Factor In Systemic Lupus Erythematosus Research Articles

IRF5 Variants Are Risk Factors for Systemic Lupus Erythematosus in Two Mexican Populations.

Interferon regulatory factor 5 ( IRF5 ) is one of the pivotal genes implicated in systemic lupus erythematosus (SLE) among diverse ethnic groups, including Europeans, Asians, Hispanics, and Africans. Notably, its significance appears particularly pronounced among Hispanic populations. Previous studies have identified several single-nucleotide variants within IRF5 , such as rs2004640G/T, rs2070197T/C, and rs10954213G/A, as associated with susceptibility to SLE among patients from Mexico City. However, the population of Yucatan, located in the Southeast of Mexico and characterized by a greater Amerindian genetic component, remains largely unexplored in this regard. Our study aimed to replicate the observed association between IRF5 variants and susceptibility to SLE among patients from Central Mexico and Yucatan. Furthermore, we investigated the impact of IRF5 rs59110799G/T, a variant that has not been previously studied in SLE individuals. Our study included 204 SLE patients and 160 controls from Central Mexico, as well as 184 SLE patients and 184 controls from Yucatan. All participants were females 18 years and older. We employed a TaqMan assay to detect the presence of the following single-nucleotide variants: rs2004640G/T, rs2070197T/C, rs10954213G/A, and rs59110799G/T. Furthermore, we utilized 2 distinct web tools and databases to predict the potential functional implications of IRF5 variants. In SLE patients from Central Mexico, several IRF5 alleles showed significant associations with the disease following adjustment by the Bonferroni test: the rs2070197C allele (odds ratio [OR], 2.08), the rs10954213A allele (OR, 1.59), and the rs59110799G allele (OR, 1.71). Conversely, among patients from Yucatan, the following alleles showed associations: rs2004640T (OR, 1.51), rs2070197C (OR, 1.62), rs10954213A (OR, 1.67), and rs59110799G (OR, 1.44). Our findings highlight genetic variations between Mexican populations and emphasize the role of IRF5 as a risk factor in SLE patients from both Central Mexico and Yucatan.

Neoself-antigens are the primary target for autoreactive T cells in human lupus

Major histocompatibility complex class II (MHC-II) is the most significant genetic risk factor for systemic lupus erythematosus (SLE), but the nature of the self-antigens that trigger autoimmunity remains unclear. Unusual self-antigens, termed neoself-antigens, are presented on MHC-II in the absence of the invariant chain essential for peptide presentation. Here, we demonstrate that neoself-antigens are the primary target for autoreactive Tcells clonally expanded in SLE. When neoself-antigen presentation was induced by deleting the invariant chain in adult mice, neoself-reactive Tcells were clonally expanded, leading to the development of lupus-like disease. Furthermore, we found that neoself-reactive CD4+ Tcells were significantly expanded in SLE patients. A high frequency of Epstein-Barr virus reactivation is a risk factor for SLE. Neoself-reactive lupus Tcells were activated by Epstein-Barr-virus-reactivated cells through downregulation of the invariant chain. Together, our findings imply that neoself-antigen presentation by MHC-II plays a crucial role in the pathogenesis of SLE.

Identification of ENTPD1 as a novel biomarker linking allergic rhinitis and systemic lupus erythematosus

Several studies reveal that allergic rhinitis (AR) is a significant risk factor of systemic lupus erythematosus (SLE). However, studies investigating the common pathogenesis linking AR and SLE are lacking. Our study aims to search for the shared biomarkers and mechanisms that may provide new therapeutic targets for preventing AR from developing SLE. GSE50223 for AR and GSE103760 for SLE were downloaded from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DEGs). The Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore the functions of shared DEGs. Hub genes were screened by cytoHubba (a plugin of Cytoscape) and validated in another two datasets. Gene set enrichment analysis (GSEA) and single-sample Gene set enrichment analysis (ssGSEA) algorithm were applied to understand the functions of hub gene. ENTPD1 was validated as a hub gene between AR and SLE. GSEA results revealed that ENTPD1 was associated with KRAS_SIGNALING_UP pathway in AR and related to HYPOXIA, TGF_BETA_SIGNALING and TNFA_SIGNALING_VIA_NFKB pathways in SLE. The expression of ENTPD1 was positively correlated with activated CD8 T cell in both diseases. Thus, ENTPD1 may be a novel therapeutic target for preventing AR from developing SLE.

Proposal of a novel cardiovascular risk prediction score in lupus nephritis.

Patients with systemic lupus erythematosus are prone to develop cardiovascular disease (CVD), and have increased morbidity and mortality. We conducted a retrospective analysis on lupus nephritis patients to assess the occurrence and predictors of major adverse cardiovascular events (MACE). Data were collected from patients who underwent kidney biopsy between 2005 and 2020. Statistical analysis was performed to unveil correlations. 91 patients were analyzed in this period, with a mean age of 37.3 ± 12.3 years and 86% being female. The mean follow-up time was 62 ± 48 months. 15.38% of the patients underwent at least one MACE. Two patients deceased of CVD. Increased age (35.81 ± 11.14 vs 45.5 ± 15.11 years, p=0.012) entailed a higher occurrence of MACEs. Neutrophil count (5.15 ± 2.83 vs 7.3 ± 2.99 Giga/L, p=0.001) was higher, whereas diastolic blood pressure (DBP) was lower (89.51 ± 10.96 vs 78.43 ± 6.9 mmHg, p<0.001) at the time of the biopsy in patients with MACE. Age, neutrophil count, and DBP proved to be independent predictors of MACEs. We propose a new model (CANDE - Cardiovascular risk based on Age, Neutrophil count, and Diastolic blood pressure Estimation score) calculated from these variables, which predicts the probability of MACE occurrence. This study underscores the importance of actively screening for cardiovascular risks in this vulnerable patient population. Age, neutrophil count, and diastolic blood pressure have been established as independent risk factors for MACE in lupus nephritis. The CANDE score derived from these parameters may serve as a prompt, cost-effective, and easily accessible estimation tool for assessing the likelihood of major adverse cardiovascular risk. These findings emphasize the necessity for comprehensive management strategies addressing both immune dysregulation and cardiovascular risk factors in systemic lupus erythematosus to mitigate adverse outcomes.

Dry eye disease in systemic lupus erythematosus: a cross sectional study.

To explore ocular surface manifestations of dry eye disease (DED) and its influencing factors in systemic lupus erythematosus (SLE) patients. Ophthalmological examinations were conducted in SLE patients (n=43) and controls (n=41), including Ocular Surface Disease Index (OSDI), objective scatter index (OSI), tear meniscus height (TMH), lipid layer thickness (LLT), non-invasive Keratograph tear breakup time (NIKBUT), corneal fluorescein score (CFS), Schirmer I test. DED was diagnosed according to the Tear Film and Ocular Surface Society Dry Eye Workshop II Criteria. SLE patients were further divided into DED group and non-DED group, the disease activity, clinical manifestations and laboratory investigations were compared between the two groups. The disease activity was evaluated by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K). Receiver operative characteristic (ROC) curve and multiple-factor binary logistic regression were performed. SLE patients showed higher OSDI [9.1 (2.8-15.9) vs 6.3 (2.2-7.5), P=0.035], higher OSI [1.67 (1.09-2.60) vs 0.96 (0.87-1.60), P=0.001], higher CFS [1 (0-2) vs 0 (0-1), P=0.001], lower LLT [65 (42-100) vs 100 (79.5-100), P=0.010], and lower NIKBUT [8.03 (4.02-9.73) vs 9.67 (5.26-12.71), P=0.030] than controls. The 32.6% of SLE patients had DED, which was higher than 12.2% of healthy controls. DED group showed higher SLEDAI-2K score [9.7±6.1 vs 5.4±3.4, P=0.025], higher anti-cardiolipin antibody (ACL) [8.7 (3.5-13.2) vs 3.6 (2.0-6.9), P=0.035], and higher proportion of patients with cutaneous eruption [42.9% vs 6.9%, P=0.015] than non-DED group. According to multiple-factor binary logistic regression analysis, the SLEDAI-2K score (OR=1.194, P=0.041) and cutaneous eruption (OR=7.094, P=0.045) could be consider as risk factors for DED in SLE patients. The ROC curve of the combined factors including age, disease duration, SLEDAI-2K score, ACL, and cutaneous eruption was analyzed, with a sensitivity of 0.786, a specificity of 0.793, and an area under curve of 0.820. Ocular surface affection is frequent in SLE patients, and patients with high disease activity and cutaneous eruption show increased risk of DED.

Incidence and risk factors of systemic lupus erythematosus in patients with primary immune thrombocytopenia: a systematic review and meta-analysis.

Immune disorders and autoantibodies has been noted in both primary immune thrombocytopenia (ITP) and systemic lupus erythematosus (SLE). Whether the two disorders are correlated is unclear. The lack of evidence on the incidence of and risk factors for SLE in primary ITP patients poses a challenge for prediction in clinical practice. Therefore, we conducted this study. The protocol was registered with PROSPERO (CRD42023403665). Web of Science, Cochrane, PubMed, and EMBASE were searched for articles published from inception to 30 September 2023 on patients who were first diagnosed with primary ITP and subsequently developed into SLE. Furthermore, the risk factors were analyzed. Study quality was estimated using the Newcastle-Ottawa Scale. The statistical process was implemented using the R language. This systematic review included eight articles. The incidence of SLE during the follow-up after ITP diagnosis was 2.7% (95% CI [1.3-4.4%]), with an incidence of 4.6% (95% CI [1.6-8.6%]) in females and 0 (95% CI [0.00-0.4%]) in males. Older age (OR = 6.31; 95% CI [1.11-34.91]), positive antinuclear antibody (ANA) (OR = 6.64; 95% CI [1.40-31.50]), hypocomplementemia (OR = 8.33; 95% CI [1.62-42.91]), chronic ITP (OR = 24.67; 95% CI [3.14-100.00]), organ bleeding (OR = 13.67; 95% CI [2.44-76.69]), and female (OR = 20.50; 95% CI [4.94-84.90]) were risk factors for subsequent SLE in ITP patients. Patients with primary ITP are at higher risk of SLE. Specific follow-up and prevention strategies should be tailored especially for older females with positive ANA, hypocomplementemia, or chronic ITP. In subsequent studies, we need to further investigate the risk factors and try to construct corresponding risk prediction models to develop specific prediction strategies for SLE.

Human herpesvirus type 6 in patients with systemic lupus erythematosus.

Infectious agents are considered one of the possible etiological factors of systemic lupus erythematosus (SLE). It has been suggested that human herpesvirus type 6 (HHV-6) may trigger autoimmune disorders, but few studies have been conducted on the relationship between this virus and autoimmune diseases, especially SLE. The present study aimed to compare the frequency of HHV-6 infection between SLE patients and healthy individuals. Serum samples were collected from 60 healthy people and 60 SLE patients referred to the rheumatology clinic of Shahid-Beheshti Hospital, Kashan, Iran, from January 2020 to January 2021. The following data were collected from the medical records of patients: sex; age; duration of disease; SLE clinical manifestations; and disease activity. After the extraction of viral DNA from samples, a nested polymerase chain reaction (PCR) test was performed to detect HHV-6. HHV-6 was detected in 12 SLE patients (20%) and in 8 healthy individuals (13.3%). A significant correlation was not obtained between SLE and the presence of HHV-6 (P = 0.09). There was no correlation between musculoskeletal involvements, skin lesions, renal manifestations, and hematological manifestations with the presence of HHV-6 (P>0.05). HHV-6 was detected more frequently in patients with active lupus than in patients with quiescent disease, but this difference was not significant (P=0.08). Although patients with SLE had a higher prevalence of HHV-6 compared with healthy people, there is no strong link between HHV-6 infection and SLE. Future research is necessary because this data does not support the hypothesis that human herpesvirus 6 plays a role in the pathogenesis of SLE.

Antinuclear antibody–associated autoimmune cytopenia in childhood is a risk factor for systemic lupus erythematosus

AbstractAutoimmune cytopenia (AIC) in children may be associated with positive antinuclear antibodies (ANA) and may progress to systemic lupus erythematosus (SLE). We evaluated the risk of progression to SLE of childhood-onset ANA-associated AIC. In the French national prospective OBS’CEREVANCE cohort, the long-term outcome of children with ANA-associated AIC (ANA titer ≥1/160) and a subgroup of children who developed SLE were described. ANA were positive in 355 of 1803 (20%) children with AIC. With a median follow-up of 5.8 (range, 0.1-29.6) years, 79 of 355 (22%) patients developed SLE at a median age of 14.5 (1.1-21.4) years; 20% of chronic immune thrombocytopenic purpura, 19% of autoimmune hemolytic anemia, and 45% of Evans syndrome. None of the patients with ANA-negative test developed SLE. Severe manifestations of SLE were observed in 21 patients, and 2 patients died. In multivariate analysis including patients with positive ANA within the first 3 months after AIC diagnosis, age >10 years at AIC diagnosis (relative risk [RR], 3.67; 95% confidence interval [CI], 1.18-11.4; P = .024) and ANA titer >1/160 (RR, 5.28; 95% CI, 1.20-23.17; P = .027) were associated with the occurrence of SLE after AIC diagnosis. ANA-associated AIC is a risk factor for progression to SLE, especially in children with an initial ANA titer >1/160 and an age >10 years at AIC diagnosis. ANA screening should be recommended in children with AIC, and patients with ANA should be monitored long-term for SLE, with special attention to the transition period. This trial was registered at www.ClinicalTrials.gov as #NCT05937828.

Thrombocytopenia in Patients with Systemic Lupus Erythematosus.

Thrombocytopenia can be one of the first manifestations of systemic lupus erythematosus and occurs in up to 40% of patients. Additionally, approximately 2% of patients with primary immune thrombocytopenia may develop systemic lupus erythematosus. Systemic lupus erythematosus is a highly heterogeneous disease, and in some patients, it may present mainly with hematological findings. Thrombocytopenia associated with systemic lupus erythematosus is also diverse, ranging from asymptomatic to severe, acute, or chronic cases. Several studies suggest that the coexistence of immune thrombocytopenia and systemic lupus erythematosus may be linked to a shared genetic background among various autoimmune diseases. Studies have reported correlations between thrombocytopenia and increased disease activity as well as kidney and central nervous system involvement in systemic lupus erythematosus. Severe thrombocytopenia is considered a poor prognostic factor in systemic lupus erythematosus. Despite this knowledge, the exact cause of reduced platelet count in systemic lupus erythematosus remains relatively unknown. Mainly, an excess of platelet destruction and/or reduced production from megakaryocytes are considered the primary factors contributing to systemic lupus erythematosus-associated thrombocytopenia. Given the prognostic significance of thrombocytopenia, there is a possibility of a pathogenic mechanistic role of thrombocytopenia and platelets in systemic lupus erythematosus. In systemic lupus erythematosus, platelets are activated and play a role in promoting autoimmune and inflammatory responses by interacting with both the innate and adaptive immunity. There is no randomized clinical trial in the treatment of systemic lupus erythematosus-related thrombocytopenia. Treatment approach of thrombocytopenia in lupus is almost similar to the treatment of immune thrombocytopenia. Considering the role of platelets in both inflammation and tissue injury, platelet activation and platelet-immune cell interaction might be important therapeutic strategies in the treatment of systemic lupus erythematosus.

FRI045 Impact Of Morbid Obesity On Lupus Hospitalizations: A Nationwide Analysis

Abstract Disclosure: F. Sami: None. S. Sami: None. K.N. Patolia: None. T. Ayub: None. Background: Obesity is a risk factor for Systemic Lupus erythematosus(SLE) and reduces quality of life in SLE patients because of disease activity and damage accrual. We aim to define the epidemiology of obese SLE patients, impact of morbid obesity on lupus hospitalizations &amp; assess healthcare economic burden from obesity. Methods: The National Inpatient Sample (NIS) was used to obtain data. Data was optimized to reflect national estimates. Patients hospitalized with a principal diagnosis of SLE with and without morbid obesity as a comorbidity were obtained from 2016-2019 NIS. Epidemiological characteristics were analyzed. Primary outcomes of mortality, length of hospital stay (LOS), &amp; total hospital charges(THC) were compared for both groups. Univariate logistic analysis was used to identify confounders and adjusted odds ratio was calculated using the multivariate logistic regression model. Results: Of 721,090 SLE hospitalizations, 7.96% had obesity as a comorbidity. For obese SLE patients, mean age was significantly lower than nonobese SLE patients(51.94 years [SD 13.86] vs 52.55 years [SD 17.30]). There were significantly more females (93.1% vs. 88%), were from age group of 40-60 years (47.5% vs 36.3%), were caucasians (50.64% vs 48.62%) and blacks (34.5% vs 30.7%)Obesity was less frequent in Hispanic and Asian lupus patients (odds ratio [OR] 0.79 and 0.33, respectively). It was significantly more in low socioeconomic SLE patients (income $1-$55,999) (38.18% vs. 33.87%) and less prevalent in high socioeconomic class with income &amp;gt; $94000 (13.3% vs 49.56%). Mortality rate was significantly higher for obese SLE patients (1.54 % vs. 1.20%, OR 1.03). Obese group had mean LOS 5.79 days vs. 5.42 days (p-value 0.009) and higher THC ($66265 vs $63742, p-value &amp;lt; 0.001). Charlson comorbidity index was higher for obese SLE (3.33 vs 2.98, p-value &amp;lt; 0.001). Obese SLE patients were significantly more common to have sepsis (10.24% vs 8.67%, OR 1.20), heart failure (6.50% vs 5.05%, OR 1.31) pulmonary embolism/deep vein thrombosis (PE/DVT) (3.86% vs. 2.69%,OR 1.45) and respiratory failure (17.91% vs 12.68%, OR 1.50), with p-value &amp;lt; 0.001 for all.It was not an independent predictor of mortality for SLE patients. Other significant predictors of mortality identified for SLE patients were age (OR 1.02), Charlson comorbidity index (OR 1.06), renal failure (OR 2.75), sepsis (OR 2.74), PE/DVT (OR 2.22), respiratory failure (OR 12.75), and stroke (OR 1.82), most of which were more common with obesity. Conclusion: Obesity with SLE is more widely seen in females, relatively younger age, low socioeconomic class, Caucasians and African-Americans. Obese SLE patients have greater mortality, THC &amp; LOS, reflecting more healthcare burden. Respiratory failure, stroke, sepsis, PE/DVT and heart failure are more common in obese patients. Therefore, weight optimization therapies for SLE may improve outcomes. Presentation: Friday, June 16, 2023

Synergistic effects of BTN3A1, SHP2, CD274, and STAT3 gene polymorphisms on the risk of systemic lupus erythematosus: a multifactorial dimensional reduction analysis.

Systemic lupus erythematosus is a complex autoimmune disorder, and evidence supports the significance of genetic polymorphisms in SLE genetic susceptibility. The aim of this study was to assess the effects of BTN3A1 (butyrophilin 3A1), SHP2 (Src homology-2 containing protein tyrosine phosphatase), CD274 (programmed cell death 1 ligand 1), and STAT3 (signal transducer-activator of transcription 3) gene interactions on SLE risk. Two hundred and ninety patients diagnosed with SLE and 370 healthy controls were recruited. A multifactor dimensionality reduction (MDR) approach was used to determine the epistasis among single nucleotide polymorphisms (SNPs) on the BTN3A1 (rs742090), SHP2 (rs58116261), CD174 (rs702275), and STAT3 (rs8078731) genes. The best risk prediction model was identified in terms of precision and cross-validation consistency. Allele A and genotype AA were negatively related to genetic susceptibility of SLE for BTN3A1 rs742090 (OR = 0.788 (0.625-0.993), P = 0.044; OR = 0.604 (0.372-0.981), P = 0.040). For STAT3 rs8078731, allele A and genotype AA were positively related to the risk of SLE (OR = 1.307 (1.032-1.654), P = 0.026; OR = 1.752 (1.020-3.010), P = 0.041). MDR analysis revealed the most significant interaction between BTN3A1 rs742090 and SHP2 rs58116261. The best risk prediction model was a combination of BTN3A1 rs742090, SHP2 rs58116261, and STAT3 rs8078731 (accuracy = 0.5866, consistency = 10/10, OR = 1.9870 (1.5964-2.4731), P = 0.001). These data indicate that risk prediction models formed by gene interactions (BTN3A1, SHP2, STAT3) can identify susceptible populations of SLE. Key Points • BTN3A1 rs742090 polymorphism was a protective factor for systemic lupus erythematosus, while STAT3 rs8078731 polymorphism was a risk factor. • There was a strong synergistic effect of BTN3A1 rs742090 and SHP2 rs58116261, and interaction among BTN3A1 rs742090, SHP2 rs58116261, and STAT3 rs8078731 constructed the best model to show association with SLE risk.

Health-related quality of life and its related factors in patients with systemic lupus erythematosus in southwest Iran: a cross-sectional study

BackgroundQuality of life (QoL) is an important measure in health assessment. It is impacted by unclear factors in Systemic Lupus Erythematosus (SLE) patients. The study aimed to investigate the factors related to QoL in SLE patients.MethodsThis cross-sectional study was performed on 140 (136 women and four men) Iranian SLE patients of Hafiz Hospital from June 2019 to August 2020. The Lupus Erythematosus Quality of Life Questionnaire (LEQoL) was used to evaluate the quality of life. The patients were evaluated with this questionnaire for four weeks in eight dimensions health, emotional health, body image, pain, planning, intimate relationships, and the burden of others. Related factors of LEQoL were evaluated using multivariable linear regression.ResultsThe mean age was 34.09(8.96) years. The total mean QoL Score was 65.5 ± 22.4. The multivariable analysis showed that duration of disease (β:-1.12, 95% CI:-1.44 to -0.79, P:0.001), physical activity(β:-12.99, 95% CI:-19.2 to -6.13, P:0.001), kidney involvement (β:-9.2, 95% CI:-16.61 to -2.79, P:0.03) and skin involvement(β:-8.7, 95% CI:-17.2 to -0.2, P:0.031) were significantly related to the total mean QOL score of SLE patients.ConclusionThe QoL of Iranian patients with SLE was low. Age and gender can be related to the decrease in the QoL of patients with SLE. Increasing the disease duration, physical activity, kidney involvement, and skin involvement can be related to the decrease in the QOL of Iranian patients with SLE.

Expression patterns of T cells-specific long noncoding RNAs in systemic lupus erythematosus patients carrying HLA risk/nonrisk alleles.

Long noncoding RNAs (LncRNAs) play key roles in the regulation of gene expression and subsequently in the pathogenesis of several autoimmune diseases. This study aimed to explore the peripheral expression levels of T-cells-specific LncRNAs and transcription factors in systemic lupus erythematosus (SLE) patients carrying either human leukocyte antigens (HLA) risk or non-risk alleles. Genotypes of HLA-DRB1 and HLA-DQB1 loci for 106 SLE patients were determined by PCR-SSP. In the next step, patients were stratified based on the presence of HLA-DRB1*03 and/or DRB1*16 allele groups (HLA risk alleles positive or HLA-RPos) or carrying other DRB1 allele groups (HLA-RNeg). Then, transcript levels of LncRNAs (IFNG-AS1, RMRP, Th2LCR, and DQ786243) and mRNAs for transcription factors (Foxp3, Gata3, and Tbx21) were measured using qRT-PCR and compared between two subgroups of patients. Totally, 47 cases were classified as HLA-RPos and 59 cases as HLA-RNeg patients. The HLA-RPos patients showed decreased transcript levels of DQ786243 (p = .001) and elevated expression of IFNG-AS1 (p = .06) and T-bet mRNA (p = .03) compared to the HLA-RNeg group. We observed significantly lower expression of Th2LCR (p < .0001) and DQ786243 (p = .001) and higher expression of Tbx21 (p = .009) and Foxp3 (p = .02) in DR3-positive versus DR3-negative patients. Likewise, decreased transcript levels of DQ786243 (p = .02) and RMRP (p = .003) were observed in DR16-positive versus DR16-negative patients. ROC curve analysis revealed the potential of DQ786243 and RMRP as biomarkers in SLE disease based on the carriage of HLA risk alleles. Our results indicate that the contribution of multiple T cell subsets in SLE disease progression as judged by expression analysis of LncRNAs and transcription factors can be inspired by the inheritance of HLA risk/nonrisk alleles is SLE patients.

Telomere length and its association with systemic lupus erythematosus in an Asian population: A Mendelian randomization study.

To investigate whether shorter telomere length is a causal risk factor for systemic lupus erythematosus (SLE) in the Asian population. We applied the two-sample Mendelian randomization (MR) method to the pooled statistics from a genome-wide association study (GWAS) of 6,707 SLE cases and 16,047 controls. We selected nine single-nucleotide polymorphisms (SNPs) with genome-wide significance as instrumental variables for telomere length. The main analysis was carried out by the random-effects inverse-variance weighted (IVW) method. Horizontal pleiotropy was evaluated by the intercept of MR-Egger regression. A potentially causal relationship between longer genetically predicted telomere length and increased risk of systemic lupus erythematosus (OR = 1.72, 95%CI: 1.21, 2.46, p = 0.01) was observed. The MR-Egger regression demonstrated an intercept proximal to zero (intercept = 0.017, p = 0.69), which does not provide evidence of the presence of horizontal pleiotropy. Our findings provided evidence supporting a potential causal relationship between longer telomere length and increased risk of systemic lupus erythematosus.

Gut microbiota: a newly identified environmental factor in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that predominantly affects women of childbearing age and is characterized by the damage to multiple target organs. The pathogenesis of SLE is complex, and its etiology mainly involves genetic and environmental factors. At present, there is still a lack of effective means to cure SLE. In recent years, growing evidence has shown that gut microbiota, as an environmental factor, triggers autoimmunity through potential mechanisms including translocation and molecular mimicry, leads to immune dysregulation, and contributes to the development of SLE. Dietary intervention, drug therapy, probiotics supplement, fecal microbiome transplantation and other ways to modulate gut microbiota appear to be a potential treatment for SLE. In this review, the dysbiosis of gut microbiota in SLE, potential mechanisms linking gut microbiota and SLE, and immune dysregulation associated with gut microbiota in SLE are summarized.

Environmental risk factors of systemic lupus erythematosus: a case–control study

Systemic lupus erythematosus (SLE) is a complicated chronic autoimmune disorder. Several genetic and environmental factors were suggested to be implicated in its pathogenesis. The main objective of this study was to examine how exposure to selected environmental factors was associated with SLE risk to support the development of disease preventive strategies. A case–control study was conducted at the Rheumatology outpatient clinic of Alexandria Main University Hospital, in Alexandria, Egypt. The study sample consisted of 29 female SLE patients, and 27 healthy female controls, who matched the cases on age and parity. Data were collected by a structured interviewing questionnaire. Blood levels of lead, cadmium, and zinc of all participants were assessed by flame atomic absorption spectrometry. The multivariate stepwise logistic regression model revealed that five factors showed significant association with SLE, namely living near agricultural areas, passive smoking, blood lead levels ≥ 0.075 mg/L, and exposure to sunlight (odds ratio (OR) 58.556, 95% confidence interval (CI) 1.897–1807.759, OR 24.116, 95% CI 1.763–329.799, OR 18.981, 95% CI 1.228–293.364, OR 9.549, 95% CI 1.299–70.224, respectively). Whereas walking or doing exercise were significantly protective factors (P = 0.006). The findings of this study add to the evidence that SLE can be environmentally induced. Preventive measures should be taken to address the environmental risk factors of SLE.

Infection in systemic lupus erythematosus-associated diffuse alveolar hemorrhage: a potential key to improve outcomes.

This study aimed to investigate the clinical characteristics, outcomes, and associated factors of patients with systemic lupus erythematosus-associated diffusive alveolar hemorrhage (SLE-DAH) stratified by infection status in a national representative cohort. This single-center retrospective study included 124 consecutive patients with SLE-DAH in a tertiary care center between 2006 and 2021. The diagnosis of DAH was made based on a comprehensive evaluation of clinical manifestations, laboratory and radiologic findings, and bronchoalveolar lavage. Demographics, clinical features, and survival curves were compared between patients with bacterial, non-bacterial, and non-infection groups. Univariate and multivariate logistic regression analyses were performed to determine the factors independently associated with bacterial infection in SLE-DAH. Fifty-eight patients with SLE-DAH developed bacterial infection after DAH occurrence, thirty-two patients developed fungal and/or viral infection, and thirty-four patients were categorized as non-infection. The bacterial infection group have a worse prognosis (OR 3.059, 95%CI 1.469-6.369, p = 0.002) compared with the other two groups, with a mortality rate of 60.3% within 180days after DAH occurrence. Factors independently associated with bacterial infections in SLE-DAH included hematuria (OR 4.523, 95%CI 1.068-19.155, p = 0.040), hemoglobin drop in the first 24h after DAH occurred (OR 1.056, 95%CI 1.001-1.115, p = 0.049), and anti-Smith antibody (OR 0.167, 95%CI 0.052-0.535, p = 0.003). Glucocorticoid pulse therapy and cyclophosphamide were administered in more than 50% of patients regardless of their infectious status. According to clinical experience at our hospital and in previous studies, we recommended a comprehensive management algorithm for SLE-DAH based on infection stratification. Infection, especially bacterial infection, is a severe complication and prognostic factor of SLE-DAH. Comprehensive management strategies, including diagnosis, evaluation, treatment, and monitoring, based on infection stratification may fundamentally improve outcomes of patients with SLE-DAH. Key Points • Bacterial infection is an important, but neglected, prognosis factor of systemic lupus erythematosus (SLE)-associated diffusive alveolar hemorrhage (DAH). • Hematuria, hemoglobin drop, and anti-Smith antibody can independently predict bacterial infections in SLE-DAH. • We put forward a comprehensive management algorithm based on infection stratification for SLE-DAH.

A cross-sectional study of systemic lupus erythematosus patients complicated with infection

Objectives and Introduction The purpose of this study was to determine the prevalence and influencing factors of systemic lupus erythematosus (SLE) patients complicated with infection having multi-system involvement and to analyze the influencing factors of early CMV and fungal infection. Methods We conducted a cross-sectional study of hospitalized SLE patients complicated with infection. Participants had an average age of 44.80 ± 17.30, with 152 being female (89.94%). Clinical data and laboratory results were collected from medical records. Receiver operating characteristic (ROC) curves were plotted, and sensitivity and specificity were calculated. Results Univariate analysis showed that systemic lupus erythematosus disease activity index-2000 (SLEDAI-2k), red blood cell, platelets, hemoglobin, lymphocytes, IgG, IgM, C3, C4, albumin and globulin were significantly associated with SLE patients with infection complicated with multi-system involvement. After multivariable analysis, the following variables remained significant: Hemoglobin, CD4 lymphocyte, IgM and SM ( p &lt; 0.05). ROC curve analysis showed the areas under the curve of Hb, CD4 count, and IgM for the differential diagnosis of SLE with infection complicated with multisystem involvement being 0.646, 0.627, and 0.610. Then, the sensitivities of 73.3%, 53.3%, and 73.3% were observed with the specificities of 54.1%, 69.7%, and 48.6%, respectively. Conclusions Our results demonstrated that hemoglobin, CD4 lymphocyte value, IgM and anti SM antibody had significant value in monitoring multi-system involvement in SLE patients complicated with infection. Besides, intrinsic lymphatic count disturbances associated with SLE disease can cause infections by opportunistic pathogens such as fungi.

Interferon-gamma (IFN-γ) intronic variant (rs2430561) is a risk factor for systemic lupus erythematosus: Observation from a meta-analysis.

The role of interferon-gamma (IFN-γ) in autoimmune disorders has been well documented. Elevated levels of IFN-γ are observed in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and are linked with disease severity. Single nucleotide polymorphism in the intronic region of the IFN-γ gene (+874 T>A rs2430561) has been associated with susceptibility to the development of RA and SLE; however, the reports remained contradictories. We conducted a meta-analysis using earlier published articles to reach a valid conclusion on the role of IFN-γ polymorphism (+874 T>A) in autoimmune diseases. Various online databases such as PubMed, Google Scholar, Science Direct, and Scopus were searched to find eligible reports for inclusion in the present analysis. Two independent authors extracted eligible studies and data. The meta-analysis was performed by comprehensive meta-analysis software (CMA) v.3.1. Trial sequential analysis was performed to test whether enough case-control studies have already been conducted worldwide to reach a valid observation. Six published reports on the role of IFN-γ +874 T>A in SLE and four in RA were found after searching various databases. However, out of those six studies in SLE, in one study, the distribution of genotypes was not following the hardy-Weinberg equilibrium. In RA, three studies were deviated out of four reports. Thus, a total of five studies comprising 1440 SLE patients and 1748 controls were considered for the present meta-analysis. Meta-analysis showed a significant association between IFN-γ +874 T>A variants with susceptibility to SLE (homozygous comparison: p = 0.036, OR = 1.592, heterozygous model: p = 0.042, OR = 1.507, dominant model: p = 0.002, OR = 1.309). IFN-γ +874 T>A variant is associated with predisposition to SLE development.

Diagnosis of tuberculosis with autoimmune hepatitis–systemic lupus erythematosus overlap syndrome: a case report

BackgroundThere is ample evidence indicating that immunosuppressive therapy or immune dysregulation in systemic lupus erythematosus increases the risk for tuberculosis. Interestingly, a few case reports suggest that tuberculosis could also be a risk factor for systemic lupus erythematosus and other autoimmune diseases.Case presentationWe report the case of a 32-year-old Indian patient who was co-diagnosed with tuberculosis, systemic lupus erythematosus, and autoimmune hepatitis without any history of prior immunosuppression. This stresses the complex relationship between tuberculosis and autoimmune diseases.ConclusionFurther research is warranted in this field to unfold the complex relationship between tuberculosis and systemic lupus erythematosus. It is essential to establish clear guidelines for the management of coexisting tuberculosis and systemic lupus erythematosus to promote individualized treatment.