IMA values were not different between the two groups (p = 0.920). NT (449.84 ± 136.98 vs 520.32 ± 104.11, p = 0.012) and TT levels (492.01 ± 138.45±562.97 ± 107.09, p = 0.013) were significantly lower and serum IMA levels (0.802 ± 0.089 vs 0.764 ± 0.040, p = 0.023) were significantly higher in SLE patients with HDA than in LDA patients. There was a weak negative correlation between NT (r = -0.284, p=0.009) (r = -0.291, p = 0.007) and TT levels (r = -0.281, p = 0.010) (r = -0.289, p = 0.008) and a weak positive correlation between IMA levels (r = 0.279, p = 0.011) (r = 0.263, p = 0.016) and SLEDAI-2K, and major organ involvement. It is thought that thiol/disulfide hemostasis and IMA levels may be used as ideal biomarkers of OS in SLE patients and may reflect the disease activity and major organ involvement.

Mean platelet volume to lymphocyte ratio and platelet distribution width to lymphocyte ratio in Iraqi patients diagnosed with systemic lupus erythematosus.

IntroductionThe mean platelet volume to lymphocyte ratio (MPVLR) and platelet distribution width to lymphocyte ratio (PDWLR) have the potential to serve as markers of inflammation which may indicate disease activity. The mean platelet volume to lymphocyte ratio and PDWLR were assessed in patients with systemic lupus erythematosus (SLE) in this study.Material and methodsSixty-two patients with systemic lupus erythematosus and 79 controls who were age and gender matched were included. Their sociodemographic information, as well as disease activity scores based on the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), disease duration, current medications, lymphocytes, platelets, platelet distribution width (PDW), and mean platelet volume (MPV), anti-nuclear antibody (ANA), anti-double stranded deoxyribonucleic acid (anti-dsDNA), and complement components (C3, C4) were recorded. The correlations of MPVLR and PDWLR with disease activity and some laboratory parameters were analyzed.ResultsLupus patients had significantly higher median (interquartile range) values for MPVLR and PDWLR than controls (5.69 [1.16–23.67] vs. 4.40 [2.78–11.93], p = 0.009) and 10.51 (2.87–79.37) vs. 5.21 (2.88–14.66), p < 0.001] respectively. According to the ROC curve, > 7.53 was the best PDWLR cut-off value for predicting SLE with a sensitivity of 71%, a specificity of 87% and an accuracy of 82.6%, whereas the optimum MPVLR cut-off value was > 6.46 with a sensitivity of 45.2%, a specificity of 88.9% and an accuracy of 76.8%. In addition, MPVLR had a significant positive correlation with SLEDAI (r = 0.34, p = 0.008). However, there was no significant correlation between PDWLR and SLEDAI (r = 0.23, p = 0.067). Furthermore, PDWLR had a significant positive correlation with PDW (r = 0.482, p < 0.001), while MPVLR had a significant negative correlation with C3 level (r = –0.260, p = 0.042). Both PDWLR and MPVLR were positively correlated with nephritis (r = 0.388, p = 0.002; r = 0.246, p = 0.038, respectively).ConclusionsThe platelet distribution width to lymphocyte ratio can be considered as an assisting biomarker in the diagnosis of SLE with the other clinical and serological parameters. The mean platelet volume to lymphocyte ratio may be used in the evaluation of disease activity in SLE patients.