Systemic Lupus Erythematosus In Asians Research Articles

Genetic polymorphisms in genes involved in the type I interferon system (STAT4 and IRF5): association with Asian SLE patients.

Systemic lupus erythematosus (SLE) is a common autoimmune disease with a polymorphic clinical presentation involving multisystem damages with significant differences in prevalence and disease severity among different ethnic groups. Although genetic, hormonal, and environmental factors have been demonstrated to contribute a lot to SLE, the pathogenesis of SLE is still unknown. Numerous evidence revealed that gene variants within the type I interferons (IFN) signaling pathway performed the great genetic associations with autoimmune diseases including SLE. To date, through genome-wide association studies (GWAS), genetic association studies showed that more than 100 susceptibility genes have been linked to the pathogenesis of SLE, among which TYK2, STAT1, STAT4, and IRF5 are important molecules directly connected to the type I interferon signaling system. The review summarized the genetic associations and the detailed risk loci of STAT4 and IRF5 with Asian SLE patients, explored the genotype distributions associated with the main clinical manifestations of SLE, and sorted out the potential reasons for the differences in susceptibility in Asia and Europe. Moreover, the therapies targeting STAT4 and IRF5 were also evaluated in order to propose more personalized and targeted treatment plans in SLE.

Diagnostic performance of classification criteria for systemic lupus erythematosus: A validation study from Singapore.

Classification criteria for systemic lupus erythematosus (SLE) include American College of Rheumatology (ACR) 1997, Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) 2012 and European Alliance of Associations for Rheumatology (EULAR)/ACR 2019 criteria. Their performance in an Asian childhood-onset SLE (cSLE) population remains unclear as the clinical manifestations differ. We aim to evaluate the diagnostic performance in a cSLE cohort in Singapore. Cases were physician-diagnosed cSLE, while controls were children with mixed and undifferentiated connective tissue disease that posed an initial diagnostic challenge. Data were retrospec-tively reviewed to establish the 3 criteria fulfilled at diagnosis and over time. The study population included 120 cSLE cases and 36 controls. At diagnosis, 102 (85%) patients fulfilled all criteria. SLICC-2012 had the highest sensitivity (97.5%, 95% confidence interval [CI] 92.3-99.5), while ACR-1997 had the highest specificity (91.7%, 95% CI 77.5-98.3). All criteria had diagnostic accuracies at more than 85%. Over time, 113 (94%) fulfilled all criteria. SLICC-2012 remained the criteria with the highest sensitivity (99.2%, 95% CI 95.4-99.9), while ACR-1997 had the highest specificity (75.0%, 95% CI 57.8-87.9). Only SLICC-2012 and ACR-1997 had more than 85% diagnostic accuracy over time. Using a cutoff score of ≥13 for EULAR/ACR-2019 criteria resulted in improved diagnostic performance. SLICC-2012 criteria had the highest sensitivity early in the disease course in this first study evaluating the SLE classification criteria performance in a Southeast Asian cSLE cohort, while the ACR-1997 criteria had the highest specificity. Using a cutoff score of ≥13 for EULAR/ACR-2019 improved the diagnostic performance.

Associations of toll-like receptor polymorphisms with systemic lupus erythematosus: A meta-analysis

ObjectiveThe objective of this study was to examine whether polymorphisms in toll-like receptors 7 and 4 (TLR7 and 4) contribute to vulnerability to systemic lupus erythematosus (SLE). MethodsWe searched MEDLINE, Embase, and Web of Science for relevant articles and performed a meta-analysis to investigate the relationship between TLR7 rs179008, rs3853839, rs1790010, TLR4 rs4986791, and rs798690 polymorphisms and SLE. ResultsEighteen studies and 16 papers including 8022 patients with SLE and 9822 healthy controls were retrieved. Meta-analysis revealed that the TLR7 rs179008 T variant was not associated with SLE (OR = 1.008, 95% CI = 0.849–1.394, P = 0.504). Ethnic classification revealed no association between the TLR7 rs179008 T gene and SLE in either European or Latin American groups. Additionally, homozygous comparison, recessive, and dominant models revealed no association between the TLR7 rs179008 variant and SLE. In contrast, a significant association between SLE and the TLR7 rsrs3853839 GG + GA allele (OR = 2.135, 95% CI = 1.502–3.035, <0.001; OR = 23.20, 95% CI = 14.13–38.08, <0.001) was observed in the Arab and Asian groups. The T variant of TLR7 rsrs179010 was also associated with SLE in Asians (OR = 1.177, 95% CI = 1.048–1.321, P = 0.006). In contrast, the TLR4 rs4986791 variant was not associated with SLE in Europeans when allele, homozygous comparison, recessive, and dominant models were used. Furthermore, no association between the TLR4 rs4986790 variant and SLE risk in Europeans was found using any genomic model. ConclusionsMeta-analysis revealed that the TLR7 rs3853839 variant is associated with SLE risk in Asians and Arabs and that TLR7 rs179010 is associated with SLE in Asians. However, TLR7 rs179008, TLR4 rs4986791, and TLR rs798690 polymorphisms were not associated with SLE risk.

Plasma/Serum Oxidant Parameters in Systemic Lupus Erythematosus Patients: A Systematic Review and Meta-Analysis.

Most published results have revealed variations in the association of serum/plasma levels of malondialdehyde (MDA), apolipoprotein B (ApoB), and oxidized low-density lipoprotein (OxLDL) and systemic lupus erythematosus (SLE). This study was performed to establish MDA, ApoB, and OxLDL levels in systemic lupus erythematosus (SLE) patients. Electronic databases were searched for the included articles up to 27th February 2023. The meta-analysis included 48 articles with 2358 SLE patients and 2126 healthy controls considered for MDA, ApoB, and OxLDL levels. There were significantly higher MDA, ApoB, and OxLDL levels in SLE patients than those in the control groups. Subgroup analysis indicated that European/American SLE patients and patients of both ages <36 and ≥36 exhibited higher MDA, ApoB, and OxLDL levels. Arab and Asian SLE patients had higher ApoB and MDA/OxLDL levels. African SLE patients recorded higher OxLDL levels than the control groups. SLE patients with a body mass index (BMI) of ≥23 and a disease duration of <10 recorded significantly higher MDA, ApoB, and OxLDL levels. Patients with systemic lupus erythematosus disease activity index (SLEDAI) ≥8 of SLE had higher MDA and ApoB levels, whereas SLE patients with SLEDAI <8 showed significantly higher ApoB levels. Patients with BMI <23 of SLE had higher MDA and OxLDL levels. This study established significantly higher MDA, ApoB, and OxLDL levels in SLE patients, suggesting a possible role of MDA, ApoB, and OxLDL in the disease.

East-Asian lupus nephritis in the Hopkins Lupus Cohort.

East Asian systemic lupus erythematosus (SLE) is under represented in lupus cohorts outside of East Asia. We asked whether lupus nephritis was more common and more severe in East Asians than in other ethnicities in a large United States SLE cohort. The Hopkins Lupus Cohort, a longitudinal cohort of 2802 patients (53.5% Caucasian, 39.2% African-American, 3.2% East Asian) was studied. The SLICC/ACR Damage Index was used to assess renal outcomes. Results: East Asian patients had the same prevalence of lupus nephritis as African-Americans and both were higher than Caucasians. East Asians were not significantly different in frequency of end stage kidney disease compared with African-Americans. East Asians were more likely than Caucasians to have anti-Sm, low C3 and low C4. East Asians were more likely than African-Americans to have low C3 and low C4. East Asians living in the United States were more likely to have lupus nephritis than Caucasians. Poor outcomes such as end stage kidney disease occurred at an equal frequency in East Asians as in African-Americans. Lupus nephritis was both more frequent and more severe in East Asians than in African-Americans.

Effect of Belimumab on Preventing de novo Renal Lupus Flares

Belimumab was recently approved for treating lupus nephritis (LN), yet de novo LN cases during belimumab treatment given for nonrenal causes have been reported. Identification of reliable signals of impending flare is imperative. We evaluated belimumab efficacy in preventing de novo renal flares and factors associated with renal flare occurrence in nephritis-naïve patients with systemic lupus erythematosus (SLE) who are receiving add-on belimumab or placebo in 5 phase 3 clinical trials using Cox regression analysis. Of 1844 eligible patients, 136 (7.4%) developed a de novo renal flare during a 52-week long follow-up. Asian origin (Adjusted Hazard Ratio [HRadj]: 1.97; 95% confidence interval [CI]: 1.32-2.94; P= 0.001), positive baseline anti-double stranded DNA (anti-dsDNA) levels (HRadj: 1.32; 95% CI: 1.07-1.63; P= 0.008), and increasing mean prednisone dose during follow-up (HRadj: 1.03; 95% CI: 1.02-1.04; P< 0.001) were associated with de novo renal flares. Low-dose intravenous (IV) belimumab (1 mg/kg monthly) yielded a nearly 3-fold lower hazard of de novo renal flare (HRadj: 0.38; 95% CI: 0.20-0.73; P= 0.004). Subcutaneous (SC) belimumab (200 mg weekly) also yielded a lower hazard (HRadj.: 0.69; 95% CI: 0.54-0.88; P= 0.003). The labeled IV dose (10 mg/kg monthly) conferred no clear protection (HRadj.: 0.74; 95% CI: 0.50-1.09; P= 0.127). We corroborated the substantial vulnerability of the Asian SLE population to renal affliction. Add-on low-dose IV belimumab (1 mg/kg) and SC belimumab appeared protective against renal flares in nephritis-naïve patients with SLE. The approved IV dose (10 mg/kg) yielded no clear protection.

Systemic lupus erythematosus and toll-like receptor 9 polymorphisms: A meta-analysis of genetic association studies.

This study aimed to examine whether polymorphisms in toll-like receptor 9 (TLR9) contribute to vulnerability to systemic lupus erythematosus (SLE). We searched the MEDLINE, Embase, and Web of Science databases for relevant articles. We conducted a meta-analysis to examine the association between the TLR9 rs187084, rs352139, rs352140, and rs5743836 polymorphisms and SLE risk. A total of 5447 patients with SLE and 6588 control participants across 26 trials from 24 articles were included. The TLR9 rs187084 T allele was significantly associated with SLE (odds ratio, 1.146; 95% confidence interval, 1.033-1.273; p = 0.010). In a meta-analysis, the TLR9 rs187084 T allele was associated with SLE in the Asian population but not in the Arab population, demonstrating the existence of ethnicity-specific effects. Using homozygote contrast and recessive models, the researchers also found that the TLR9 rs187084 T/C polymorphism was associated with SLE. The TLR9 rs352139 G allele was not associated with SLE in this meta-analysis. After accounting for ethnic differences, we found that the TLR9 rs352139 G allele was not associated with SLE in Asians and Arabs. Furthermore, homozygote contrast and dominant models found no association between the TLR9 rs352139 G/A polymorphism and SLE. TLR9 polymorphisms at rs352140 and rs5743836 were not associated with an increased risk of SLE in any genetic prediction model, including people of Asian, European, or Latin American ancestry. SLE susceptibility is associated with the TLR9 rs187084 polymorphism in the Asian population and the rs187084, rs352139, rs352140, and rs5743836 polymorphisms in the Asian, European, and Latin American populations, respectively.

Non-leaking cystoid macular edema and bull’s eye maculopathy caused by hydroxychloroquine toxicity in Asian patients

Introduction: Hydroxychloroquine (HCQ) is used for treating systemic lupus erythematosus (SLE). It can cause irreversible toxic retinopathy, we discuss the outcome of HCQ retinopathy and emphasize the distinct toxicity pattern in Asian patients. Case Series: We report a retrospective case series of two systemic lupus erythematosus (SLE) patients who presented with HCQ toxicity. Both Asian SLE patients were treated with HCQ over five years with cumulative dose of &gt;1000 g. Both had characteristic findings on spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). First patient had non-leaking cystoid macula edema (CME) associated with HCQ retinopathy and second patient had bull’s eye maculopathy (BEM). They exhibited different outcome after drug cessation. There was no disease progression in former whereas latter lost her central vision over two years. Conclusion: Non-leaking CME is rare and can be a sequence of HCQ retinopathy. Bull’s eye maculopathy is another manifestation of severe HCQ toxicity. Toxic damage to retina is irreversible, and may progress even after the drug is stopped, so is crucial to discontinue once toxicity is detected. Patients on HCQ warrant annual screening with multimodal imaging. There are racial differences in HCQ toxicity, hence distinct screening tests should be performed in Asian population.

Differential impact of disease activity and damage on health-related quality of life in patients with systemic lupus erythematosus.

To study the association between disease activity, disease-related organ damage and health-related quality of life (HRQoL) among Asian patients with systemic lupus erythematosus (SLE). We prospectively recruited adult SLE patients from a single tertiary center and followed them three-monthly. We recorded the SLE Disease Activity Index 2000 (SLEDAI-2K) at each visit. SLICC-ACR damage index (SDI) and HRQoL (Medical Outcomes Survey Short Form 36 (SF-36)) were recorded annually. We evaluated the association between SLEDAI-2K and SDI with SF-36 physical (PCS) and mental (MCS) component scores using linear mixed effect models. We studied 198 patients, comprising Chinese, Malays and Indians. The mean (SD) age at enrollment was 47.1 (12.5) years. The baseline median (IQR) SLEDAI-2k was 2 (0-4). While the mean PCS improved significantly in the second and third year, MCS was unchanged. In the multivariable mixed model analysis, SDI, but not SLEDAI-2k, was significantly associated with poorer PCS (estimate of coefficient (SE) -0.81 (0.29), p < .01). Conversely, SLEDAI-2k, but not SDI, was negatively associated with MCS (estimate of coefficient (SE) -0.36 (0.17), p = .04). In this cohort of multi-ethnic Asian SLE patients, disease activity is associated with poorer mental, but not physical, HRQoL; whereas disease-related damage is associated with poorer physical, but not mental HRQoL. Our findings suggest a need to differentially approach the impaired HRQoL in SLE patients at different phases of disease; possibly by treating disease activity in patients with impaired mental HRQoL and addressing disease-related damage in patients with impaired physical functioning.

Identification of Shared and Asian-Specific Loci for Systemic Lupus Erythematosus and Evidence for Roles of Type III Interferon Signaling and Lysosomal Function in the Disease: A Multi-Ancestral Genome-Wide Association Study.

Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease with differences in prevalence and severity among ancestral groups. This study was undertaken to identify novel genetic components, either shared by or distinct between Asian and European populations. Both trans-ancestral and ancestry-specific meta-analyses of genome-wide association studies (GWAS) for SLE were performed, involving 30,604 participants of European, Chinese, or Thai origin. Using public epigenomic data and expression quantitative trait loci, fine-mapping analyses were conducted to identify putative causal variants and genes for the newly identified loci. Performance of polygenic risk scores for the Thai cohort was evaluated by comparing different training data. A 1-bp deletion upstream of IFNLR1 was found to be associated with SLE, with the risk allele correlated with increased expression of IFNLR1. This gene encodes interferon-λ (IFNλ) receptor 1, providing evidence of a role of type III IFN signaling in SLE. An intronic variant in SLC29A3 was found to be associated with SLE in Asians only. The putative risk variant may modulate SLC29A3 expression in a monocyte-specific manner. SLC29A3 encodes a lysosomal nucleoside transporter, and subsequent analyses suggested that reduced lysosomal function and phagocytosis might be the mechanism underlying this association. Ancestry-shared loci in or near TAOK3, CHD9, CAMK1D, ATXN1, and TARBP1 and Asian-specific loci close to PEX2, FCHSD2, and TMEM116 also reached the genome-wide significant association with SLE. In addition, trans-ancestral meta-analysis was shown to be valuable in risk prediction for individuals without ancestry-matched data. In this study both shared and Asian-specific loci for SLE were identified, and functional annotation provided evidence of the involvement of increased type III IFN signaling and reduced lysosomal function in SLE.

POS-137 LONG TERM RENAL AND PATIENT SURVIVAL IN LUPUS NEPHRITIS PATIENT TREATED IN UKKMC MALAYSIA

Lupus nephritis (LN) is one of severe organ manifestation and affects 60% of patients with systemic lupus erythematosus (SLE). Asian and Non-Caucasian SLE patients were reported to have worse outcomes. Ten percent of LN progress to end stage renal disease (ESRD) and their life expectancy was reduced by 23.7 years compared to the general population. This study was aimed to look at the long term renal and patients’ survival in LN patients treated at our center.

5-Year Progressive Bull's Eye Maculopathy Despite Cessation of Hydroxychloroquine in Asian Systemic Lupus Erythematosus Lady

A 57-year-old systemic lupus erythematosus Chinese lady with maintenance hydroxychloroquine (HCQ) therapy of 200mg daily for 21years was weighed 61.5 kg-67.7 kg (mean 65.6 kg) throughout [1]. Regular ophthalmological tests in past decades first revealed subtle retinal pigment epithelium (RPE) changes, simulating early pericentral retinopathy pattern, on 2014’s fundus autofluorescence photos (Figure-1), and HCQ was immediately stopped [2,3]. Bull’s eye maculopathy was progressing inferiorly (Figure-2), to a combined parafoveal and pericentral retinopathy pattern (Figure-3), eventually generalized RPE atrophy (Figure-4) [3,4]. Safety HCQ dosage is 5mg/kg/day, yet retinal toxicity risk increases with consumption duration [1]. Maculopathy could progress after cessation of HCQ, given its long half-life of >1month [5].

Associations between Polymorphisms in the IL-1 Gene and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus: Evidence from a Meta-Analysis

Background: Previous studies on polymorphisms in interleukin-1 (IL-1) and the risk of rheumatoid arthritis (RA)/systemic lupus erythematosus (SLE) yielded inconsistent results. Objectives: The authors performed this meta-analysis to more robustly evaluate associations between polymorphisms in the IL-1 gene and the risk of RA/SLE. Methods: MEDLINE, Embase, Web of Science, Wanfang, VIP, and CNKI were systematically searched for eligible studies, and 34 relevant studies were finally selected to be eligible for inclusion. Results: We found that IL-1A +4845G/T polymorphism was significantly associated with the risk of RA in the overall population (dominant comparison: p = 0.02; overdominant comparison: p = 0.05; allele comparison: p = 0.04), whereas IL-1B +3954C/T polymorphism was significantly associated with the risk of RA in the overall population (overdominant comparison: p = 0.03; allele comparison: p = 0.01) and Asians (recessive comparison: p = 0.007; allele comparison: p = 0.002). In addition, we found that IL-1A –889C/T polymorphism was significantly associated with the risk of SLE in Caucasians (allele comparison: p = 0.04), IL-1B –31T/C polymorphism was significantly associated with the risk of SLE in the overall population (recessive comparison: p = 0.04), and IL-1B –511C/T polymorphism was significantly associated with the risk of SLE in Asians (recessive comparison: p = 0.01; allele comparison: p = 0.03). Conclusions: This meta-analysis suggests that IL-1A +4845G/T and IL-1B +3954C/T polymorphisms may influence the risk of RA, whereas IL-1A –889C/T, IL-1B –31T/C, and IL-1B –511C/T polymorphisms may influence the risk of SLE.

Association of MBL2 gene polymorphisms and systemic lupus erythematosus susceptibility: A meta-analysis.

Mannose binding lectin (MBL) gene single nucleotide polymorphisms have been associated with systemic lupus erythematosus (SLE) risk with inconsistent results. This study aimed to explore whether MBL2 A\B, A\C, A\D, A\O, L\H and Y\X polymorphisms affected SLE susceptibility. A meta-analysis was performed on 20 studies, containing allelic contrast, additive, dominant and recessive models. Odds ratio (OR) was calculated to reflect the effect of association. A total of 64 pooled comparisons were conducted, including 7194 SLE patients and 7401 healthy controls. The meta-analysis inducted a significant association between allele B and SLE (OR=0.766, 95% CI=0.681-0.862, P<.001). The genotype BB in the additive model and AB+BB in the recessive model both reduced the risk of SLE (OR=0.611, 95% CI=0.422-0.882, P=.009; OR=0.806, 95% CI=0.688-0.944, P=.008). Regarding A\O polymorphisms, results revealed statistical differences in allelic contrast, additive model and recessive models (OR=0.826, 95% CI=0.732-0.931, P=.002; OR=0.737, 95% CI=0.557-0.977, P=.034 and OR=0.793, 95% CI=0.683-0.921, P=.002, respectively). As for L\H, meta-analysis revealed that allele H and genotype HH both decreased SLE susceptibility in allelic contrast and dominant models (OR=1.463, 95% CI=1.097-2.007, P=.018; OR=1.383, 95% CI=1.124-1.701, P=.002). Stratification by ethnicity indicated that allele H related to SLE in European populations (OR=0.736, 95% CI=0.617-0.879, P=.001), and the recessive model correlated with SLE in Asians (OR=0.808, 95% CI=0.667-0.979, P=.03). The present study suggests that A\B and A\O polymorphisms were associated with SLE susceptibility, and the allele H may be a protective factor in SLE.

Relationship between disease activity, organ damage and health-related quality of life in patients with systemic lupus erythematosus: A systemic review and meta-analysis.

Systemic lupus erythematosus (SLE) is a common systemic autoimmune disease that may lead to considerable physical, psychological, and socioeconomical burden. In previous studies, inconsistent results were reported for the association of disease activity and organ damage with health-related quality of life (HRQoL). This paper aimed to explore the relationship between disease activity, organ damage, and HRQoL measured by SF-36, EQ-5D, LupusQoL, and LupusPRO and investigate whether the correlation is region-specific. We systematically searched for studies reporting the association between SLE disease activity, organ damage, and HRQoL in MEDLINE, EMBASE, PsycINFO, World of Science, the Cochrane Library, and CINAHL from inception to December 2019. A meta-analysis and region subgroup analysis were performed with a random-effects model to estimate pooled correlation coefficients and heterogeneity. Forty articles were included representing of 6079 adult SLE patients. The meta-analysis of SF-36 and LupusPRO studies revealed mild to moderate negative correlations between disease activity and domains of these HRQoL measurements (correlation coefficient r ranging from -0.27 to -0.07). Likewise, negative correlations were found between organ damage and domains of SF-36 and LupusPRO (r ranging from -0.25 to -0.08). The pooled correlation coefficient is relatively higher in physical functioning related domains than mental health. In the region subgroup analysis, disease activity had strong negative correlations with SF-36 domains in African and European SLE patients, while organ damage had the strongest negative correlation with SF-36 domains in Asian SLE patients (p<0.010). This study provides the first comprehensive assessment of the relationship between disease activity, organ damage, and four popular HRQoL instruments, which provides useful insight into the target therapy in SLE management.

Association Between Signal Transducers and Activators of Transcription 4 rs7574865 Polymorphism and Systemic Lupus Erythematosus: A Meta-analysis

Objective. The purpose of this study was to determine whether the rs7574865 polymorphism of signal transducers and transcription 4 activators (STAT4) in multiple ethnic populations is associated with susceptibility to systemic lupus erythematosus (SLE). Methods. A meta-analysis on the STAT4 T allele rs7574865 polymorphism was performed in all subjects of study as well as in each ethnic population. Results. It included twenty-four manuscripts with 36 comparative studies of 22,898 SLE patients and 24,838 controls. The mean frequency of the STAT4 rs7574865 T allele was 28.5%, ranging from 14.3% to 35.7%, among the controls. T allele rates were 14.3%, 22.8%, 31.9%, 32.4%, and 35.7%, respectively in African American, European, Arab, Asian, and Latin American populations. Meta-analysis revealed a substantial correlation in all subjects between STAT4 rs7574865 and SLE (odds ratio=1.549, 95% confidence interval=1.459∼1.644, p＜0.001). Analysis after stratification of race showed a strong association between the STAT4 rs7574865 T allele and SLE in Europeans, Asians, Latin Americans, African Americans, and Arabs. Conclusion. This meta-analysis demonstrated that the STAT4 rs7574865 polymorphism in different ethnic groups was correlated with SLE susceptibility, and that its prevalence depended on ethnicity. (J Rheum Dis 2020;27:277-284)

TNFSF4 is a risk factor to systemic lupus erythematosus in a Latin American population.

The aim of this study was to examine the association of three TNFSF4 single nucleotide variants (SNVs) with systemic lupus erythematosus (SLE) susceptibility in Mexican patients. Genotypes of the TNFSF4 rs1234315T/C, rs2205960G/T, and rs704840T/G SNVs were determined using a TaqMan assay. In our study, we included 395 patients with SLE and 500 controls. Our information shows a significant difference in the allelic and genotypic frequency of the three TNFSF4 SNVs between cases and controls. Thus, our data showed an association between TNFSF4 rs1234315T/C (T vs. C, OR 1.40, p = 0.00087), rs2205960G/T (G vs. T, OR 1.32, p = 0.0037), and rs704840T/G (T vs. G, OR 1.41, p = 0.0003) and SLE susceptibility in Mexican subjects. Besides, we conducted a meta-analysis to determine the role of TNFSF4 rs2205960G/T and SLE susceptibility; our results showed that this variant is a risk factor for SLE in Latin Americans and Asians. Our results show that TNFSF4 rs1234315T/C, rs2205960G/T, and rs704840T/G are risk factors to SLE in Mexicans. This is the first study to document an association between TNFSF4 rs704840T/G and SLE in a Latin American population. In addition, our meta-analysis showed that TNFSF4 rs2205960G/T is a risk factor for Asians and Latin Americans. Key Point • The TNFSF4 rs1234315T/C, rs2205960G/T, and rs704849T/G SNVs are risk factors to SLE in patients from Mexico.

Association of HLA-G polymorphisms with systemic lupus erythematosus and correlation between soluble HLA‑G levels and the disease: ameta-analysis.

To investigate the association between HLA‑G polymorphisms and systemic lupus erythematosus (SLE) susceptibility as well as the relationship between circulating soluble HLA‑G (sHLA‑G) levels and SLE. Ameta-analysis was performed to investigate the relationships between HLA‑G 14-bp insertion(I)/deletion(D), +3142 G/C, +3035 T/C, and +3003 C/T polymorphisms and SLE as well as the relationship between sHLA‑G serum/plasma levels in SLE patients and controls. Eleven publications fulfilled our inclusion criteria. Meta-analysis under the dominant model showed an association in the overall group between the II+ID genotype of HLA‑G 14-bp I/D polymorphism and SLE (OR = 1.213, 95%CI = 1.077-1.365, P = 0.001). Ethnicity-specific meta-analysis showed an association between II+ID and SLE in Asians but not in South American and European populations. No correlation was observed using the allele contrast between HLA‑G +3142 G/C polymorphisms and SLE. Contrastingly, +3035 T/C and +3003 C/T meta-analysis showed asignificant allelic association between SLE and HLA‑G polymorphisms (OR = 1.378, 95%CI = 1.109-1.713, P = 0.004; OR = 1.834, 95%CI = 1.112-3.022, P = 0.017; respectively). sHLA‑G levels were significantly higher in the SLE group than in the controls (SMD = 0.637, 95%CI = 0.382-0.892, P < 0.001). We showed association of HLA‑G 14-bp I/D, +3035 T/C, and +3003 C/T polymorphisms with SLE susceptibility and significantly higher circulating sHLA‑G levels in SLE patients.

Maternal and perinatal outcomes of pregnancies in systemic lupus erythematosus: A nationwide population-based study

Objectives: Systemic lupus erythematosus (SLE) is an autoimmune disease that develops mainly in women of reproductive age. We aimed to explore the risk of pregnancy complications in Asian patients with SLE.Methods: From January 2005 to December 2014, we conducted a nationwide case-control study, using Taiwan's National Health Insurance Research Database. Obstetric complications and perinatal outcomes in SLE patients were compared with those without SLE.Results: 2059 SLE offspring and 8236 age-matched, maternal healthy controls were enrolled. We found increased obstetric and perinatal complications in SLE population compared with healthy controls. SLE patients exhibited increased risk of preeclampsia/eclampsia (8.98% vs.1.98%, odds ratio [OR]: 3.87, 95% confidence interval [95% CI]: 3.08–4.87, p<0.0001). Their offspring tended to have lower Apgar scores (<7) at both 1 min (10.7% vs. 2.58%, p<0.0001) and 5 min (4.25% vs. 1.17%, p<0.0001), as well as higher rates of intrauterine growth restriction (IUGR, 9.91% vs. 4.12%, OR: 2.24, 95% CI: 1.85–2.71, p<0.0001), preterm birth (23.70% vs 7.56%, OR: 3.00, 95% CI: 2.61–3.45, p<0.0001), and stillbirth (4.23% vs. 0.87%, OR: 3.59, 95% CI: 2.54–5.06, p<0.0001). The risks of preterm birth and stillbirth were markedly increased in SLE patients with concomitant preeclampsia/eclampsia or IUGR. Preterm birth of SLE patients was 1~4 gestational weeks earlier than that of healthy controls and the peak occurrence of stillbirth in SLE population was at 20~30 gestational weeks.Conclusions: Asian SLE patients exhibited increased risks of maternal complications and adverse birth outcomes. Frequent antenatal visits before 20 gestational weeks are recommended in high-risk SLE patients.

Elevated Circulating Interleukin-17 Levels in Patients with Systemic Lupus Erythematosus: A Meta-analysis

ABSTRACT Background Previous studies concerning the circulating interleukin-17 (IL-17) in systemic lupus erythematosus (SLE) were contradictory. Aims To further precisely investigate circulating IL-17 in SLE and evaluate its influential factors by meta-analysis. Methods EMBASE, PubMed and Cochrane Library were comprehensively searched to obtain studies on circulating IL-17 in SLE patients by November 22, 2018. The results were illustrated by pooled standard mean difference (SMD) with corresponding 95% confidence interval (CI) using random-effects model as there was significant heterogeneity, which was estimated using Cochran Q and I2 statistics. Subgroup analyses and sensitivity analyses were also conducted. Results Overall, 1872 articles were reviewed and 20 studies involving 1067 subjects with SLE and 721 healthy controls (HCs) were enrolled in the final analysis according to inclusion criteria. Compared with HCs, circulating IL-17 levels in SLE patients were elevated (SMD: 1.183, 95% CI: 0.763–1.603; P < .001). Moreover, in comparison to HCs, European and Asian SLE patients, age <30 years, disease duration ≥5 years, NOS scores <7 and using ELISA showed increased circulating IL-17 status, whereas no significant change was observed in other subgroups. There was no significant publication bias. Sensitivity analyses demonstrated that the results of our meta-analysis were robust. Conclusions SLE patients have higher circulating IL-17 levels, which is influenced by ethnic, age and disease duration, literature quality and measurements.