Development Of Systemic Lupus Erythematosus Research Articles

The dysregulation of mitochondrial homeostasis-related genes could be involved in the decrease of mtDNA copy number in systemic lupus erythematosus patients.

Systemic lupus erythematosus (SLE) is a chronic multifactorial autoimmune disease. It is now widely demonstrated that oxidative stress (OS) plays an important role in the modulation of the pathogenesis of this disease. Mitochondrial DNA (mtDNA) is highly vulnerable to OS and it is known a decrease of mtDNA copy number in SLE patients. However, to date, it has not been investigated if this decrease is associated with a dysregulation of mitochondrial homeostasis genes. Our aim is to evaluate the amount of mtDNA copy number and the expression of the genes more involved in the mitochondrial homeostasis pathways, in peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls. We analysed the amount of mtDNA in PBMCs of 72 SLE patients and 61 healthy controls by qPCR. Then, we investigated the expression variability of TFAM and SIRT1 (biogenesis), MFN1 and MFF (fusion/fission) and PRKN2 (mitophagy) genes in a subgroup of SLE patients and healthy controls. Interestingly, we have observed a highly significant decrease in mtDNA copies in SLE patients compared to healthy controls (P < 0.0001). In addition, we have shown that the expression levels of SIRT1, MFN1 and PRKN2 genes were significantly decreased in SLE patients with respect to healthy controls (P = 0.00001 for SIRT1, P = 0.0150 for MFN1 and P = 0.0009 for PRKN2). Lastly, we have reported a positive correlation between PRKN2 expression level and mtDNA copy number (P = 0.019, r = 0.475). In conclusion, our data confirm the impairment of mtDNA copy number in the disease and show for the first time a dysregulation of the mitochondrial homeostasis genes. These results could provide additional support to the important role of mitochondria in SLE development.

Association Study of 3-untranslated region Haplotype of Human leukocyte antigen-G Gene with Lupus.

Background: Human leukocyte antigen-G (HLA-G) is a pivotal protein involved in immune regulation and tolerance, while systemic lupus erythematosus (SLE) is a multifaceted autoimmune condition influenced by genetic and environmental factors. Research indicates that variations and mutations in HLA-G may impact SLE development. Objective: This study aimed to explore the relationship between polymorphisms in the 3'-untranslated region (UTR) of the HLA-G gene and SLE. Methods: DNA from 100 SLE patients and 100 controls was analyzed using polymerase chain reaction to amplify the target sequence. Allele and genotype frequencies were determined, and haplotypes were assessed using Haploview v.4.2 software, with linkage disequilibrium calculated. Results: Findings revealed that the +2960 Ins allele was significantly linked to SLE as a risk factor, with the Del allele showing a protective effect. In addition, the +3010C allele and +3187A allele were significantly associated with SLE at both allele and genotype levels. The +3142 GG homozygote was notably linked to SLE at the genotype level. Haplotype analysis identified UTR-2 haplotypes as risk factors for SLE, whereas the UTR-1 haplotype was protective, shedding light on genetic factors influencing SLE risk. Conclusion: This study underscores the importance of HLA-G gene 3'-UTR polymorphisms in SLE susceptibility, suggesting their potential as diagnostic or therapeutic targets.

Association between a single-nucleotide polymorphism of the angiotensin-converting enzyme gene and susceptibility to systemic lupus erythematosus in the Hainanese population of China.

The angiotensin-converting enzyme (ACE) gene plays a significant role in regulating immune responses and inflammatory processes, thus impacting the susceptibility to systemic lupus erythematosus (SLE). Understanding how single-nucleotide polymorphisms (SNPs) within the ACE gene contribute to the genetic susceptibility to SLE is essential for comprehending the disease's aetiology. Therefore, exploring this relationship in the Hainan region of China is crucial for gaining insights into the pathogenesis of SLE. This study comprised 428 participants, including 214 SLE patients and 214 healthy controls. Clinical data were gathered, and blood samples were collected. Genotyping of three SNPs (rs4459609, rs4309, rs1987692) within the ACE gene was performed using SNaPshot technology. The frequencies of alleles and genotypes of these three SNPs were compared between the SLE and control groups. Combining different genetic models and haplotype analysis, the correlation between ACE gene polymorphisms and SLE was investigated. Both study groups exhibited conformity with the Hardy-Weinberg genetic equilibrium (p>.05). Significant differences were observed in the genotype frequency distributions of ACE genes rs4459609, rs4309 and rs1987692 between the SLE and control groups (p=.009,.008,.032, respectively). The frequency of allele T at rs4309 was significantly higher in the SLE group than in the control group, correlating significantly with increased SLE risk (odds ratio [OR]=1.527, 95% confidence interval [CI]=1.147-2.035). Associations among ACE rs4459609, rs4309 and rs1987692 polymorphisms and increased susceptibility to SLE were found under co-dominant and dominant models (p<.05, with OR values and 95% CI greater than 1). Linkage disequilibrium was observed among rs4459609, rs4309 and rs1987692, and haplotype analysis revealed a significantly higher frequency of the CCA haplotype in the control group compared to the SLE group (p<.001). The ACA and ATA haplotypes showed significantly higher frequencies in the SLE group than in the control group (p=.014, p=.013, respectively). ACE gene polymorphisms are associated with the genetic susceptibility to SLE. The AC and AA genotypes at the rs4459609 locus, the TT genotype and T allele at the rs4309 locus and the AC and CC genotypes at the rs1987692 locus may serve as risk factors for the development of SLE.

Identifying the genetic association between common rheumatic diseases and vitiligo.

Although observational studies have suggested a correlation between vitiligo and rheumatic diseases, conclusive evidence supporting a causal relationship is still lacking. Therefore, this study aims to explore the potential causal relationship between vitiligo and rheumatic diseases. Using genome-wide association studies, we performed a two-sample Mendelian randomization (MR) analysis. In our analysis, the random-effects inverse variance weighted (IVW) method was predominantly employed, followed by several sensitivity analyses, which include heterogeneity, horizontal pleiotropy, outliers, and "leave-one-out" analyses. The genetically predicted vitiligo was associated with an increased risk of rheumatoid arthritis (RA) (OR, 1.47; 95% confidence interval [CI], 1.29-1.68; p<0.001), and systemic lupus erythematosus (SLE) (OR, 1.22; 95% CI, 1.06-1.39; p=0.005). The causal associations were supported by sensitivity analyses. In Sjögren's syndrome and ankylosing spondylitis, no causal relationship with vitiligo was found in the study. Our MR results support the causal effect that vitiligo leads to a higher risk of RA and SLE. Individuals with vitiligo should be vigilant for the potential development of RA and SLE. Managing and addressing this potential requires regular monitoring.

Deletion of the Mitochondrial Membrane Protein Fam210b Is Associated with the Development of Systemic Lupus Erythematosus.

Mitochondrial dysfunction has been increasingly recognized as a trigger for systemic lupus erythematosus (SLE). Recent bioinformatics studies have suggested Fam210b as a significant candidate for the classification and therapeutic targeting of SLE. To experimentally prove the role of Fam210b in SLE, we constructed Fam210b knockout (Fam210b-/-) mice using the CRISPR-Cas9 method. We found that approximately 15.68% of Fam210b-/- mice spontaneously developed lupus-like autoimmunity, which was characterized by skin ulcerations, splenomegaly, and an increase in anti-double-stranded DNA (anti-dsDNA) IgG antibodies and anti-nuclear antibodies(ANA). Single-cell sequencing showed that Fam210b was mainly expressed in erythroid cells. Critically, the knockout of Fam210b resulted in abnormal erythrocyte differentiation and development in the spleens of mice. Concurrently, the spleens exhibited an increased number of CD71+ erythroid cells, along with elevated levels of reactive oxygen species (ROS) in the erythrocytes. The co-culture of CD71+ erythroid cells and lymphocytes resulted in lymphocyte activation and promoted dsDNA and IgG production. In summary, Fam210b knockout leads to a low probability of lupus-like symptoms in mice through the overproduction of ROS in CD71+ erythroid cells. Thus, Fam210b reduction may serve as a novel key marker that triggers the development of SLE.

Inhibition of GRK2 ameliorates the pristane-induced mouse SLE model by suppressing plasma cells differentiation

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by diverse clinical manifestations and organ damage. Despite its elusive etiology, dysregulated subsets and functions of B cells are pivotal in SLE pathogenesis. Peoniflorin-6′-O-benzene sulfonate (CP-25), an esterification modification of Paeoniflorin, exhibits potent anti-inflammatory and immunomodulatory properties in autoimmune diseases (AID). However, the involvement of CP-25 and its target, GRK2, in SLE development has not been explored. In this study, we demonstrate that both genetic deficiency and pharmacological inhibition of GRK2 attenuate autoantibodies production, reduce systemic inflammation, and mitigate histopathological alterations in the spleen and kidney in the pristane-induced mouse SLE model. Importantly, our findings highlight that both genetic deficiency and pharmacological inhibition of GRK2 suppress plasma cells generation and restore dysregulated B-cell subsets by modulating two crucial transcription factors, Blimp1 and IRF4. Collectively, targeting GRK2 with CP-25 emerges as a promising therapeutic approach for SLE.

Elucidating the function of STING in systemic lupus erythematosus through the STING Goldenticket mouse mutant

The complexity of systemic lupus erythematosus (SLE) arises from intricate genetic and environmental interactions, with STING playing a pivotal role. This study aims to comprehend the function of STING using the pristane-induced lupus (PIL) model in Sting missense mutant mice (Goldenticket or StingGt), which contrasts with previous research using Sting knockout mice. Investigating two-month-old StingGt mice over six months post-PIL induction, we observed a profound reduction in autoimmune markers, including antinuclear and anti-dsDNA antibodies, germinal center B cells, and plasma cells, compared to their wild-type counterparts. A pivotal finding was the marked decrease in IL-17-producing T cells. Notably, the severity of lupus nephritis and pulmonary hemorrhages was significantly diminished in StingGt mice. These findings demonstrate that different genetic approaches to interfere with STING signaling can lead to contrasting outcomes in SLE pathogenesis, which highlights the need for a nuanced understanding of the role of STING in drug development for SLE. In summary, the loss of Sting function in Goldenticket mutant mice rescued autoimmune phenotypes in PIL. This study reveals the critical nature of STING in SLE, suggesting that the method of STING modulation significantly influences disease phenotypes and should be a key consideration in developing targeted therapies.

Systemic lupus erythematosus therapeutic strategy: From immunotherapy to gut microbiota modulation.

Systemic lupus erythematosus (SLE) is characterized by a systemic dysfunction of the innate and adaptive immune systems, leading to an attack on healthy tissues of the body. During the development of SLE, pathogenic features, such as the formation of autoantibodies to self-nuclear antigens, caused tissue damage including necrosis and fibrosis, with an increased expression of type Ⅰ interferon (IFN) regulated genes. Treatment of lupus with immunosuppressants and glucocorticoids, which are used as the standard therapy, is not effective enough and causes side effects. As an alternative, more effective immunotherapies have been developed, including monoclonal and bispecific antibodies that target B cells, T cells, co-stimulatory molecules, cytokines or their receptors, and signaling molecules. Encouraging results have been observed in clinical trials with some of these therapies. Furthermore, a chimeric antigen receptor T cells (CAR-T) therapy has emerged as the most effective, safe, and promising treatment option for SLE, as demonstrated by successful pilot studies. Additionally, emerging evidence suggests that gut microbiota dysbiosis may play a significant role in the severity of SLE, and the use of methods to normalize the gut microbiota, particularly fecal microbiota transplantation (FMT), opens up new opportunities for effective treatment of SLE.

Genes, Antibodies, and Cytokines in Systemic Lupus Erythematosus: Update of Potential Biomarkers

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown aetiology, with the broad range of antibodies affecting various organs and tissues, leading to rapid disability and even to lethal outcome. Our objective was to make an analysis of the results of relevant global studies about genetic mutations, spectrum of antibodies and cytokines involved in the pathogenesis of SLE. The search was conducted in PubMed and Google Scholar platforms using keywords “systemic lupus erythematosus”, “genetic mutations”, “autoantibodies”, “cytokine production”, “sequencing”, “NGS" and "exome". Several genes were found to be involved in the pathogenesis of SLE, the majority of which were associated with B- and T-cell abnormal activation. The results of different studies revealed an association of active SLE with the increase in specific circulating autoantibodies. Based on the results of the current review, a preliminary list of autoantibodies, genes and cytokines associated with the development of SLE was prepared. Future directions will include the assessment of association of genes, antibodies and cytokines in SLE patients from the local Kazakh population, and the development of genetic-immunologic panel for the early diagnosis of this disease.

Causal association between systemic lupus erythematosus and primary biliary cholangitis: A bidirectional Mendelian randomization study.

An association has been observed between systemic lupus erythematosus (SLE) and primary biliary cholangitis (PBC) in observational studies, however, the exact causal link remains unclear. We aim to evaluate the causal relationships between SLE and PBC through bidirectional Mendelian randomization (MR). Single-nucleotide polymorphisms (SNPs) were selected as instrumental variables from publicly accessible genome-wide association studies (GWAS) in European populations. The PBC and SLE GWAS data were obtained from the MRC IEU Open GWAS database, consisting of 24,510 and 14,267 samples, respectively. After a series of quality control and outlier removal, inverse variance weighted was used as the primary approach to evaluate the causal association between SLE and PBC. The horizontal pleiotropy and heterogeneity were examined by the MR-Egger intercept test and Cochran Q value, respectively. Seven SNPs were included to examine the causal effect of SLE on PBC. Genetically predicted SLE may increase the risk of PBC development, with an odds ratio (OR) of 1.324 (95% confidence interval [CI] 1.220 ∼ 1.437, P ˂ .001). Twenty SNPs were included to explore the causal effect of PBC on SLE. Genetically predicted PBC may increase the risk of SLE development, with an OR of 1.414 (95% CI 1.323 ∼ 1.511, P ˂ .001). Horizontal pleiotropy and heterogeneity were absent (P > .05) among SNPs. The robustness of our results was further enhanced by using the leave-one-out method. Our research has provided new insights into SLE and PBC, indicating bidirectional causal associations between the 2 diseases. These findings offer valuable contributions to future clinical studies.

#2600 Idiopathic full-house non-lupus nephropathy

Abstract Background and Aims A full-house pattern at immunofluorescence (IF) in kidney biopsies is usually associated with Lupus Nephritis (LN). However, it can be also secondary to other causes, such as infections, or it can idiopathic, without a defined origin. Idiopathic Full House non-lupus Nephropathy (iFH-N) represents a rare entity previously identified in small cohorts of patients, with different clinical features and outcomes. A limited number of the described cases developed overt systemic lupus erythematosus (SLE) during follow up, while renal outcome varied across different studies. A retrospective observational study aimed at evaluating clinical presentation and outcomes of patients with iFH-N in a Tertiary Center has been performed. Long-term renal function and development of overt SLE have been considered as main outcomes of the study. Method All native kidney biopsies performed from January 2012 to December 2022 in our Institution were considered. Full-house pattern was defined as simultaneous positivity for IgG, IgM, IgA, C3 and C1q staining at IF. Inclusion criteria were: age ≥18, full-house pattern at kidney biopsy, patients not meeting criteria for SLE diagnosis according to American College of Rheumatology (ACR) 1997 classification or Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria. Exclusion criteria: diagnosis of SLE, secondary causes of full-house pattern at kidney biopsy. We considered histological, clinical and laboratory features, performed therapies, renal function and SLE development during follow up. Results In the considered period, 2110 patients underwent a native kidney biopsy at our Institution. Of these, 91 patients had a histological finding of full-house nephropathy and were initially included for further evaluation. Of the 91 patients, 84 had received a diagnosis of SLE and were excluded, while 7 did not meet the criteria for a diagnosis of SLE. Two of these 7 were further excluded, having a full house pattern secondary to other conditions. Five patients were finally labelled as iFH-N. At kidney biopsy, all 5 included subjects had a Membranous Nephropathy, with extracapillary proliferation in 2 cases. They were all females, 4 Caucasians (80%), 1 Black (20%). At presentation, mean age was 28.2 years (range 21–40). All had impairment of kidney function, 2 of 5 had a full-blown nephrotic syndrome, 3 of 5 a nephrotic range proteinuria. Mean serum creatinine was 2.1 mg/dl (SD± 0.47), mean eGFR 35.2 ml/min/1.73 m2 (SD ±11), mean proteinuria 7.1 gr/24 h (SD ±3.3). Antinuclear antibodies (ANA) were negative in 4 of 5 patients; anti-dsDNA, anti-extractable nuclear antigens (ENAs) and antiphospholipid antibodies were negative in all subjects; slightly low C3 was present in 3 of 5 subjects. All patients received immunosuppressive therapy, including high dose intravenous (iv) steroids in association with cyclophosphamide (CYC) or mycophenolate mofetil, or Intensified B Cell Depletion Protocol (i.e. iv steroids + CYC and Rituximab). Mean follow-up from the time of kidney biopsy was 7.4 year (SD ± 2.4) (range 3–10 years). During follow up, 4 patients (80%) developed end stage renal disease (ESRD) needing renal replacement therapy, 3 of them within 24 months after presentation. The two patients with crescents had a severe prognosis, starting dialysis within 10 months after presentation. The fifth patient developed chronic kidney disease stage 4. One patient formally developed an ACR negative, SLICC positive SLE two years after presentation, with new positivity for ANA and anti-dsDNA antibodies at high titer and low C3, in addition to renal involvement. Conclusion All patients with iFH-N had similar presentation, being all young females, with a Membranous Nephropathy, nephrotic proteinuria and impairment of kidney function. They all had an aggressive form of kidney disease, refractory to different regimens of immunosuppression and with poor long-term renal outcome. Only one case developed SLE on the long term, although without systemic signs. The relationship between idiopathic full-house nephropathy and SLE remains controversial.

Lupus progression deteriorates oogenesis quality in MRL/lpr mice.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the activation of the immune response against self antigens. Numerous reproductive complications, including reduced birth rate and complications for the mother and the fetus during pregnancy, have been observed in women with SLE. In the present study, we aimed to investigate the effect of SLE development on oocyte meiosis in lupus-prone mice. Lupus-prone MRL/lpr mice were used for the experiments: disease-free (4weeks of age) and sick (20weeks of age, virgin and postpartum). The immune response was monitored by flow cytometry, ELISpot, ELISA, and histology. Oocytes were analyzed by fluorescence microscopy based on chromatin, tubulin, and actin structures. The lupus-prone MRL/lpr mice developed age-dependent symptoms of SLE with increased levels of various autoantibodies, proteinuria, and renal infiltrates and a tendency for the immune response to worsen with changes in cell populations and the cytokine profile. The number and quality of oocytes were also affected, and the successful pregnancy rate of MRL/lpr mice was limited to only 60%. Isolated oocytes showed severe structural changes in all studied groups. Systemic alterations in immune homeostasis in SLE affect the quality of developing oocytes, which is evident from a young age. The data obtained is in line with the trend of reduced fertility in lupus-prone MRL/lpr mice. The phenomenon can be explained by changes in the microenvironment of the relevant organs and close connection between ovulation and inflammatory processes.

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.

Methyl-supplemented nutrition delays the development of autoimmune disease in pristane-induced murine lupus.

The aetiology and progression of systemic lupus erythematosus (SLE) resulted from a complex sequence of events generated both from genetic and epigenetic processes. In the current research, the effect of methyl-supplemented nutrition on the development of SLE was studied in the pristane-induced mouse model of the disease. The results clearly demonstrated decreased anti-dsDNA antibody and proteinuria levels, modulation of cytokines and protected renal structures in the group of treated mice. An additional increase in the DNA methylation of mouse B lymphocytes was also observed. The beneficial effect of the diet is due to the methyl-containing micronutrients with possible anti-inflammatory and immunomodulating effects on cell proliferation and gene expression. Since these components are responsible for maintaining the physiological methylation level of DNA, the results point to the central role of methylation processes in environmentally triggered lupus. As nutrition represents one of the major epigenetic factors, these micronutrients may be considered novel agents with significant therapeutic outcomes.

Serum levels of CXCL5 are decreased and correlate with circulating platelet counts in systemic lupus erythematosus.

To identify disease-specific serum chemokine profiles and potential anti-inflammatory chemokines in three rheumatic diseases. The discovery cohort included 18 patients with rheumatoid arthritis (RA), 20 patients with primary Sjögren's syndrome (pSS), 24 patients with systemic lupus erythematosus (SLE) and 28 healthy subjects. Findings from the discovery cohort were validated in two replication cohorts, consisting of 23 patients with SLE matched with 23 healthy subjects and 62 patients with SLE, 16 patients with ANCA-associated vasculitis (AAV), and 32 healthy controls, respectively. Serum levels of chemokines were determined using multiplex assay or ELISA. In the discovery cohort, serum levels of multiple chemokines were increased in one or more diseases in comparison to healthy subjects, including CCL2, CCL20, CXCL9, CXCL10, and CXCL11 in SLE, CCL2, CCL4, and CXCL11 in pSS, and CCL2, CCL4, and CXCL9 in RA. Notably, serum levels of CCL3 (p = .0003) and CXCL5 (p = .0003) were decreased in SLE. The SLE-specific decrease in CXCL5 serum levels was confirmed in the two replication cohorts, with p = .0034 and p = .0006, respectively. Moreover, a positive correlation between serum levels of CXCL5 and circulating platelet counts (R = .71, p = .00018) in SLE observed in the discovery cohort was confirmed in both replication cohorts (R = .52, p = .011 and R = .49, p = .00005, respectively). In the present study, we demonstrate that serum levels of CXCL5 are decreased in patients with SLE and positively correlated with circulating platelet count. These findings suggest that platelet-associated CXCL5 is presumably involved in the development of SLE.

Large-scale DNA sequencing identifies rare variants associated with Systemic Lupus Erythematosus susceptibility in known risk genes

The identification of rare genetic variants associated to Systemic Lupus Erythematosus (SLE) could also help to understand the pathogenic mechanisms at the basis of the disease. In this study we have analyzed a cohort of 200 Italian SLE patients in order to explore the rare protein-coding variants in five genes (TNFAIP3, STAT4, IL10, TRAF3IP2, and HCP5) already investigated for commons variants found associated in our previous studies.Genomic DNA of 200 SLE patients was sequenced by whole exome sequencing. The identified variants were filtered by frequency and evaluated by in silico predictions. Allelic association analysis was performed with standard Fisher’s exact test.Introducing a cutoff at MAF < 0.01, a total of 19 rare variants were identified. Seven of these variants were ultra-rare (MAF < 0.001) and six were absent in the GnomAD database. For TNFAIP3 gene, the variant c.A1939C was observed in 4 SLE patients and it is located in a region enriched in phosphorylation sites and affects the predict affinity of specific kinases. In TRAF3IP2 gene, we observed 5 different rare variants, including the novel variant c.G410A, located in the region that mediates interaction with TRAF6, and therefore a possible risk factor for SLE development. In STAT4 gene, we identified 6 different rare variants. Among these, three missense variants decrease the stability of this protein. Moreover, 3 novel rare variants were detected in 3 SLE patients. In particular, c.A767T variant was predicted as damaging by six prediction tools.Concluding, we have observed that even in genes whose common variability is associated with SLE susceptibility, it is possible to identify rare variants that could have a strong effect in the disease development and could therefore allow a better understanding of the functional domain involved.

Role of some Immunological and non-Immunological Parameters in Prognosis and diagnosis of Systemic lupus erythematosus in Iraqi women patients

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody's presence in the circulation and involvement of many systems. The current study aims to study the role of some immunological and non-immunological parameters in SLE development and to illustrate the correlations between these parameters. The current study included 50 blood samples collected from SLE patients and apparently healthy control. The methods of work included Complete Blood Count (CBC) analysis to assess blood components, you mean to analyse Hb, WBC, ESR, ELISA technique to measure serum levels of TLR-7, IL-17, and TNF-γ, antinuclear antibody test (ANA) and double-strand DNA antibody (anti ds DNA). The study results showed a significant increase in serum levels of each WBC (p&lt; 0.005), ESR (p&lt; 0.001), IL17(p&lt; 0.004), TLR7(p&lt; 0.005), IFN-γ (p&lt; 0.001), ANA (p&lt; 0.001), and anti dsDNA (p&lt; 0.001) in SLE patients compared to apparently healthy control but the Hb is decreasing level was low in the SLE patients compared with control. In conclusion, the low hemoglobin, WBC, and ESR are non-specific parameters associated with SLE pathogenesis. ANA, Anti-ds-DNA as excellent biomarkers for the diagnosis of SLE and serum level of TLR-7, TNF-γ, and IL-17 were evaluated in SLE patients compared to healthy people and they may be suggested as a prognostic tool in SLE patients.

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.

Epstein-Barr virus infection as potential indicator of the occurrence and clinical presentation of systemic lupus erythematosus.

The relationship between Systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) infection has been suggested for decades, but the underlying mechanism of the EBV influence on SLE development remains to be elucidated. The goals of this research, which included 103 SLE patients and 99 controls, were to investigate the association of the parameters of EBV infection and SLE, to explore whether pooled demographic, clinical and EBV markers achieve a more significant effect on SLE development than each of them individually, and to evaluate EBV nuclear antigen 1 (EBNA1) and latent membrane protein 1 (LMP1) gene polymorphisms in isolates from SLE patients. Comprehensive results related to serological, molecular and sequence markers of EBV infection in SLE patients demonstrated even 24 times higher possibility of having SLE if there is the presence of anti-EBV-EA(D) (early antigen) IgG antibodies (OR=24.086 95%CI OR=2.86-216.07, p=0.004). There was the same distribution of glucocorticoids (p=0.130), antimalarials (p=0.213), and immunosuppressives (p=0.712) in anti-EBV-EA(D) IgG positive and negative SLE patients. Further, higher anti-EBV-EA(D) IgG antibodies titers were identified as independent factors associated with lymphopenia, hematological SLE manifestation (OR=1.041, 95%CI OR=1.01-1.08, p=0.025, while a higher titer of anti-CA (viral capsid antigen) IgG antibodies (OR=1.015, 95%CI OR=1.01-1.03, p=0.019) and positive RF (rheumatoid factors) (OR=4.871, 95%CI OR=1.52-15.61, p=0.008) were identified as independent factors associated with alopecia within SLE. Finally, novel data on EBV EBNA1 and LMP1 gene polymorphisms in lupus are reported. The results support further investigation targeting EBV as a prognostic marker and therapeutic goal for lupus.

Gut microbiota in systemic lupus erythematosus pathogenesis: an in-depth view of mechanisms inside

Systemic lupus erythematosus (SLE), an autoimmune disease that is known to be prototypic, brings systemic influence via abnormal production of autoantibodies targeting nuclear acid, possesses highly sophisticated pathogenesis related to genetic and environmental factors. In current studies, gut microbiota draws increasing attention from researchers as it is considered to trigger local and systemic immune responses. Researchers have detected a wide range of alterations happen in SLE cases and revealed a series of potential mechanisms of how microbiome and metabolites are involved in the development and progression of SLE: translocation of pathobionts out of their normal niches; molecular mimicry inducing cross-activity to initiate autoimmune response; and epitope spreading to widen the target of autoantibodies. Based on the understanding of the microenvironment, treatments aiming at adjusting gut microbiota are proposed, including but not limited to the usage of probiotics or prebiotics, narrow-spectrum antibiotics or phages, dietary management and faecal microbiota transplantation. In this article, research progress showing the connection of gut microbiome with SLE and potential mechanisms as well as suggesting more efficient therapeutic strategies for SLE are reviewed. Although more detailed pathogenesis mechanisms and theories of treatments remain unclear while integration of courses along with advanced techniques are required to reveal the complicated connection shown in clinical trials, research in this territory still shows a promising prospect.