scholarly journals Impact of IL-10 gene polymorphisms and its interaction with environment on susceptibility to systemic lupus erythematosus

2020 ◽  
Vol 34 ◽  
pp. 205873842094591
Author(s):  
Gui-Hong Wang ◽  
Ting Zuo ◽  
Zheng-Cai Zuo

This study aims to explore the impact of interleukin (IL)-10 single nucleotide polymorphisms (SNPs) and its interaction with environment on the risk of systemic lupus erythematosus (SLE). Chi-square testing method was used to investigate whether the distributions for genotype of four SNPs were differed from Hardy-Weinberg equilibrium (HWE). Logistic regression was used to test the association between IL-10 SNPs and SLE risk. The best interaction combinations between IL-10 SNPs and environmental factors were assessed by generalized multifactor dimensionality reduction (GMDR). Both rs1800896-G and rs1800871-T alleles were associated with increased risk of SLE, the odds ratios (ORs) (95% confidence interval (CI)) for the two SNPs were 1.68 (1.25–2.09) and 1.47 (1.12–1.94), respectively. Then, we used the GMDR method to analyze the high-order interactions of four SNPs within IL-10 gene and environmental factors on SLE risk. We found a significant interaction combination (two-locus model with P = 0.001) between rs1800896 and smoking, after adjusting for gender, age, body mass index (BMI), and alcohol drinking. We also used two-variable stratified analysis by logistic regression to analyze the synergistic effect between two variables (rs1800896 and smoking), which had significant significance in GMDR model. We found that current smokers with rs1800896-AG or GG genotype have the highest SLE risk, compared with never smokers with the rs1800896-AA genotype, OR (95% CI) = 2.24 (1.52–3.58). The rs1800896-G and rs1800871-T alleles and interaction between rs1800896 and current smoking were all associated with increased risk of SLE.

2021 ◽  
Vol 61 (1) ◽  
Author(s):  
Yu Fu ◽  
Qing Lin ◽  
Zhi-rong Zhang

Abstract Objective To more precisely estimate the association between the tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene polymorphisms and systemic lupus erythematosus (SLE) susceptibility, we performed a meta-analysis on the association of the following single nucleotide polymorphisms (SNPs) of TNFSF4 with SLE: rs1234315, rs844648, rs2205960, rs704840, rs844644, rs10489265. Methods A literature-based search was conducted using PubMed, MEDLINE, Embase, Web of Science databases, and Cochrane Library databases to identify all relevant studies. And the association of TNFSF4 gene polymorphisms and SLE susceptibility was evaluated by pooled odds ratio (OR) with 95% confidence interval (CI). Results The meta-analysis produced overall OR of 1.42 (95% CI 1.36–1.49, P < 0.00001), 1.41 (95% CI 1.36–1.46, P < 0.00001) and 1.34 (95% CI 1.26–1.42, P < 0.00001) for the rs2205960, rs1234315 and rs704840 polymorphisms respectively, confirming these three SNPs confer a significant risk for the development of SLE. On the other hand, the meta-analysis produced overall OR of 0.92 (95% CI 0.70–1.21, P = 0.54) for the rs844644 polymorphism, suggesting no significant association. And no association was also found between either rs844648 1.11 (OR 1.11, 95% CI 0.86–1.43, P = 0.41) or rs10489265 (OR 1.17, 95% CI 0.94–1.47, P = 0.17) polymorphism with SLE susceptibility, respectively. Conclusions Our meta-analysis demonstrated that the TNFSF4 rs2205960, rs1234315 and rs844840 SNPs was significantly associated with an increased risk of SLE.


Lupus ◽  
2021 ◽  
pp. 096120332110423
Author(s):  
Zeinab R Attia ◽  
Mohamed M Zedan ◽  
Thuraya M Mutawi ◽  
Entsar A Saad ◽  
Mohamed A El Basuni

Objectives Our purpose was to investigate, for the first time, genotypes and alleles distribution of two single nucleotide polymorphisms (SNPs) of interleukin 22 (IL-22) (rs1012356 and rs2227485) in Egyptian pediatric and adolescents with systemic lupus erythematosus (SLE) and to evaluate the plasma IL-22 levels and their association with gene polymorphism and SLE risk and severity. Methods The TaqMan™ SNP genotyping assay on a real-time polymerase chain reaction (PCR) system was employed to evaluate the polymorphism’s genotypes. Plasma IL-22 levels were determined by using an enzyme-linked immunoabsorbent assay (ELISA). Results The frequencies and genotypes of rs2227485 and rs1012356 in IL-22 between SLE patients and controls also haplotypes formed by the same SNPs revealed no statistically significant difference ( p > 0.05). Otherwise, logistic regression analysis revealed that patients carrying rs1012356 “TA + AA” genotype had increased risk for prediction of SLE activity (OR = 1.610, 95% CI = 1.339–2.760, p = 0.034) by lowering plasma IL-22 level. Conclusions Among Egyptian pediatric and adolescents, we confirm a combined model “TA + AA” in rs1012356 (A/T) of IL-22 in regression analysis, as an independent predictor for SLE activity by lowering IL-22 plasma levels. Despite neither SNP rs2227485 A/G in IL-22 gene nor haplotypes formed by the same two SNPs (rs2227485 A/G and rs1012356 A/T) were significantly associated with the clinical and/or laboratory manifestations of SLE.


2021 ◽  
Vol 10 (17) ◽  
pp. 3842
Author(s):  
René Cordtz ◽  
Salome Kristensen ◽  
Louise Plank Holm Dalgaard ◽  
Rasmus Westermann ◽  
Kirsten Duch ◽  
...  

Background: Patients with systemic lupus erythematosus (SLE) have an increased risk of infections due to impaired immune functions, disease activity, and treatment. This study investigated the impact of having SLE on the incidence of hospitalisation with COVID-19 infection. Methods: This was a nationwide cohort study from Denmark between 1 March 2020 to 2 February 2021, based on the linkage of several nationwide registers. The adjusted incidence of COVID-19 hospitalisation was estimated for patients with SLE compared with the general population in Cox-regression models. Among SLE patients, the hazard ratio (HR) for hospitalisation was analysed as nested case-control study. Results: Sixteen of the 2533 SLE patients were hospitalised with COVID-19 infection. The age-sex adjusted rate per 1000 person years was 6.16 (95% CI 3.76–10.08) in SLE patients, and the corresponding hazard ratio was 2.54 (95% CI 1.55–4.16) compared with the matched general population group after adjustment for comorbidities. Among SLE patients, hydroxychloroquine treatment was associated with a HR for hospitalisation of 0.61 (95% CI 0.19–1.88), and 1.06 (95% CI 0.3–3.72) for glucocorticoid treatment. Conclusion: Patients with SLE were at increased risk of hospitalisation with COVID-19.


2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Peng Wang ◽  
Lei Liu ◽  
Li-Fang Zhao ◽  
Chan-Na Zhao ◽  
Yan-Mei Mao ◽  
...  

Objectives. This study was to investigate the association of melatonin (MTN) pathway gene’s single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE). Methods. We recruited 495 SLE patients and 493 healthy controls, 11 tag SNPs in MTN receptor 1a (MTNR1a), MTNR1b, and arylalkylamine N-acetyltransferase (AANAT) genes were genotyped and analyzed. Serum MTN concentration was determined by enzyme-linked immunosorbent assay (ELISA) kits. Results. Two SNPs of AANAT gene (rs8150 and rs3760138) associated with the risk of SLE; CC carriers of rs8150 had a lower risk as compared to GG (OR=0.537, 95% CI: 0.361, 0.799), whereas GG carrier in rs3760138 had an increased risk (OR=1.823, 95% CI: 1.154, 2.880) compared to TT. However, we did not find any genetic association between the other nine SNPs with SLE risk. Case-only analysis showed associations of rs2165667 and rs1562444 with arthritis, rs10830962 with malar rash, rs3760138 with immunological abnormality, and rs8150 with hematological abnormality. Furthermore, a significant difference between plasma MTN levels with different genotypes of rs1562444 was observed. Haplotype analyses revealed that haplotype of CCTAT, CTAGT, and GGG was significantly associated with the increased risk in SLE susceptibility, but TCTAT and CTG appeared to be a protective haplotype. Conclusions. The present study supported the genetic association of MTN pathway genes with SLE susceptibility and specific clinical manifestations, suggesting the potential role of MTN pathway genes in the pathogenesis and development of SLE.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 636.1-636
Author(s):  
Y. Santamaria-Alza ◽  
J. Sanchez-Bautista ◽  
T. Urrego Callejas ◽  
J. Moreno ◽  
F. Jaimes ◽  
...  

Background:The most common complication in patients with SLE is infection, and its clinical presentation is often indistinguishable from SLE flares. Therefore, laboratory ratios have been evaluated to differentiate between those events. Among them, ESR/CRP1, neutrophil/lymphocyte (NLR)2, and platelet/lymphocyte (PLR)3 ratios have been previously assessed with acceptable performance; however, there is no validation of those ratios in our SLE population.Objectives:To examine the predictive capacity of infection of the lymphocyte/C4 (LC4R), lymphocyte/C3 (LC3R), and ferritin/ESR (FER) ratios in SLE patients, and to evaluate the performance of ESR/CRP, NLR, AND PLR ratios in our SLE population.Methods:We conducted a cross-sectional study of SLE patients admitted to the emergency service at Hospital San Vicente Fundación (HSVF). The HSVF ethics committee approved the execution of the project.Patients were categorized into four groups according to the main cause of hospitalization: (1) infection, (2) flare, (3) infection and flare and, (4) neither infection nor flare.We calculated the median values of the ratios and their respective interquartile ranges for each group. Then, we compared those summary measures using the Kruskal-Wallis test. Subsequently, we assessed the predictive capacity of infection of each ratio using ROC curve. Finally, we carried out a logistic regression model.Results:A total of 246 patients were included, among them 90.7% were women. The median age was 28 years (IQR: 20-35 years). Regarding the outcomes, 37.0% of the patients had flares, 30.9% had neither infection nor flare, 16.7% had an infection and, 15.5% had simultaneously infection and flare. When compared the four groups, statistical significance (p<0.05) was observed. Area under the ROC curve (AUC) for infection prediction was as follows: 0.752 (sensitivity 60.5%, specificity 80.5%) for LC4R, 0.740 (sensitivity 73.2%, specificity 68.3%) for FER, 0.731 (sensitivity 77.6%, specificity 80.5%) for LC3R.In the logistic regression modeling, we observed that an increase in the risk of infection was associated with an LC4R below 66.7 (OR: 6.3, CI: 2.7 – 14.3, p <0.0001), a FER greater than 13.6 (OR: 5.9, CI: 2.8 – 12.1, p <0.0001) and an LC3R below 11.2 (OR: 4.9, CI: 2.4 – 9.8, p <0.0001).The ESR/CRP and PLR performed poorly with an AUC of 0.580 and 0.655, respectively. In contrast, the NLR showed better performance (AUC of 0.709, with a sensitivity of 80.2% and specificity of 55.7%).Figure 1.ROC curves of the evaluated ratiosConclusion:These laboratory ratios could be easy to assay and inexpensive biomarkers to differentiate between infection and activity in SLE patients. The LC4R, FER, and LC3R have a significant diagnostic performance for detecting infection among SLE patients. Of the ratios previously evaluated, ESR/CRP, LPR, NLR, only the latest has an adequate performance in our population.References:[1]Littlejohn E, Marder W, Lewis E, et al. The ratio of erythrocyte sedimentation rate to C-reactive protein is useful in distinguishing infection from flare in systemic lupus erythematosus patients presenting with fever. Lupus. 2018;27(7):1123-1129.[2]Broca-Garcia BE, Saavedra MA, Martínez-Bencomo MA, et al. Utility of neutrophil-to-lymphocyte ratio plus C-reactive protein for infection in systemic lupus erythematosus. Lupus. 2019;28(2):217-222.[3]Soliman WM, Sherif NM, Ghanima IM, EL-Badawy MA. Neutrophil to lymphocyte and platelet to lymphocyte ratios in systemic lupus erythematosus: Relation with disease activity and lupus nephritis. Reumatol Clin. 2020;16(4):255-261s.Disclosure of Interests:None declared


Author(s):  
Eman M. Khedr ◽  
Rania M. Gamal ◽  
Sounia M. Rashad ◽  
Mary Yacoub ◽  
Gellan K. Ahmed

Abstract Background Depression is common in systemic lupus erythematosus (SLE) and is an unmeasured risk factor, yet its symptoms can be neglected in standard disease evaluations. The purpose of this study was to assess the frequency and the impact of depression on quality of life in SLE patients. We recruited 32 patients with SLE and 15 healthy control volunteers in the study. The following investigations were undertaken in each patient: clinical and rheumatologic assessment, SLE Disease Activity Index-2k (SLEDAI-2k), Beck Depression Inventory (BDI), Short-Form Health Survey (SF-36) questionnaire, and routine laboratory tests. Results There was a high percentage of depression (46.9%) in the SLE patients. Regarding quality of life (SF-36), there were significant affection of the physical and mental composite summary domains (PCS and MCS) scores in lupus patients compared with controls (P < 0.000 for both) with the same significant in depressed compared with non-depressed patients. SF-36 subscales (physical function, limit emotional, emotional wellbeing, and social function) were significantly affected in depressed lupus patients compared with non-depressed patients. There was a significant negative correlation between the score of MCS domain of SF-36 with BDI (P < 0.000) while positive correlation between SLEDAI score with depression score. In contrast, there were no significant correlations between MCS or PCS with age, duration of illness, or SLEDAI-2K. Conclusions Depression is common in SLE patients and had a negative impact on quality of life particularly on MCS domain and positive correlation with disease severity score. Trial registration This study was registered on clinical trial with registration number: NCT03165682 https://clinicaltrials.gov/ct2/show/NCT03165682 on 24 May 2017.


Lupus ◽  
2021 ◽  
pp. 096120332110047
Author(s):  
Ibrahim Almaghlouth ◽  
Sindhu R Johnson ◽  
Eleanor Pullenayegum ◽  
Dafna Gladman ◽  
Murray Urowitz

Immunoglobulins play a fundamental role in the protection of the human body against internal and external threats. They also contribute to the immune system homeostasis and maintenance of self-tolerance. Hypogammaglobulinemia is occasionally encountered in routine clinical practice by rheumatologists. Low levels of immunoglobulins can occur as primary or secondary issues and may predispose patients to various forms of infection. However, the impact of the low immunoglobulin level abnormality varies with the underlying condition. In this narrative review, we shed light on the overall types and functions of immunoglobulins for clinicians. We discuss important principles of immunoglobulin measurements. We then consider the primary and secondary causes of low immunoglobulins with a special focus on hypogammaglobulinemia in patients with systemic lupus erythematosus (SLE).


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarfaraz A. Hasni ◽  
Sarthak Gupta ◽  
Michael Davis ◽  
Elaine Poncio ◽  
Yenealem Temesgen-Oyelakin ◽  
...  

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


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