Risk Of Systemic Lupus Erythematosus Research Articles

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

Immunogenetic Relationship of HLA-G 14 bp Insertion/Deletion Polymorphism and Toll-Like Receptor 9 with Systemic Lupus Erythematosus in Egyptian Patients: A Case-Control Study.

IntroductionThe level of expression of the immunoregulatory human leukocyte antigen-G (HLA-G) has been suggested to play a role in the immunopathogenesis of systemic lupus erythematosus (SLE). A 14 bp insertion/deletion (ins/del) polymorphism in the 3ˊuntranslated region of HLA-G gene may influence the level of expression. The role of Toll-like receptor 9 (TLR9) in the pathogenesis of SLE has been highlighted. Data among Egyptian patients are quite limited.PurposeTo detect the association of HLA-G 14 bp ins/del gene polymorphism with the susceptibility to SLE and to correlate TLR9 serum level with disease activity among Egyptian patients.Patients and MethodsA case-control study that included 102 SLE female patients and 102 healthy matched volunteers as controls was carried out. Disease activity in patients was determined using the modified Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). HLA-G 14 bp ins/del genotype was detected by polymerase chain reaction (PCR). TLR9 serum level was estimated using enzyme-linked immunosorbent assay (ELISA) technique.ResultsThe ins/ins genotype was significantly increased among SLE patients compared to healthy subjects (58.8% vs 9.8%; odds ratio [OR] = 11.79, P < 0.001). The 14 bp ins allele was significantly more frequent in SLE patients than in healthy subjects (65.7% vs 27.9%, respectively) and significantly associated with an increased risk of SLE (OR 4.94, P < 0.001). The mean TLR9 serum level showed a significant increase in SLE patients compared to healthy subjects (397.04±137.86 vs 195.22±45.14 ng/L, p < 0.001) and was significantly associated with disease activity as well as to patients’ HLA-G genotypes (p < 0.001).ConclusionAmong Egyptian population, HLA-G 14 bp ins/ins homozygous genotype and ins allele may constitute a potential risk for SLE susceptibility, while TLR9 serum level is significantly associated with disease activity.

Association of High Calcitriol Serum Levels and Its Hydroxylation Efficiency Ratio with Disease Risk in SLE Patients with Vitamin D Deficiency.

Vitamin D (calcidiol) deficiency in systemic lupus erythematosus (SLE) is more frequent than in healthy subjects (HS); it is associated with clinical activity and damage in SLE. Although calcidiol is considered the best indicator of the vitamin D serum status, its deficiency could not reflect its hydroxylation efficiency ratio and calcitriol serum status. This study was aimed at assessing the association of calcidiol and calcitriol serum levels and its hydroxylation efficiency ratio with the risk to clinical and renal disease activities in SLE patients. A cross-sectional study was conducted in 308 SLE and HS women; calcidiol and calcitriol serum levels were evaluated by immunoassays. SLE patients showed lower calcidiol serum levels vs. HS (21.2 vs. 24.2 ng/mL; p < 0.001). Active SLE patients presented higher calcidiol/calcitriol ratio scores vs. inactive SLE patients (2.78 vs. 1.92 pg/ng; p = 0.02), and SLE patients with renal disease activity showed a pattern of calcidiol-deficient levels (19.5 vs. 25.3 ng/mL; p < 0.04) with higher calcitriol levels (47 pg/mL vs. 41.5 pg/mL; p = 0.02) and calcidiol/calcitriol ratio scores (2.13 vs. 1.54 pg/ng; p < 0.02) compared to SLE patients without renal disease activity. Calcidiol levels were negatively correlated with calcitriol levels (r = −0.26; p = 0.001) and urine proteins (mg/dL) (r = −0.39; p < 0.01). Regarding calcitriol levels, it was positively correlated with the blood lymphocyte count (r = 0.30; p < 0.001) and negatively correlated with the glomerular filtration rate (r = −0.28; p = 0.001). Moreover, the calcitriol/calcidiol ratio was positively correlated with urine proteins (r = 0.38; p < 0.01). The calcidiol deficiency (OR = 2.27; 95% CI = 1.15-4.49; p < 0.01), high calcitriol levels (T3rd, OR = 4.19, 95% CI = 2.23-7.90; p < 0.001), and a high calcitriol/calcidiol ratio score (T3rd, OR = 5.93, 95% CI: 3.08-11.5; p < 0.001) were associated with the risk for SLE. In conclusion, a pattern of calcidiol deficiency with high calcitriol serum levels and a high vitamin D hydroxylation efficiency ratio was associated with disease risk in SLE patients.

Genetic and transcriptomic analyses support a switch to lytic phase in Epstein Barr virus infection as an important driver in developing Systemic Lupus Erythematosus

To investigate the molecular mechanisms through which Epstein-Barr virus (EBV) may contribute to Systemic Lupus Erythematosus (SLE) pathogenesis, we interrogated SLE genetic risk loci for signatures of EBV infection. We first compared the gene expression profile of SLE risk genes across 459 different cell/tissue types. EBV-infected B cells (LCLs) had the strongest representation of highly expressed SLE risk genes. By determining an SLE risk allele effect on gene expression (expression quantitative trait loci, eQTL) in LCLs and 16 other immune cell types, we identified 79 SLE risk locus:gene pairs putatively interacting with EBV infection. A total of 10 SLE risk genes from this list (CD40, LYST, JAZF1, IRF5, BLK, IKZF2, IL12RB2, FAM167A, PTPRC and SLC15A) were targeted by the EBV transcription factor, EBNA2, differentially expressed between LCLs and B cells, and the majority were also associated with EBV DNA copy number, and expression level of EBV encoded genes. Our final gene network model based on these genes is suggestive of a nexus involving SLE risk loci and EBV latency III and B cell proliferation signalling pathways. Collectively, our findings provide further evidence to support the interaction between SLE risk loci and EBV infection that is in part mediated by EBNA2. This interplay may increase the tendency towards EBV lytic switching dependent on the presence of SLE risk alleles. These results support further investigation into targeting EBV as a therapeutic strategy for SLE.

Toll-like receptor 5 and Toll-like receptor 9 single nucleotide polymorphisms and risk of systemic lupus erythematosus and nephritis in Egyptian patients

BackgroundToll-like (TLRs) play a crucial role in both adaptive and innate immunity. The aim of the present study was to assess the association of TLR5-rs5744168, TLR9-rs187084, and TLR9-rs352140 single nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN) in Egyptian patients.ResultsThe C allele and homozygous CC genotype of the TLR9-rs352140 in co-dominant and recessive models were more prevalent in SLE patients than controls (P = 0.047, P = 0.017, and P = 0.005 respectively). In contrast, allelic and genotyping distribution of TLR5-rs5744168 and TLR9-rs187084 SNPs showed no association with the risk of SLE. The T allele of the TLR5-rs5744168 was more prevalent in LN patients than controls (P = 0.021). The homozygous TT genotype of TLR5-rs5744168 SNP was more prevalent in LN patients in the co-dominant and the recessive models than controls (P = 0.036 and P = 0.011 respectively). The C allele of the TLR9-rs352140 was more prevalent in LN patients than controls (P = 0.015). The homozygous CC genotype of the TLR9-rs352140 SNP was more prevalent in LN than controls in co-dominant and recessive models (P = 0.002 and P < 0.001). In the recessive model of the TLR5-rs5744168 SNP, the TT genotype was found in 3.2% of the SLE patients while none of the SLE patients without LN or controls had TT genotype (P = 0.036). Also, in the recessive model of the TLR9-rs352140 SNP, the CC genotype was significantly more frequent in SLE patients with LN than without LN (44.4% vs 29.9%, P = 0.045).ConclusionOur results support the potential role of TLR5-rs5744168 SNP and TLR9-rs3532140 SNP not only in increasing the risk for development of SLE, but also in increasing the risk of LN in SLE patients among the Egyptian population.

Single-cell expression quantitative trait loci (eQTL) analysis of SLE-risk loci in lupus patient monocytes

BackgroundWe performed expression quantitative trait locus (eQTL) analysis in single classical (CL) and non-classical (NCL) monocytes from patients with systemic lupus erythematosus (SLE) to quantify the impact of well-established genetic risk alleles on transcription at single-cell resolution.MethodsSingle-cell gene expression was quantified using qPCR in purified monocyte subpopulations (CD14++CD16− CL and CD14dimCD16+ NCL) from SLE patients. Novel analysis methods were used to control for the within-person correlations observed, and eQTLs were compared between cell types and risk alleles.ResultsThe SLE-risk alleles demonstrated significantly more eQTLs in NCLs as compared to CLs (p = 0.0004). There were 18 eQTLs exclusive to NCL cells, 5 eQTLs exclusive to CL cells, and only one shared eQTL, supporting large differences in the impact of the risk alleles between these monocyte subsets. The SPP1 and TNFAIP3 loci were associated with the greatest number of transcripts. Patterns of shared influence in which different SNPs impacted the same transcript also differed between monocyte subsets, with greater evidence for synergy in NCL cells. IRF1 expression demonstrated an on/off pattern, in which expression was zero in all of the monocytes studied from some individuals, and this pattern was associated with a number of SLE risk alleles. We observed corroborating evidence of this IRF1 expression pattern in public data sets.ConclusionsWe document multiple SLE-risk allele eQTLs in single monocytes which differ greatly between CL and NCL subsets. These data support the importance of the SPP1 and TNFAIP3 risk variants and the IRF1 transcript in SLE patient monocyte function.

Nucleic Acid-Sensing and Interferon-Inducible Pathways Show Differential Methylation in MZ Twins Discordant for Lupus and Overexpression in Independent Lupus Samples: Implications for Pathogenic Mechanism and Drug Targeting.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune inflammatory disease with genomic and non-genomic contributions to risk. We hypothesize that epigenetic factors are a significant contributor to SLE risk and may be informative for identifying pathogenic mechanisms and therapeutic targets. To test this hypothesis while controlling for genetic background, we performed an epigenome-wide analysis of DNA methylation in genomic DNA from whole blood in three pairs of female monozygotic (MZ) twins of European ancestry, discordant for SLE. Results were replicated on the same array in four cell types from a set of four Danish female MZ twin pairs discordant for SLE. Genes implicated by the epigenetic analyses were then evaluated in 10 independent SLE gene expression datasets from the Gene Expression Omnibus (GEO). There were 59 differentially methylated loci between unaffected and affected MZ twins in whole blood, including 11 novel loci. All but two of these loci were hypomethylated in the SLE twins relative to the unaffected twins. The genes harboring these hypomethylated loci exhibited increased expression in multiple independent datasets of SLE patients. This pattern was largely consistent regardless of disease activity, cell type, or renal tissue type. The genes proximal to CpGs exhibiting differential methylation (DM) in the SLE-discordant MZ twins and exhibiting differential expression (DE) in independent SLE GEO cohorts (DM-DE genes) clustered into two pathways: the nucleic acid-sensing pathway and the type I interferon pathway. The DM-DE genes were also informatically queried for potential gene–drug interactions, yielding a list of 41 drugs including a known SLE therapy. The DM-DE genes delineate two important biologic pathways that are not only reflective of the heterogeneity of SLE but may also correlate with distinct IFN responses that depend on the source, type, and location of nucleic acid molecules and the activated receptors in individual patients. Cell- and tissue-specific analyses will be critical to the understanding of genetic factors dysregulating the nucleic acid-sensing and IFN pathways and whether these factors could be appropriate targets for therapeutic intervention.

Anti-Double-Stranded DNA Antibodies Recognize DNA Presented on HLA Class II Molecules of Systemic Lupus Erythematosus Risk Alleles.

Specific HLA class II alleles are associated with susceptibility to systemic lupus erythematosus (SLE). The role of HLA class II molecules in SLE pathogenesis remains unclear, although anti-DNA antibodies are specific to SLE and correlate with disease activity. We previously demonstrated that misfolded proteins bound to HLA class II molecules are specific targets for the autoantibodies produced in autoimmune diseases. This study was undertaken to validate our hypothesis that DNA binds to HLA class II molecules in a manner similar to that of misfolded proteins and that DNA bound to HLA class II molecules is involved in SLE pathogenesis. We analyzed the binding of DNA to HLA class II molecules, as well as the response of cells expressing anti-DNA B cell receptors (BCRs) to cells expressing the DNA/HLA class II complex. Efficient binding of DNA to HLA class II molecules was observed in risk alleles of SLE, such as HLA-DRB1*15:01. The efficiency of DNA binding to each HLA-DR allele was positively associated with the risk of SLE conferred by the HLA-DR allele. In addition, reporter cells carrying anti-DNA BCRs were activated by cells expressing DNA/HLA class II complexes. These results provide evidence that DNA bound to HLA class II molecules is involved in SLE pathogenesis.

Association Between a History of Nontyphoidal Salmonella and the Risk of Systemic Lupus Erythematosus: A Population-Based, Case-Control Study.

ObjectiveWe investigated the correlation between nontyphoidal Salmonella (NTS) infection and systemic lupus erythematosus (SLE) risk.MethodsThis case-control study comprised 6,517 patients with newly diagnosed SLE between 2006 and 2013. Patients without SLE were randomly selected as the control group and were matched at a case-control ratio of 1:20 by age, sex, and index year. All study individuals were traced from the index date back to their NTS exposure, other relevant covariates, or to the beginning of year 2000. Conditional logistic regression analysis was used to analyze the risk of SLE with adjusted odds ratios (aORs) and 95% confidence intervals (CIs) between the NTS and control groups.ResultsThe mean age was 37.8 years in the case and control groups. Females accounted for 85.5%. The aOR of having NTS infection were significantly increased in SLE relative to controls (aOR, 9.20; 95% CI, 4.51-18.78) in 1:20 sex-age matching analysis and (aOR, 7.47; 95% CI=2.08-26.82) in propensity score matching analysis. Subgroup analysis indicated that the SLE risk was high among those who dwelled in rural areas; had rheumatoid arthritis, multiple sclerosis, or Sjogren’s syndrome; and developed intensive and severe NTS infection during admission.ConclusionsExposure to NTS infection is associated with the development of subsequent SLE in Taiwanese individuals. Severe NTS infection and other autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, or Sjogren’s syndrome also contributed to the risk of developing SLE.

Association of CD14 genetic variants and circulating level with systemic lupus erythematosus risk in Egyptian children and adolescents.

Aim: To demonstrate whether sCD14 and CD14 (rs2569190 A/G and rs2569191 C/T) genetic variants are associated with systemic lupus erythematosus (SLE) risk, for the first time, in Egyptian pediatrics and adolescents. Materials & methods: sCD14 concentrations were determined in plasma of 95 SLE cases and 98 healthy controls using ELISA assay. Genotyping was performed using TaqMan technology. Results: sCD14 levels were elevated in SLE. Individuals with T, CTand TTgenotypes in rs2569191 were of significant risk (odds ratio =1.471-2.035, 95% CI=1.138-3.471) and those with combined CT+TTand haplotype GTwere of higher risk of SLE (odds ratio =1.660-1.758, 95% CI=1.003-3.106, p<0.05). sCD14 levels and CD14 polymorphism were not correlated with SLE clinical and laboratory features. Conclusion: In SLE, sCD14 levels are associated with rs2569190 A/G. Genotype CT+TTin rs2569191 C/T and haplotype GTare associated with SLE risk in Egyptian pediatric and adolescents.

Association Between a History of Dengue Fever and the Risk of Systemic Autoimmune Rheumatic Diseases: A Nationwide, Population-Based Case-Control Study

Purpose: To determine the association between a history of clinically diagnosed dengue infection and the risk of systemic autoimmune rheumatic diseases (SARDs).Methods: Using claims data from the 1997–2013 Taiwanese National Health Insurance Research Database, we included 74,422 patients who were diagnosed with SARDs and 297,688 patients without SARDs who were matched (in a 1:4 ratio) for age, sex, year of SARDs index date, and city of residence. The associations between the development of SARDs and a history of dengue infection (International Classification of Diseases, Ninth Revision, Clinical Modification code 061) were investigated using conditional logistic regression analysis shown as odds ratios (ORs) with 95% confidence intervals (CIs) after adjusting for potential confounders.Results: We included 17,126 patients with systemic lupus erythematosus (SLE), 15,531 patients with Sjogren's syndrome (SS), 37,685 patients with rheumatoid arthritis (RA), 1,911 patients with systemic sclerosis (SSc), 1,277 patients with dermatomyositis (DM), and 892 patients with polymyositis (PM). SLE (OR, 4.55; 95% CI, 2.77–7.46; p <0.001) risk was significantly associated with a history of dengue infection. However, no statistically significant association was found between dengue infection and SS (OR, 1.41; 95% CI, 0.88–2.26; p = 0.155), RA (OR, 1.03; 95% CI, 0.70–1.50; p = 0.888), SSc (OR, 1.97; 95% CI, 0.38–10.29; p = 0.420), DM (OR, 0.54; 95% CI, 0.04–7.27; p = 0.641), or PM (OR, 2.08; 95% CI, 0.23–18.79; p = 0.513).Conclusion: This study revealed that a history of dengue infection was significantly associated with the risk of SLE, but not SS, RA, SSc, DM, or PM.

Association Between the Interferon-γ +874 T/A Polymorphism and the Risk and Clinical Manifestations of Systemic Lupus Erythematosus: A Preliminary Study.

BackgroundInterferon-gamma (IFN-γ) is a pivotal cytokine involved in the development of systemic lupus erythematosus (SLE). The IFN-γ +874 T/A polymorphism has been shown to be related to the susceptibility to SLE in other races, but this has not been investigated in the Chinese Han population.MethodsWe designed this study to interpret the potential correlation between this polymorphism and SLE risk in a Chinese Han population. We included 374 SLE patients and 405 controls in this study. Odds ratios and relevant 95% confidence intervals were figured out to evaluate the potential strength of the association.ResultsData revealed that the IFN-γ +874 T/A polymorphism showed an association with an enhanced risk of SLE in this Chinese Han population. TA or TA +AA genotype carriers showed an increased risk of developing SLE. Subgroup analyses found that this polymorphism elevated the risk of SLE among females. Additionally, this polymorphism was associated with clinical manifestations of SLE including lupus nephritis, proteinuria, anti-dsDNA antibodies, anti-Sm antibodies, and SLICC/ACR damage index. Furthermore, we conducted a meta-analysis and found that this polymorphism was associated with the risk of SLE, especially among Asians.ConclusionTotally, this study detects that the IFN-γ +874 T/A polymorphism is related to the risk and clinical manifestations of SLE in a Chinese Han population.

Association of microRNA-34a rs2666433 (A/G) Variant with Systemic Lupus Erythematosus in Female Patients: A Case-Control Study.

Several microRNAs (miRNAs) are associated with autoimmune disease susceptibility and phenotype, including systemic lupus erythematosus (SLE). We aimed to explore for the first time the role of the miRNA-34a gene (MIR34A) rs2666433A > G variant in SLE risk and severity. A total of 163 adult patients with SLE and matched controls were recruited. Real-Time allelic discrimination PCR was applied for genotyping. Correlation with disease activity and clinic-laboratory data was done. The rs2666433 variant conferred protection against SLE development under heterozygous [A/G vs. G/G; OR = 0.57, 95%CI = 0.34–0.95], homozygous [A/A vs. G/G; OR = 0.52, 95%CI = 0.29–0.94], dominant [A/G + A/A vs. GG; OR = 0.55, 95%CI = 0.35–0.88], and log-additive [OR = 0.71, 95%CI = 0.53–0.95] models. Data stratification by sex revealed a significant association with SLE development in female participants under heterozygous/homozygous models (p-interaction = 0.004). There was no clear demarcation between SLE patients carrying different genotypes regarding the disease activity index or patients stratified according to lupus nephritis. Enrichment analysis confirmed the implication of MIR34A in the SLE pathway by targeting several genes related to SLE etiopathology. In conclusion, although the MIR34A rs2666433 variant conferred protection against developing SLE disease in the study population, it showed no association with disease activity. Replication studies in other populations are warranted.

Lupus Susceptibility Region Containing CDKN1B rs34330 Mechanistically Influences Expression and Function of Multiple Target Genes, Also Linked to Proliferation and Apoptosis.

In a recent genome-wide association study, a significant genetic association between rs34330 of CDKN1B and risk of systemic lupus erythematosus (SLE) in Han Chinese was identified. This study was undertaken to validate the reported association and elucidate the biochemical mechanisms underlying the effect of the variant. We performed an allelic association analysis in patients with SLE, followed by a meta-analysis assessing genome-wide association data across 11 independent cohorts (n = 28,872). In silico bioinformatics analysis and experimental validation in SLE-relevant cell lines were applied to determine the functional consequences of rs34330. We replicated a genetic association between SLE and rs34330 (meta-analysis P = 5.29 × 10-22 , odds ratio 0.84 [95% confidence interval 0.81-0.87]). Follow-up bioinformatics and expression quantitative trait locus analysis suggested that rs34330 is located in active chromatin and potentially regulates several target genes. Using luciferase and chromatin immunoprecipitation-real-time quantitative polymerase chain reaction, we demonstrated substantial allele-specific promoter and enhancer activity, and allele-specific binding of 3 histone marks (H3K27ac, H3K4me3, and H3K4me1), RNA polymerase II (Pol II), CCCTC-binding factor, and a critical immune transcription factor (interferon regulatory factor 1 [IRF-1]). Chromosome conformation capture revealed long-range chromatin interactions between rs34330 and the promoters of neighboring genes APOLD1 and DDX47, and effects on CDKN1B and the other target genes were directly validated by clustered regularly interspaced short palindromic repeat (CRISPR)-based genome editing. Finally, CRISPR/dead CRISPR-associated protein 9-based epigenetic activation/silencing confirmed these results. Gene-edited cell lines also showed higher levels of proliferation and apoptosis. Collectively, these findings suggest a mechanism whereby the rs34330 risk allele (C) influences the presence of histone marks, RNA Pol II, and IRF-1 transcription factor to regulate expression of several target genes linked to proliferation and apoptosis. This process could potentially underlie the association of rs34330 with SLE.

Association between toxic organochlorine levels in human serum and systemic lupus erythematosus.

Organochlorines (OCs) are groups of highly toxic pesticides with known immunotoxicity. The present work aimed to study the potential association between serum residues of OCs and the risk of developing systemic lupus erythematosus (SLE) as well as correlating to the clinical-laboratory manifestations in a sample of Egyptian SLE patients. A cross-sectional study was conducted on 132 patients environmentally exposed to OCs. Patients were diagnosed as SLE based on the American College of Rheumatology (ACR) revised criteria. Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score was calculated to stratify the disease severity. Blood and urine samples were collected to measure the levels of OCs, serological markers, and urinary protein. The most frequently detected OCs were p,p'-DDE; lindane; and hexachlorobenzene (HCB). The risk of developing SLE was significantly associated with detected p,p'-DDE and HCB (B value 7.704 and 14.33, respectively). Hexachlorobenzene, in addition, was significantly associated with increased SLEDAI-2K score and polycythemia. Lindane was significantly associated with hypocomplementemia, cardiac manifestations of SLE, anemia, and leucopenia. In conclusion, the detected OCs p,p'-DDE and HCB are associated with increased risk of SLE in Egyptian patients and correlates to the manifestations of disease severity.

Association of TNFAIP3 gene polymorphism (rs5029939) with susceptibility and clinical phenotype of systemic lupus erythematosus.

Objectives This study aims to investigate the association of the tumor necrosis factor-alpha inducible protein 3 (TNFAIP3) (rs5029939) gene single nucleotide polymorphism (SNP) with the risk of systemic lupus erythematosus (SLE) and its clinical manifestations in a cohort of SLE patients.Patients and methods This study included a total of 180 participants (18 males, 72 females; mean age: 30.9±10.1 years; range 17 to 59 years) including 90 SLE patients and 90 healthy controls between March 2017 and February 2020. The TNFAIP3 rs5029939 gene polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in all participants.Results There was a significant difference in genotype distribution of the TNFAIP3 rs5029939 SNP between SLE patients and healthy controls, where CG genotype was more common in SLE patients (53.3%) than controls (11.1%) (p=0.001). We found a significant difference in G allele frequency of TNFAIP3 (rs5029939) (37.8% with SLE vs. 5.6% with controls, p=0.001). Genotype CG was significantly associated with lupus nephritis and neuropsychiatric manifestations (p<0.05). Although the response to treatment was numerically higher with the genotype CC, it did not reach statistical significance (p=0.4).Conclusion Our study suggests that TNFAIP3 rs5029939 gene polymorphism is associated with SLE susceptibility and may have an impact on its clinical phenotype. As such association differs among populations of diverse ethnic backgrounds, larger genome-wide association studies are warranted to further elucidate genetic associations.

Association of macronutrients and dietary patterns with risk of systemic lupus erythematosus in the Black Women’s Health Study

Systemic lupus erythematosus (SLE) affects African-American (AA) women disproportionately. The few prospective studies assessing dietary intake in relation to risk of SLE have been conducted in predominantly white populations and have been null. The present study assessed associations of macronutrients and dietary patterns with risk of SLE in AA women. Data from the Black Women's Health Study was collected prospectively via biennial questionnaires starting in 1995. Participants completed a self-administered 68-item FFQ in 1995. Self-reported SLE was verified through medical record review. We used multivariable (MV) Cox regression models to estimate HRs and 95% CIs for macronutrients, carbohydrates, proteins, total fats, PUFAs, ω-3 fatty acids, ω-6 fatty acids, MUFAs, saturated fats, trans fatty acids, Alternative Healthy Eating Index score, vegetable/fruit and meat/fried food dietary patterns, and a reduced rank regression (RRR)-derived dietary pattern in relation to SLE risk. We confirmed a total of 114 incident cases of SLE among 51,934 women during 1995-2015. MVHRs and 95% CIs for the highest quintile of intake versus the lowest were HR: 1.96, 95% CI: 1.02, 3.67 for carbohydrates; HR: 0.66, 95% CI: 0.37, 1.18 for protein; and HR: 0.54, 95% CI: 0.28, 1.01 for total fats. MUFAs, saturated fatty acids, and trans fatty acids were significantly associated with a lower risk of SLE. An RRR-derived factor, rich in fruits and sugar-sweetened drinks and low in margarines and butter, red and processed meats, fried chicken, poultry, and eggs, which explained 53.4% of the total variation of macronutrients, was the only food pattern associated with increased SLE risk (HR: 1.88, 95% CI: 1.06, 3.35). These analyses suggest that a diet high in carbohydrates and low in fats is associated with increased SLE risk in AA women.

The relation between clinical and objective gait scores in clubfoot patients with and without a relapse

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with complex genetic inheritance. Many reports have provided evidence that signal transducer and activator of transcription-4 (STAT4) may participate in the pathogenesis of SLE.The aim was to investigate the clinical significance and possible association of STAT4 (G/T) genetic polymorphism and the susceptibility to SLE in a cohort of Egyptian female patients.Sixty-five Egyptian SLE female patients and 100 age and sex-matched unrelated female healthy blood donors who served as controls, were included in the study. STAT4 genotyping was performed by real time PCR-allelic discrimination technique.STAT4 genotyping in patients revealed that 63.1% had GG, 32.3% GT and 6.15% wild (TT) genotype. There was a non-significant difference in the distribution of STAT4 genotypes between patients and controls. Vasculitis, photosensitivity and lupus nephritis were significantly increased in patients with the homomutant (GG and TT) compared to heteromutant (GT) genotype (p = 0.01, p = 0.04 and p < 0.01 respectively). Patients with a TT genotype had a significantly consumed C3 and C4 levels and higher anti-dsDNA positivity compared to those with GG and GT genotypes. Promoter polymorphism tended to be higher in juvenile-onset SLE cases.STAT4 (G/T) polymorphism was not associated with an increased risk of SLE in Egyptian females. However, vasculitis, photosensitivity and renal involvement were significantly higher among patients harboring the homomutant genotypes. Genetic polymorphism may be an important determinant affecting disease progression and is associated with DNA positivity and younger age of onset.

Genetic variation in CYP1A1 and AHRR genes increase the risk of systemic lupus erythematosus and exacerbate disease severity in smoker patients.

Genetic variations of aryl hydrocarbon receptor (AHR) pathway genes could influence the imbalanced immune response to xenobiotics. Therefore, we aimed to investigate the polymorphism of AHR pathway genes in systemic lupus erythematosus (SLE) patients in association with smoking. Genomic DNA from patients (N = 107) and controls (N = 105) of a population from northeast of Iran was used for genotyping of CYP1A1 T>C (rs4646903) and AHRR C>G (rs2292596) variants. The SLEDAI score and smoking status of the patients were registered. The AHR activity was estimated by CYP1A1 and CYP1B1 geneexpression in peripheral blood mononuclear cells (PBMC). The C allele in rs4646903 (odds ratio [OR] = 2.67) and G allele in rs2292596 (OR = 1.79) SNPs were significantly associated with the increased risk of SLE. The AHR pathway was more active in high-risk CYP1A1/AHRR: C/G haplotype. The most severe disease was observed in smoker patients with high-risk haplotype and both smoking (Exp (β) = 9.5) and high-risk CYP1A1/AHRR (C/G) haplotype (Exp (β) = 3.7) can significantly increase the likelihood of having severe (SLEDAI ≥ 20) SLE disease activity. Our findings indicated the association of xenobiotic-metabolizing genes (CYP1A1, AHRR) polymorphisms with the susceptibility to SLE and disease severity regarding the smoking background, suggesting the interaction of gene and environmental risk factors in SLE pathogenesis.

Suicide risk in systemic lupus erythematosus: A narrative review

Introduction: Despite the medical and scientific advances, the disease’s restrictions and the perception of personal and social losses related to its course reinforce fear and generate intense suffering in lupus patients. Psychiatric comorbidities, especially major depressive episodes, are highly prevalent during systemic lupus erythematosus. Among them, suicide is a behavior that is much more common than we believe.Objective: To perform a narrative review on suicidal behavior associated with systemic erythematosus lupus (SLE).Results: Studies have shown an increased risk of suicide among patients with chronic diseases and psychiatric disorders, especially depression. However, suicide cannot be attributed only to a higher prevalence of depression and other mental illnesses. Therefore, it is necessary to learn more about the suicide risk factors present in patients with lupus to work on secondary prevention and avoid the premature loss of lives and the additional suffering of families and surrounding communities. The coordination between the studies on suicidal behavior and its intricate network of individual and sociocultural factors and the studies on this multisystem autoimmune disease with a broad manifestation spectrum, lupus, creates new and essential field research.Conclusions: Non-psychiatrist office-based physicians, health clinics, or wards dedicated to the treatment of SLE should recognize and handle the suicide risk factors on their patients to reduce the suffering caused by this disease.