Systemic Lupus Erythematosus Subjects Research Articles

Clinical Characteristics of Patients with Primary and Secondary Fibromyalgia in Bulgaria

Fibromyalgia (FM) is characterized by a chronic widespread pain, general fatigue, anxiety, depression, sleep disturbances and functional disorders. FM affects both women and men in 9:1 to 20:1 ratio. The purpose of this clinical study is to analyze clinical manifestations in patients with primary and secondary fibromyalgia. Eighty-three patients with primary FM, 39 patients with FM and osteoarthritis (OA), 23 patients with FM and systemic lupus erythematosus (SLE), 27 patients with SLE, and 36 healthy subjects were included. The present study compared chronic pain, fatigue, depression and anxiety in patients with primary FM, patients with SLE, FM + OA, FM + SLE and healthy subjects. Based on the 2016 criteria for number of chronic widespread pain areas, there is a statistically significant difference of the control group compared to the patients with primary FM (p = 0.001), FM + OA (p = 0.001), FM + SLE (p = 0.001), SLE (p = 0.001). Based on the MFIS fatigue scale, the chronic fatigue is a statistically significant difference of the control group, as compared to patients with primary FM (p = 0.004), FM + OA (p = 0.02), FM + SLE (p = 0.001). Based on the HADS clinical parameter, anxiety and depression are a statistically significant difference of the control group, as compared to patients with primary FM (p = 0.01), FM + OA (p = 0.01), FM + SLE (p = 0.01), and no difference in patients with SLE (p = 0.77). The comparison between the patient groups is important to evaluate the disease activity and the treatment to be recommended.

Identification of immune subsets with distinct lectin binding signatures using multi-parameter flow cytometry: correlations with disease activity in systemic lupus erythematosus.

Cell surface glycosylation can influence protein-protein interactions with particular relevance to changes in core fucosylation and terminal sialylation. Glycans are ligands for immune regulatory lectin families like galectins (Gals) or sialic acid immunoglobulin-like lectins (Siglecs). This study delves into the glycan alterations within immune subsets of systemic lupus erythematosus (SLE). Evaluation of binding affinities of Galectin-1, Galectin-3, Siglec-1, Aleuria aurantia lectin (AAL, recognizing core fucosylation), and Sambucus nigra agglutinin (SNA, specific for α-2,6-sialylation) was conducted on various immune subsets in peripheral blood mononuclear cells (PBMCs) from control and SLE subjects. Lectin binding was measured by multi-parameter flow cytometry in 18 manually gated subsets of T-cells, NK-cells, NKT-cells, B-cells, and monocytes in unstimulated resting state and also after 3-day activation. Stimulated pre-gated populations were subsequently clustered by FlowSOM algorithm based on lectin binding and activation markers, CD25 or HLA-DR. Elevated AAL, SNA and CD25+/CD25- SNA binding ratio in certain stimulated SLE T-cell subsets correlated with SLE Disease Activity Index 2000 (SLEDAI-2K) scores. The significantly increased frequencies of activated AALlow Siglec-1low NK metaclusters in SLE also correlated with SLEDAI-2K indices. In SLE, activated double negative NKTs displayed significantly lower core fucosylation and CD25+/CD25- Siglec-1 binding ratio, negatively correlating with disease activity. The significantly enhanced AAL binding in resting SLE plasmablasts positively correlated with SLEDAI-2K scores. Alterations in the glycosylation of immune cells in SLE correlate with disease severity, which might represent potential implications in the pathogenesis of SLE.

Endothelin-1 Correlates with Blood Pressure and Pulse Pressure in Females with Lupus Associated Hypertension

Systemic Lupus Erythematosus (SLE) is a common autoimmune disease that is classified by IgG complex deposition in end organs including the kidney, heart, and vasculature. SLE disproportionally affects women to men (9:1 ratio), with a high prevalence in African American women. Importantly, patients with an SLE diagnosis have common cardiovascular complications including hypertension. Importantly, numerous studies have reported that plasma and urinary endothelin-1 (ET-1) levels are elevated in patients with SLE or hypertension. However, few studies have investigated the role of the synergistic effects of SLE and hypertension on ET-1. Therefore, we hypothesized that women with SLE and hypertension would have elevated plasma ET-1 levels compared to SLE or hypertension alone. To investigate this, we recruited non-SLE non-HTN controls (n=8), non-SLE HTN (n=7), SLE non-HTN (n=5), and SLE-HTN (n=6) female human subjects and analyzed clinical and demographic characteristics, plasma ET-1, c-reactive protein (CRP), soluble vascular adhesion molecule-1 (sVCAM-1), and anti-Smith autoantibodies. We found that plasma ET-1 levels are significantly higher in African American compared to European American patients independent of SLE or blood pressure status (p=0.0182). When plasma ET-1 levels were correlated with age and body mass index (BMI), ET-1 had a positive association with age (r=0.4861;p=0.0118), but no correlation with BMI (r=0.2137;p=0.2945). When subjects we characterized by SLE diagnosis, we found that female subjects with SLE had elevated plasma ET-1 levels compared to non-SLE controls (p=0.0141). Next, we stratified subjects by blood pressure status and found that only SLE-HTN subjects had significantly elevated plasma ET-1 levels compared to non-SLE non-HTN controls (p=0.0005), and a trend for elevated ET-1 levels over SLE non-HTN (p=0.0799). Lastly, we correlated plasma ET-1 levels to offce systolic blood pressure, diastolic blood pressure and calculated pulse pressure. We found that plasma ET-1 positively associated with systolic blood pressure (r=0.5621;p=0.0035) and pulse pressure (r=0.5810;p=0.0023) but not diastolic blood pressure (r=0.3177;p=0.1217). These data demonstrate that plasma ET-1 levels associate with SLE diagnosis and blood pressure status in our cohort of female SLE human subjects. Further investigation of ET signaling should be done in SLE and SLE-HTN human subjects. Veterans Affairs Biomedical Laboratory Research & Development Career Development Award (CDA-2) 1IK2BX005605-01 to J.P.V.B, Medical University of South Carolina College of Medicine Program Project Grant to J.C.O and J.P.V.B., and Medical University of South Carolina Core Centers for Clinical Research Project Award P30AR072582 to M.A.C and J.P.V.B. This is the full abstract presented at the American Physiology Summit 2024 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.

Evaluation of Serum Amyloid A and some Biochemical markers in Iraqi patients with systemic lupus erythematosus

An autoimmune condition called systemic lupus erythematosus (SLE) is caused by long-term inflammation. Amyloid A (AA) amyloidosis results in nephropathy and other internal symptoms, including death. The current study set out to look at the relationship between serum amyloid A (SAA) levels in circulation and SLE patients. Methods: Sixty SLE patients and 30 healthy with age range (19-55) yearswere involved in this study. A SLE patient wasidentified in the teaching hospital in Baghdad. In this study, laboratory indicators such as blood lipid, kidney function, test results, and total cholesterol (TC), triglyceride (TG), SAA, and ALB were assessed using an automated biochemical analyzer. Results: Patients with active SLE had serum amyloid A (SAA) values 5.83 mg/L [IQR: 2.08–10.87], 4.92 mg/L [IQR: 1.57–11.43], and 1.33 mg/L [IQR: 0.13–3.12], respectively, substantially upper than personswith inactive SLE or healthy control subjects (P < 0.001). ESR values in healthy control subjects, patients with inactive SLE, and patients with active SLE. In conclusion, the current study's findings offered more proof of SAA's potential involvement in SLE and suggested that it might be valuable biomarkers that could reveal more details about the disease's activity.

The Association of Allergy and Systemic Lupus Erythematosus as a Single Disease and an Overlapping Syndrome compared to Control Group

Allergic diseases and systemic lupus erythematosus (SLE) sometimes are being connected since both of these diseases are affected by gene-environment processes. SLE can appear coexisting with other autoimmune diseases as an overlapping syndrome. This research was done to investigate the relation of allergic diseases and SLE as a single SLE or overlapping syndrome compared to control. We collected datas from 39 SLE only, 22 overlapping syndrome SLE, and 39 non SLE subjects who had filled an online Score for Allergic Rhinitis (SFAR) questionnaire. There are significant outcomes of the existance of allergic disease (p=.007), atopic dermatitis (p=.000) and total number of allergies (p=.016) in SLE patients. There is a correlation of the appearance of allergy in SLE as a single or coexisting with other autoimmune disease compared to control group. Atopic dermatitis and the more number of allergic diseases that the one have, play role in appearing SLE.
 Bangladesh Journal of Medical Science Vol. 23 No. 02 April’24 Page : 551-554

The Association of Allergy and Systemic Lupus Erythematosus as a Single Disease and an Overlapping Syndrome compared to Control Group

Background:Allergic diseases and systemic lupus erythematosus (SLE) sometimes are being connected since both of these diseases are affected by gene-environment processes. SLE can appear coexisting with other autoimmune diseases as an overlapping syndrome.
 Objectives: This research was done to investigate the relation of allergic diseases and SLE as a single SLE or overlapping syndrome compared to control.
 Method: We collected data from 39 SLE only, 22 overlapping syndrome SLE, and 39 non SLE subjects who had filled an online Score for Allergic Rhinitis (SFAR) questionnaire.
 Results: There are significant outcomes of the existence of allergic disease (p=.007), atopic dermatitis (p=.000) and total number of allergies (p=.016) in SLE patients. There is a correlation of the appearance of allergy in SLE as a single or coexisting with other autoimmune disease compared to control group.
 Conclusion: Atopic dermatitis and the more number of allergic diseases that the one have, play role in appearing SLE.
 Bangladesh Journal of Medical Science Vol. 22 No. 04 October’23 Page : 916-919

The Inflammatory Profile Orchestrated by Inducible Nitric Oxide Synthase in Systemic Lupus Erythematosus.

(1) Background: The pathogenesis of systemic lupus erythematosus (SLE) involves complicated and multifactorial interactions. Inducible nitric oxide synthase overactivation (iNOS or NOS2) could be involved in SLE pathogenesis and progression. This study explored the relationship between NOS2-associated inflammation profiles and SLE phenotypes. (2) Methods: We developed a prospective, case control study that included a group of 86 SLE subjects, a group of 73 subjects with lupus nephritis, and a control group of 60 people. Laboratory determinations included serum C reactive protein (CRP-mg/L), enzymatic activity of NOS2 (U/L), serum levels of inducible factors of hypoxia 1 and 2 (HIF1a-ng/mL, HIF2a-ng/mL), vascular endothelial growth factor VEGF (pg/mL), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9-ng/mL), thrombospondin 1 (TSP-1-ng/mL), and soluble receptor of VEGF (sVEGFR-ng/mL). (3) Results: CRP, NOS2, HIF-1a, HIF-2a, VEGF, MMP-2, and MMP-9 were significantly increased, while TSP-1 and sVEGFR were decreased in the SLE and lupus nephritis groups compared with the control group. The variations in these biomarkers were strongly associated with the decrease in eGFR and increase in albuminuria. (4) Conclusions: The inflammatory phenotype of SLE patients, with or without LN, is defined by NOS2 and hypoxia over-expression, angiogenesis stimulation, and inactivation of factors that induce resolution of inflammation in relation with eGFR decline.

TLR4 expression in the saliva of systemic lupus erythematosus correlated with the serum vitamin D/25-hydroxyvitamin D: A cross-sectional study

Aim: This study aimed to examine the correlation between serum vitamin D (25-hydroxyvitamin D [25(OH)D]) and the transmembrane Toll-like receptor (TLR) 4 expression on CD11b+ cells in systemic lupus erythematosus (SLE) saliva. Materials and Methods: A cross-sectional study was conducted on 30 SLE patients who regularly visited to rheumatology clinic and met the following criteria: no systemic diseases, no smoking, no drinking and use of oral contraceptives, no steroid and immunosuppressant medications, no pregnancy, no wearing of dentures, and orthodontic appliances. The subject’s blood samples were taken for electrochemiluminescence immunoassay analyzer methods of examining 25(OH)D level. Full unstimulated whole saliva collection for the measurement of TLR4 expression. The descriptive demographic data, the chi-square, t test, and linear regression (95% confidence level) were used to analyze the association between blood 25(OH)D concentrations and immune cells expressing TLR4 in saliva CD11b+ cells. Results: SLE subjects had an average blood concentration of 25(OH)D of 9.9 ± 4.6 ng/mL. in saliva CD11b+ cells, TLR4 expression was 26.0 ± 20.9%. r = 0.473 and P < 0.05 indicated a correlation between the saliva CD11b+ cells expressing TLR4 and the serum level of 25(OH)D. Only 25(OH)D predicted TLR4 expression of the saliva CD11b+ cells. Conclusions: TLR4 expression of Saliva CD11b+ cells correlated with the concentrations of serum 25(OH)D in SLE. Hence, vitamin D/25(OH)D may control the immune response of SLE patients’ oral cavity.

ENAMPT/TLR4 inflammatory cascade activation is a key contributor to SLE Lung vasculitis and alveolar hemorrhage

RationaleEffective therapies to reduce the severity and high mortality of pulmonary vasculitis and diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus (SLE) is a serious unmet need. We explored whether biologic neutralization of eNAMPT (extracellular nicotinamide phosphoribosyl-transferase), a novel DAMP and Toll-like receptor 4 ligand, represents a viable therapeutic strategy in lupus vasculitis. MethodsSerum was collected from SLE subjects (n = 37) for eNAMPT protein measurements. In the preclinical pristane-induced murine model of lung vasculitis/hemorrhage, C57BL/6 J mice (n = 5–10/group) were treated with PBS, IgG (1 mg/kg), or the eNAMPT-neutralizing ALT-100 mAb (1 mg/kg, IP or subcutaneously (SQ). Lung injury evaluation (Day 10) included histology/immuno-histochemistry, BAL protein/cellularity, tissue biochemistry, RNA sequencing, and plasma biomarker assessment. ResultsSLE subjects showed highly significant increases in blood NAMPT mRNA expression and eNAMPT protein levels compared to healthy controls. Preclinical pristane-exposed mice studies showed significantly increased NAMPT lung tissue expression and increased plasma eNAMPT levels accompanied by marked increases in alveolar hemorrhage and lung inflammation (BAL protein, PMNs, activated monocytes). In contrast, ALT-100 mAb-treated mice showed significant attenuation of inflammatory lung injury, alveolar hemorrhage, BAL protein, tissue leukocytes, and plasma inflammatory cytokines (eNAMPT, IL-6, IL-8). Lung RNA sequencing showed pristane-induced activation of inflammatory genes/pathways including NFkB, cytokine/chemokine, IL-1β, and MMP signaling pathways, each rectified in ALT-100 mAb-treated mice. ConclusionsThese findings highlight the role of eNAMPT/TLR4-mediated inflammatory signaling in the pathobiology of SLE pulmonary vasculitis and alveolar hemorrhage. Biologic neutralization of this novel DAMP appears to serve as a viable strategy to reduce the severity of SLE lung vasculitis.

Anxiety and depression in patients with primary and secondary fibromyalgia in Bulgaria

Fibromyalgia (FM) is characterized by a chronic widespread pain, general fatigue, anxiety, depression, sleep disturbances and functional disorders. FM affects both women and men in 9:1 to 20:1 ratio. Osteoarthritis, systemic lupus erythematosus and other diseases have often been and continue to be associated with fibromyalgia. The incidence rate of secondary FM in SLE and OA patients is around 20%. The purpose of this clinical study is to analyze anxiety and depression in patients with primary and secondary fibromyalgia. In prospective study eighty-three patients with primary FM, 39 patients with FM and osteoarthritis (OA), 23 patients with FM and systemic lupus erythematosus (SLE), 27 patients with SLE and 36 healthy subjects were included. The present study compared chronic pain, anxiety and depression in patients with primary FM, patients with SLE, FM + OA, FM + SLE and healthy subjects. Based on the HADS clinical parameter, anxiety and depression are a statistically significant difference of the control group, as compared to patients with primary FM, FM + OA, FM + SLE (p&lt;0,05) and no difference in patients with SLE (p=0.77). There was no significant difference in HADS depression scores between the three groups of fibromyalgia patients. There was no significant difference in terms of the clinical parameter of depression between the SLE and FM + SLE groups. The comparison between the patient groups is important to evaluate the disease activity and the treatment to be recommended.

Peroxisome proliferator activated receptor-γ agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus

ObjectivesPremature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent...

MiRNA-binding site polymorphismin IL-15RA gene in rheumatoid arthritis and systemic lupus erythematosus: correlation with disease risk and clinical characteristics.

MiRSNPs may interfere with mRNA stability through effects on microRNAs (miRNAs)-mRNA interactions via direct changes in miRNA binding site or effect on the secondary structure of this region and changes in accessibility of this region to miRNAs. Studies have confirmed that an elevated level of interleukin-15 receptor alpha (IL-15RA) has an important role in the pathogenesis of systemic lupus erythematosus(SLE) andrheumatoid arthritis(RA). In the present study, for the first time, we aimed to evaluate the possible correlation between a miRSNP, rs2296135, in IL-15RA gene with the risk of SLE and RA. In this case-control study, 100 SLE patients, 100 RA patients, and 110 healthy participants were enrolled to assess rs2296135 genotypes with real-time PCR high-resolution melting method. According to our findings, AA genotype and A allele of rs2296135 were considerably associated with enhanced risk of RA (for AA genotype, OR = 2.29; 95% CI [1.06-5.02]; for A allele, OR = 1.65; 95% CI [1.10-2.48]). However, this common variant was not significantly correlated with SLE risk in population under study. Stratification analysis in the RA group verified that patients with the A allele had considerably higher serum concentrations of C-reactive protein (CRP) (P < 0.001). In SLE subjects, the frequency of arthritis (P: 0.021) and renal involvement (P: 0.025) in patients with A allele was significantly higher than in other SLE individuals. The current study proposes a substantial association between rs2296135 polymorphism in IL-15RA gene with augmented risk of RA and some clinical characteristics in RA and SLE patients.

The DNA sensors AIM2 and IFI16 are SLE autoantigens that bind neutrophil extracellular traps.

Nucleic acid binding proteins are frequently targeted as autoantigens in systemic lupus erythematosus (SLE) and other interferon (IFN)-linked rheumatic diseases. The AIM-like receptors (ALRs) are IFN-inducible innate sensors that form supramolecular assemblies along double-stranded (ds)DNA of various origins. Here, we investigate the ALR absent in melanoma 2 (AIM2) as a novel autoantigen in SLE, with similar properties to the established ALR autoantigen interferon-inducible protein 16 (IFI16). We examined neutrophil extracellular traps (NETs) as DNA scaffolds on which these antigens might interact in a pro-immune context. AIM2 autoantibodies were measured by immunoprecipitation in SLE and control subjects. Neutrophil extracellular traps were induced in control neutrophils and combined with purified ALR proteins in immunofluorescence and DNase protection assays. SLE renal tissues were examined for ALR-containing NETs by confocal microscopy. AIM2 autoantibodies were detected in 41/131 (31.3%) SLE patients and 2/49 (4.1%) controls. Our SLE cohort revealed a frequent co-occurrence of anti-AIM2, anti-IFI16, and anti-DNA antibodies, and higher clinical measures of disease activity in patients positive for antibodies against these ALRs. We found that both ALRs bind NETs in vitro and in SLE renal tissues. We demonstrate that ALR binding causes NETs to resist degradation by DNase I, suggesting a mechanism whereby extracellular ALR-NET interactions may promote sustained IFN signaling. Our work suggests that extracellular ALRs bind NETs, leading to DNase resistant nucleoprotein fibers that are targeted as autoantigens in SLE. These studies were funded by NIH R01 DE12354 (AR), P30 AR070254, R01 GM 129342 (JS), K23AR075898 (CM), K08AR077100 (BA), the Jerome L. Greene Foundation and the Rheumatology Research Foundation. Dr. Antiochos and Dr. Mecoli are Jerome L. Greene Scholars. The Hopkins Lupus Cohort is supported by NIH grant R01 AR069572. Confocal imaging performed at the Johns Hopkins Microscopy Facility was supported by NIH Grant S10 OD016374.

Association of a miRNA-binding site polymorphism in IL-16 gene with disease risk and clinical characteristics of rheumatoid arthritis and systemic lupus erythematosus.

/objectives. Single nucleotide polymorphisms (SNPs) located at the 3'-UTR region of the target genes of microRNAs (miRNAs) can dysregulate their expression via disrupting the binding site of miRNAs. Interleukin-16 (IL-16) is involved in the pathogenesis of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In the current study, we assessed the possible association between rs1131445 polymorphism in IL-16 gene with risk and clinical characteristics of RA and SLE in the Iranian population. In this case-control study, 120 patients with RA, 120 patients with SLE, and 120 unrelated healthy subjects were collected to estimate rs1131445 (T > C) polymorphism in IL-16 gene using real-time PCR high-resolution melting (HRM) method. Our results demonstrated considerable associations between TC genotype and C allele of rs1131445 with enhanced risk of RA (ORfor TC genotype = 3.01; 95%CI [1.667-5.526], P < 0.001; ORfor C allele = 1.96; 95%CI [1.314-2.941], P < 0.001). Besides, there was a marginal association between CC genotype and increased risk of RA (P: 0.031). However, there was an insignificant correlation between genotypes and allele frequencies of rs1131445 with incidence risk of SLE (P > 0.05). Moreover, stratification analysis indicated that the C allele in rs1131445 was linked with disease activity-associated laboratory parameters such as CRP and ESR in both RA and SLE patients, as well as the higher incidence of neurological symptoms in SLE subjects (P < 0.05). These results proposed a significant association between IL-16 polymorphism and augmented risk of RA and clinical characteristics of RA and SLE.

Peripheral biochemical parameters associated with neuroinflammation and depression in systemic lupus erythematosus subjects

Peripheral biochemical parameters associated with neuroinflammation and depression in systemic lupus erythematosus subjects

The Correlation between Allergic Diseases and Systemic Lupus Erythematosus

Background: The prevalence of autoimmune diseases and major chronic allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis are increasing in line with the occurrence of climate change. Allergy and systemic lupus erythematosus (SLE) are sometimes being linked since both are immune diseases involving gene-environment interactions. The purpose of this research is to investigate the correlation between allergic diseases and SLE. Method : This case-control study was performed on 39 SLE subjects from the Tittari Community and 39 non-SLE subjects aged 15-49 years old, from September until October 2021. All of them were females. The independent variable was allergic disease and the dependent variable was SLE. Partici­pants' characteristics and allergy data were collected through answering the online Score for Allergic Rhinitis (SFAR) questionnaire, then the results were processed with bivariate and multivariate analyses. Results : The correlation between allergic diseases and SLE was significant for atopic dermatitis but not for allergic rhinitis and asthma (p=0.018; p=0.352; p=0.151 respectively). The bivariate analysis revealed that the risk of SLE was 3.17 times higher in atopic dermatitis patients (OR=3.17; 95% CI=1.20-8.39; p=0.018). Furthermore, the multivariate analysis found that subjects with atopic dermatitis had the highest risk of SLE (OR= 3.18; 95% CI= 1.07-9.51; p=0.031). Conclusion: Among allergic diseases, atopic dermatitis was found to be significantly correlated with SLE, where the risk of SLE was raised as the number of atopic dermatitis increased. Keywords: systemic lupus erythematosus, allergic diseases, allergic rhinitis, asthma, atopic dermatitis Correspondence: Dewi Pratiwi. Department of Otorhinolaryngology Head and Neck Surgery, Faculty of Medicine, Universitas Sebelas Maret – Moewardi Hospital, Indonesia. Email: pratiwidewi81@staff.uns.ac.id. Phone: (0271) 664569. Indonesian Journal of Medicine (2022), 07(01): 19-27 https://doi.org/10.26911/theijmed.2022.07.01.03

Comparison of Short-Chain Fatty Acid (SCFA) and Interleukin-10 (IL-10) Levels in Patients with Systemic Lupus Erythematosus (SLE) Compared to Healthy Populations at RSUP Dr. Mohammad Hoesin Palembang

Background. Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease with various significant diseases, where SLE can affect the entire population in the world. This study aims to compare and analyze differences in the composition of the gut microbiota of SLE patients compared to healthy controls based on SCFA examination in Indonesia.&#x0D; Methods. The type of research conducted in this research is an analytical observational study with a case-control design. The research was conducted at Dr. RSUP. Mohammad Hoesin Palembang from October 2020 to October 2021. The sample in this study was divided into two groups, namely, the case group, and the control group. The case group was all SLE patients who met the inclusion criteria, while the control group was a healthy population who did a medical check-up at Dr. RSUP. Mohammad Hoesin Palembang. SCFA examination was carried out using Gas Chromatography-Mass Spectrometry (GCMS) from fecal samples.&#x0D; Results. The results showed that there were two groups of SCFA values, namely the normal group and the microbiota dysbiosis group where the SCFA value was low or less than 4. in the SLE and normal populations where there were 6 SLE subjects who had normal SCFA values or 37.5% and there were 10 SLE subjects who experienced microbiota dysbiosis. or 62.5%. In the healthy population group, all subjects had SCFA values that were included in the normal category, namely 16 subjects or 100%. Based on the severity of SLE using the SLEDAI MEX score, all SLE patients in the study were in the active or category flare where the SLEDAI MEX score was &gt; 5.&#x0D; Conclusion. Patients with microbiota dysbiosis tended to have an LES of 7,222 or 7 times greater than patients who did not have microbiota dysbiosis or had normal SCFA values.

MiR-301a-3p Advances IRAK1-Mediated Differentiation of Th17 Cells to Promote the Progression of Systemic Lupus Erythematosus via Targeting PELI1.

Systemic lupus erythematosus (SLE) is a common autoimmune disease with high incidence in females. The pathogenesis of SLE is complex, and healing SLE has become a serious challenge for clinical treatment. Aberrant expression of miR-301a-3p involves the progressions of multiple diseases, and some studies have indicated that increased miR-301a-3p could induce the inflammatory injury of some organs. However, the role and molecular mechanism of miR-301a-3p in SLE remain unclear. In this study, the miR-301a-3p levels in peripheral blood mononuclear cells (PBMCs) of the patients with SLE and health subjects were measured with qRT-PCR. The ELISA assay was used to investigate the effect of miR-301a-3p on the levels of inflammatory factors in PBMCs, and flow cytometry assays were used to observe the effect of miR-301a-3p on the levels of CD4+ T cells and Th17 cells in PBMCs. Moreover, TargetScan, dual-luciferase reporter assay, and western blot were used to reveal the downstream targets and regulation mechanism of miR-301a-3p in SLE. The results showed that miR-301a-3p was significantly upregulated in PBMCs of the SLE patients, and increased miR-301a-3p could boost the expression of IL-6, IL-17, and INF-γ in PBMCs and promote the differentiation of Th17 cells. It was found that PELI1 was a target of miR-301a-3p, and PELI1 upregulation could effectively reverse the effect of miR-301a-3p on PBMCs. Besides, this study also found that miR-301a-3p could promote the expression of IRAK1 to involve the progression of SLE via targeting PELI1. In conclusion, this study suggests that increased miR-301a-3p serves as a pathogenic factor in SLE to promote IRAK1-mediated differentiation of Th17 cells via targeting PELI1.

Hydroxychloroquine use is not associated with QTc length in a large cohort of SLE and RA patients

BackgroundHydroxychloroquine (HCQ) is a cornerstone therapy for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, reports of its use and subsequent fatal arrhythmias in patients with coronavirus disease 19 (COVID-19) have raised concern regarding its cardiovascular (CV) safety. Therefore, we examined the relationship between HCQ use and corrected QT (QTc) length in SLE and RA patients without clinical CV disease (CVD).MethodsSLE patients from the Columbia University Lupus Cohort registry (n = 352) and two RA cohorts (n = 178; ESCAPE-RA and RHYTHM-RA) with electrocardiograms (ECGs) collected as part of study data were analyzed. RA cohort participants were recruited from tertiary referral centers with additional referrals from community rheumatologists, while SLE subjects originated from the Columbia University Lupus Cohort. All patients met American College of Rheumatology (ACR) classification criteria for SLE or RA and lacked known CVD. The exposure of interest was HCQ use and main outcome measure was QTc length [continuous or categorical (≥ 440 ms and ≥ 500 ms)].ResultsOf the combined SLE and RA cohorts (n = 530), 70% were HCQ users and 44% had a QTc ≥ 440 ms. The adjusted mean QTc length was comparable between HCQ users vs non-users (438 ms vs 437 ms). In multivariable logistic models, HCQ use was not a significant predictor of a QTc ≥ 440 ms for the entire cohort (OR 0.77; 95% CI 0.48–1.23; p = 0.27). Importantly, a QTc ≥ 500 ms was inversely associated with HCQ use and not associated with arrhythmias or deaths. A significant interaction was found between HCQ use and use of anti-psychotics. Ultimately, the use of HCQ combined with any QTc prolonging medication as a group was associated with a QTc length (434 ms; 95% CI 430, 439) which was comparable to that of use of HCQ alone (433 ms; 95% CI 429-437).ConclusionIn a combined cohort of SLE and RA patients without clinical CVD, adjusted QTc length was comparable between HCQ and non-HCQ users, supporting its CV safety in patients with rheumatic diseases.

Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus

Increased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In lupus animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled clinical trial of tofacitinib in SLE subjects (ClinicalTrials.gov NCT02535689). In this study, 30 subjects are randomized to tofacitinib (5 mg twice daily) or placebo in 2:1 block. The primary outcome of this study is safety and tolerability of tofacitinib. The secondary outcomes include clinical response and mechanistic studies. The tofacitinib is found to be safe in SLE meeting study’s primary endpoint. We also show that tofacitinib improves cardiometabolic and immunologic parameters associated with the premature atherosclerosis in SLE. Tofacitinib improves high-density lipoprotein cholesterol levels (p = 0.0006, CI 95%: 4.12, 13.32) and particle number (p = 0.0008, CI 95%: 1.58, 5.33); lecithin: cholesterol acyltransferase concentration (p = 0.024, CI 95%: 1.1, −26.5), cholesterol efflux capacity (p = 0.08, CI 95%: −0.01, 0.24), improvements in arterial stiffness and endothelium-dependent vasorelaxation and decrease in type I IFN gene signature, low-density granulocytes and circulating NETs. Some of these improvements are more robust in subjects with STAT4 risk allele.