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

Objective: The 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). Methods: We 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. Results: Eighteen 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. Conclusions: Meta-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.

Intra-articular injection of stigmasterol-loaded nanoparticles reduce pain and inhibit the inflammation and joint destruction in osteoarthritis rat model: A pilot study.

Stigmasterol, a plant-derived sterol, sharing structural similarity with cholesterol, has demonstrated anti-osteoarthritis (OA) properties, attributed to its antioxidant and anti-inflammatory capabilities. Given that OA often arises in weight bearing or overused joints, prolonged localized treatment effectively targets inflammatory aspects of the disease. This research explored the impact of stigmasterol-loaded nanoparticles delivered via intra-articular injections in an OA rat model. Employing mesoporous silica nanomaterials (MSNs) combined with ß-cyclodextrin (ß-CD) as a vehicle, stigmasterol was loaded in conjunction with tannic acid, forming stigmasterol/ß-CD-MSNs to facilitate a sustained stigmasterol release. The study employed RAW 264.7 cells to examine the in vitro cytotoxicity and anti-inflammatory effect of stigmasterol/ß-CD-MSNs. For in vivo experimentation, we used healthy control rats and monosodium iodoacetate (MIA)-induced OA rats, separated into five groups, varying the injection substances. In vitro findings indicated that stigmasterol/ß-CD-MSNs suppressed the mRNA expression of key pro-inflammatory mediators such as interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-3 in a dose-dependent manner. In vivo experiments revealed a substantial decrease in the mRNA levels of pro-inflammatory factors in the stigmasterol(50 µg)/ß-CD-MSN group compared to the others. Macroscopic, radiographic, and histological evaluations established that intra-articular injections of stigmasterol/ß-CD-MSNs inhibited cartilage degeneration and subchondral bone deterioration. Therefore, in a chemically induced OA rat model, intra-articular stigmasterol delivery was associated with reduction in both local and systemic inflammatory responses, alongside a slowdown in joint degradation and arthritic progression.

Association between systemic sclerosis and venous thromboembolism, pulmonary embolism, and deep vein thrombosis: a meta-analysis.

OBJECTIVE: This study aimed to analyze the published data pertaining to the correlation between venous thromboembolism (VTE) and systemic sclerosis (SSc). METHODS: We conducted manual searches and explored MEDLINE, EMBASE, and Cochrane databases to review papers reporting the risk of VTE in patients with SSc. A meta-analysis was performed exploring the relative risks (RRs) of deep vein thrombosis (DVT), pulmonary embolism (PE), and VTE in these individuals. RESULTS: Six trials that included 41,105 patients with SSc were eligible for inclusion. A meta-analysis of the six included studies revealed a statistically significant correlation (RR 2.372, 95% confidence interval [CI] = 1.608-3.500, p < 0.001) between the risk of VTE and SSc. Regional subgroup study revealed a strong correlation between SSc and VTE risk in Americans, Europeans, and Asians. Additionally, a significant correlation between SSc and PE risk was observed (RR 3.154, 95% CI = 1.320-7.539, p = 0.010). Finally, the meta-analysis revealed a substantial correlation (RR 5.190, 95% CI = 1.513-17.01, p = 0.009) between the risk of DVT and SSc. CONCLUSION: This meta-analysis showed that SSc is linked to an increased risk of DVT, PE, and VTE. This finding underscores the importance of close monitoring for the emergence of these conditions in patients with SSc.

Comparison of the efficacy and safety of olokizumab at different dosages in patients with active rheumatoid arthritis: a network meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to assess the relative efficacy and safety of olokizumab at different dosages in patients with active rheumatoid arthritis (RA). METHODS: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of olokizumab administered intravenously to RA patients at 64 mg/kg every 2 or 4 weeks (Q2 or Q4W). RESULTS: Five RCTs comprising 2609 patients met the inclusion criteria. Both olokizumab Q2 and Q4W treatments achieved a significant American College of Rheumatology 20% response (ACR20) compared with the placebo (odds ratio [OR] 3.21, 95% credible interval [CrI] 2.53-4.09; OR 3.05, 95% CrI 2.43-3.86). However, olokizumab Q2W was associated with the most favorable surface using the cumulative ranking curve (SUCRA) for the ACR20 response rate. The ranking probability based on the SUCRA indicated that olokizumab Q2W had the highest probability of being considered the best treatment option for achieving the ACR20 response rate, followed by olokizumab Q4W, adalimumab, and placebo. The ACR50 and 70 response rates showed a similar distribution pattern to the ACR20 response rate, except that olokizumab Q4W had a higher-ranking probability than olokizumab Q2W for ACR50. The SUCRA rating likelihood of adverse events (AEs) and withdrawal due to AEs showed that a placebo was likely to be the best intervention. CONCLUSION: Both olokizumab Q2 and Q4W were efficacious and well-tolerated treatments for active RA.

Relative efficacy and safety of calcineurin inhibitor, mycophenolate mofetil, and azathioprine as maintenance therapies for lupus nephritis: a network meta-analysis.

OBJECTIVE: This study aimed to assess the relative efficacy and safety of calcineurin inhibitor (CNI), mycophenolate mofetil (MMF), and azathioprine (AZA) as maintenance therapies for lupus nephritis. METHODS: Randomized controlled trials (RCTs) examining the efficacy and safety of CNI, MMF, and AZA as maintenance therapies in patients with lupus nephritis were included. We performed a Bayesian random-effects network meta-analysis to combine the direct and indirect evidence from RCTs. RESULTS: Ten RCTs comprising 884 patients were included in the study. Although the difference was not statistically significant, MMF showed a trend toward a lower relapse rate compared with AZA (odds ratio [OR] 0.72, 95% credible interval [CrI] 0.45-1.22). Similarly, tacrolimus showed a trend toward a lower relapse rate compared with AZA (OR 0.85, 95% CrI 0.34-2.00). Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that MMF had the highest probability of being the best treatment based on the relapse rate, followed by CNI and AZA. The incidence of leukopenia in the MMF and CNI groups was significantly lower than that in the AZA group (OR 0.12, 95% CrI 0.04-0.34; OR 0.16, 95% CrI 0.04-0.50; respectively). Fewer patients with infections were observed in the MMF group than in the AZA group, although the difference was not statistically significant. The analysis of withdrawals due to adverse events showed a similar pattern. CONCLUSION: Lower relapse rates combined with a more favorable safety profile suggest that CNI and MMF are superior to AZA as maintenance treatments in lupus nephritis patients.

Role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential biomarkers in Behçet's disease: a meta-analysis.

AIM: The mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have attracted interest as possible indicators of inflammation and disease activity in various diseases. This meta-analysis assessed the association between NLR, MPV, PLR, and Behçet's disease (BD) and their correlation with disease activity and thrombosis. METHODS: A thorough search of the Medline, Embase, and Cochrane databases was performed to identify relevant studies. Studies comparing NLR, MPV, and PLR between patients with BD and healthy controls, as well as studies examining these measures in connection with disease activity and thrombosis in BD satisfied the inclusion criteria. The standardized mean difference (SMD) and 95% confidence interval (CI) were used to calculate the effect sizes. RESULTS: This meta-analysis included 24 articles. The findings revealed no discernible differences in MPV between the BD and control groups (p = 0.992). NLR was substantially higher in the BD group than in the control group (p < 0.001). PLR was higher in the BD group than in the control group (p = 0.030), indicating that BD is associated with a larger PLR. Patients with active and inactive BD did not vary significantly in terms of disease activity according to the MPV. Comparing MPV between patients with BD with and without thrombosis showed no discernible changes. However, individuals with active BD had a considerably higher NLR and PLR than those with inactive BD (p = 0.003 and p = 0.005, respectively). The statistical significance threshold for the association between NLR, PLR, and thrombosis in patients with BD was not met. CONCLUSION: NLR and PLR can be regarded as general markers of inflammation according to the results of this meta-analysis.

Standardized mortality ratios in systemic sclerosis: a meta-analysis assessing overall and sex- and disease subtype-specific differences.

OBJECTIVE: This study aims to evaluate the overall and sex- and illness subtype-specific standardized mortality ratios (SMRs) in patients with systemic sclerosis (SSc). METHODS: We searched and examined studies that compared the overall and sex- and illness subtype-specific SMRs in patients with SSc to those in the general population using MEDLINE, EMBASE, and Cochrane databases (until May 2023). We then conducted a meta-analysis of the overall and sex- and illness subtype-specific SMRs in patients with SSc. RESULTS: Overall, 29 studies including 30,673 patients with SSc and 5582 deaths met the inclusion criteria. Patients with SSc had a higher overall SMR than that in the general population (SMR: 2.742, 95% confidence interval [CI]: 2.224-3.38091, p < 0.001). The SMR significantly increased in populations from Europe, North America, Asia, and Oceania according to regional stratification. A sex-specific meta-analysis revealed a substantial increase in the SMR in both men and women (SMR: 3.598, 95% CI: 3.097-4.180, p < 0.001; SMR: 2.833, 95% CI: 2.4384-3.292, p < 0.001, respectively) and the mortality rate was higher in men compared to women. A substantial increase in the SMR in diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc) was observed in a disease subtype-specific meta-analysis. In addition, the SMR in the dcSSc group was higher than that in the lcSSc group (SMR: 4.726, 95% CI: 3.795-5.885, p < 0.001; SMR: 1.987, 95% CI: 1.586-2.489, p < 0.001, respectively). CONCLUSION: Our findings demonstrated that the mortality rate in patients with SSc was 2.74-times greater than that in the general population. The mortality rate was higher in men compared to women. Additionally, compared to patients with lcSSc, those with dcSSc showed much higher fatality rates.

A meta-analysis of the association between the ATIC 347 C/G polymorphism and methotrexate responsiveness and toxicity in rheumatoid arthritis.

OBJECTIVES: The purpose of this study was to determine whether the 347 C/G polymorphism in the 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC) gene predicts the responsiveness to or toxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHOD: To identify relevant publications, we searched the Medline, Embase, Cochrane, and Web of Science databases. We performed a meta-analysis of studies on the relationship between the ATIC 347 C/G polymorphism and MTX toxicity or non-responsiveness in patients with RA. RESULTS: Thirteen studies consisting of 3,185 patients with RA satisfied our inclusion criteria. The analysis included 10 studies on MTX responsiveness and seven studies on MTX toxicity in patients with RA in connection with ATIC 347C/G polymorphism. According to our meta-analysis, the ATIC 347 GG genotype and failure to respond to MTX treatment were significantly associated (OR = 0.741, 95% CI = 0.591-0.929, p=0.009). According to stratification by ethnicity, this genotype was significantly associated with non-responsiveness to MTX in Europeans (OR=0.548, 95% CI=0.377-0.796, p=0.002) but not in Asian populations (OR=0.882, 95% CI=0.665-1.1172, p=0.388). However, analyses employing allelic, dominant, and homozygous contrast models failed to detect any relationship between the polymorphism and the failure to respond to MXT. However, the ATIC 347GG genotype and MTX toxicity were not associated (OR=1.278, 95% CI=0.937-1.745, p=0.121). Asian and European populations showed no evidence of a relationship between the ATIC 347GG genotype and MTX toxicity (OR=1.252, 95% CI=0.905-1.732, p=0.175 and OR =1.617, 95% CI=0.549-4.765, p=0.383, respectively). CONCLUSIONS: This meta-analysis revealed that ATIC 347 C/G polymorphism was related to non-responsiveness to MTX in European populations with RA. However, no significant correlation was found with MTX toxicity.

Efficacy and Safety of Nintedanib in Patients with Interstitial Lung Disease with or without Systemic Sclerosis: A Meta-Analysis.

Background: Nintedanib is a potent intracellular inhibitor of tyrosine kinases and modulates the pathways involved in the development of fibrosis. We assessed nintedanib efficacy and safety in interstitial lung disease (ILD) patients. Methods: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register to identify available articles (up to April 2022). We conducted a meta-analysis of randomized controlled trials (RCTs) examining nintedanib efficacy and safety in patients with ILD with or without systemic sclerosis (SSc). Results: Meta-analysis of five RCTs including 2,470 patients with ILD (1,343 nintedanib group and 1,127 controls) revealed that the annual rate of change in forced vital capacity (FVC) was significantly lower in the ILD group than in the control group (standardized mean difference [SMD] = 0.336; 95% confidence interval (CI) = 0.256-0.416, P<0.001). Stratification by disease type showed a low annual rate of change in FVC in patients with and without SSc (SMD = 0.389, 95% CI=0.294-0.478, P<0.001; SMD=0.177, 95% CI=0.013-0.340, P<0.00). The incidence of serious adverse events did not differ between the nintedanib and placebo groups; however, adverse events (AEs) and withdrawals due to AEs were significantly higher in the nintedanib group than in the placebo group (SMD =2.365, 95% CI=1.673-3.343, P<0.001; SMD =1.740, 95% CI= 1.385-2.185, P<0.001). Conclusion: Nintedanib is effective for ILD with or without SSc. However, it increased the incidence of AEs and withdrawals due to AEs.

Treatment of active systemic lupus erythematosus with baricitinib: A meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to evaluate the safety and effectiveness of baricitinib in patients with systemic lupus erythematosus (SLE). METHODS: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Register to find relevant publications. Using data from randomized controlled trials (RCTs), we performed a meta-analysis to investigate the safety and efficacy of baricitinib in patients with active SLE who did not respond well to standard treatments. RESULTS: A total of 1849 individuals (1235 experimental participants and 614 controls) from three RCTs on baricitinib were included. A reduction of ≥ 4 points from baseline in SLEDAI-2K score in the baricitinib 4 mg group was greater than the placebo group's reduction (odds ratio [OR] = 1.407, 95% confidence interval [CI] 1.123-1.763, p = .003). The baricitinib 4 mg group significantly outperformed the placebo group in terms of SLEDAI-2K remission of arthritis or rash (OR = 1.327, 95% CI = 1.059-1.663, p = .014). Other effectiveness outcomes such as the SRI4 response did not substantially improve in the baricitinib 4 mg group when compared with the placebo group. And there were no significant increase in the efficacy outcomes in the baricitinib 2 mg group than in the placebo group. However, there was a substantially higher incidence of severe adverse events (SAE) and serious infections in the baricitinib 4 mg group (OR = 1.493, 95% CI = 1.002-2.225, p = .049; OR = 2.303, 95% CI = 1.147-4.622, p = .019) compared to the placebo group. There were no differences between the baricitinib 2 mg and placebo groups in any of the safety outcome data. CONCLUSION: Meta-analysis reveals that baricitinib 4 mg is beneficial for treating active SLE in terms of a reduction of ≥ 4 points from baseline in SLEDAI-2K score and SLEDAI-2K remission of arthritis or rash. However, the higher frequency of SAEs and serious infections was observed in the group receiving baricitinib 4 mg.

The role of NLRP3 and CARD8 polymorphisms in the risk of rheumatoid arthritis: A meta-analysis of genetic association studies.

OBJECTIVE: To investigate the potential associations between rheumatoid arthritis (RA) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) rs35829419, rs10754558, s4612666, and caspase recruitment domain family member 8 (CARD8) rs2043211 polymorphisms. METHODS: Relevant papers were searched for in MEDLINE, Embase, and Web of Science. Allele contrast, recessive, dominant, and homozygote contrast models were used to investigate the relationship between the NLRP3 rs35829419, rs10754558, and s4612666, and CARD8 rs2043211 polymorphisms and RA. This review was registered with PROSPERO (CRD42023451231). RESULTS: The meta-analysis included 11 comparative studies comprising 3789 patients with RA and 3956 controls. No significant association was found between NLRP3 rs35829419 C allele and RA in Europeans, Arabs, or Latinos. The NLRP3 rs10754558 G allele was not associated with RA in the Asian or Arab populations. However, a single study in Latin America discovered a link between RA and the NLRP3 rs10754558 G allele. The NLRP3 rs4612666 T allele was not associated with RA, according to the meta-analysis. When ethnicity was stratified, there was no association between the NLRP3 rs4612666 T allele and RA, except for a single study that found an association among Arabs. The CARD8 rs2043211 T allele did not seem to be associated with RA. According to an ethnic stratification study, the CARD8 rs2043211 T allele did not appear to be associated with RA in Europeans, Arabs, or Latinos. CONCLUSIONS: The meta-analysis indicated that the NLRP3 rs35829419, rs10754558, and s4612666 polymorphisms, as well as the CARD8 rs2043211 polymorphism, were not linked to RA susceptibility.

Associations Between Osteopontin Variants and Systemic Lupus Erythematosus: A Meta-Analysis.

Objective: Osteopontin (OPN) increases T-cell proliferation, interferon production, and CD40 ligand expression, which leads to B-cell proliferation and antibody production. This study was designed to determine whether OPN variants are associated with susceptibility to systemic lupus erythematosus [SLE]. Methods: We searched the Medline, Embase, and KoreaMed databases for available articles. We performed a meta-analysis on the association of OPN 707 T/C (rs1126616) at exon 6, 1083 G/A (rs112772) at the 3'-untranslated region (3'-UTR), 1239 C/A (rs9138) at 3'-UTR, and 9250 T/C (rs11229919) variants in exon 7 with susceptibility to SLE. Results: Ten studies from 9 articles with 2175 SLE patients and 3233 controls were included. The meta-analysis showed a significant association between SLE and the 707 T allele of the OPN 707 T/C variant (odds ratio [OR] = 1.522, 95% confidence interval [CI] = 1.101-2.105, p = 0.044). Stratification by ethnicity indicated an association between the OPN 707 T/C variant and SLE in European and Arab populations. The meta-analysis also revealed a significant association between the OPN 9250 C allele and SLE in the Asian and Arab populations. A significant association was also identified between the +1239 C allele of the OPN 1239 C/A variant and SLE (OR = 1.192, 95% CI = 1.008-1.410, p = 0.040). The meta-analysis indicated no allelic association between SLE and OPN 1083 G/A and the OPN 1239 C/A variants. Conclusions: The OPN 707 T/C variant is associated with SLE susceptibility in European and Arab populations and the OPN 9250 T/C variant is associated with SLE susceptibility in Asian and Arab populations. In addition, associations were found between the OPN 1239 C/A variant and SLE.

Relative Remission and Low Disease Activity Rates of Tofacitinib, Baricitinib, Upadacitinib, and Filgotinib versus Methotrexate in Patients with Disease-Modifying Antirheumatic Drug-Naive Rheumatoid Arthritis.

BACKGROUND: The relative efficacy of Janus kinase (JAK) inhibitors in producing remission and low disease activity (LDA) states remains unknown since there are currently no trials that provide direct comparisons among JAK inhibitors in disease-modifying antirheumatic drug (DMARD)-naive patients with rheumatoid arthritis (RA). OBJECTIVES: This study aimed to assess the relative remission and LDA rates of tofacitinib, baricitinib, upadacitinib, and filgotinib compared to those of methotrexate (MTX) in DMARD-naive patients with RA. METHOD: We conducted Bayesian network meta-analysis and included information from direct and indirect comparisons from randomized controlled trials that examined remission (Disease Activity Score in 28 Joints using C-reactive protein level [DAS28-CRP] <2.6) and LDA (DAS28-CRP ≤ 3.2) produced by tofacitinib, baricitinib, upadacitinib, filgotinib monotherapy, and MTX in patients with DMARD-naive RA. RESULTS: Four randomized controlled trials, comprising 2,185 patients, met the inclusion criteria. This network meta-analysis showed that treatment with tofacitinib, baricitinib, upadacitinib, and filgotinib achieved a significantly higher remission rate than that with MTX (odds ratio [OR] = 4.13, 95% CI = 2.88-6.02; OR = 2.12, 95% CI = 1.17-4.13; OR = 1.95, 95% CI = 1.10-3.50; OR = 1.79, 95% CI = 1.27-3.53). The ranking probability based on the surface under the cumulative ranking curve indicated that upadacitinib 15 mg had the highest probability of achieving remission (SUCRA = 0.985), followed by tofacitinib 5 mg (SUCRA = 0.574), baricitinib 4 mg (SUCRA = 0.506), filgotinib 200 mg (SUCRA = 0.431), and MTX (SUCRA = 0.004). Moreover, treatment with tofacitinib, baricitinib, upadacitinib, and filgotinib achieved significantly higher LDA rate than that with MTX. The ranking probability for LDA was similar to that for remission; upadacitinib 15 mg had the highest probability of achieving LDA, followed by tofacitinib 5 mg, baricitinib 4 mg, filgotinib 200 mg, and MTX. CONCLUSIONS: Upadacitinib seems to be one of most effective interventions for achieving remission and LDA in DMARD-naive patients with RA based on the comparative analysis, and there are differences in remission and LDA rates induced by different JAK inhibitors.

Associations between circulating interleukin-17 levels and Behcet's disease and between IL-17 gene polymorphisms and disease susceptibility: a meta-analysis.

OBJECTIVES: To systematically investigate the relationship between circulating interleukin-17 (IL-17) levels and Behçet's disease (BD) and the associations between polymorphisms in IL17 genes and BD susceptibility. METHODS: We searched the Medline, Embase, and Cochrane databases for relevant articles. We performed a meta-analysis of serum/plasma IL-17 levels in BD patients and controls and evaluated the associations between IL17A rs4711998, rs8193036, and rs2275913 and IL17F rs763780 and rs2397084 polymorphisms and the risk of BD. RESULTS: Twelve studies, involving 901 patients with BD and 1,131 controls, were included. Our meta-analysis revealed that circulating IL-17 levels were significantly higher in the BD group than in the control group (SMD = 1.422, 95% confidence interval [CI] = 0.689-2.155, p<0.001). Subgroup analysis by data type indicated higher IL-17 levels in the BD group in both the original and calculated data populations. Stratification by publication year revealed significantly lower vitamin D levels in the SSc group in both recent and older publication years. No significant differences in IL-17 levels were observed between the active and inactive disease groups. We found no evidence of associations between BD and IL17A rs2275913, L17F rs763780, or rs2397084 polymorphisms. However, a significant association was found between BD and IL17A rs4711998 and rs8193036 polymorphisms in the pooled cohort of affected individuals compared to that in pooled controls (odds ratio [OR] = 1.347, 95% CI = 1.043-1.741, p<0.001; OR = 0.691, 95% CI = 0.542-0.880, p=0.003). CONCLUSIONS: This meta-analysis revealed significantly higher circulating IL-17 levels in BD patients and showed evidence of associations between IL17A rs4711998 and rs8193036 polymorphisms and BD.

Associations between blood IL-33 levels and IL-33 gene polymorphisms with susceptibility to systemic lupus erythematosus: A meta-analysis.

OBJECTIVES: This study investigated the relationship between circulating interleukin-33 (IL-33) levels and systemic lupus erythematosus (SLE) along with polymorphisms in the IL-33 gene and SLE susceptibility. METHOD: The MEDLINE, EMBASE, and Cochrane Library databases (to May 2023) were searched for relevant publications. Using a meta-analysis we investigated serum/plasma IL-33 levels in patients with SLE and controls, and the relationship between IL-33 rs1929992, rs1891385, rs7044343, rs1095498, and rs10975579 polymorphisms and the risk of developing SLE. RESULTS: Nine studies focusing on 1,935 patients with SLE were included. IL-33 levels were significantly higher in the SLE group than in the control group (SMD = 2.140, 95% CI = 1.068-3.212, p < .001). Asian, European, and Arab groups have shown increased IL-33 levels in SLE populations, according to ethnic stratification. Regardless of the sample size, variable adjustment, data format, or publication year, the subgroup analysis showed significantly higher IL-33 levels in the SLE group. This meta-analysis supported the significance of the link between SLE and the IL-33 rs1891385 C allele (OR, 1.525; 95% CI, 11.310-1.777; p = .010). A similar association was found between the IL-33 rs1891385 C/A polymorphism and SLE, using homozygote comparisons and dominant and recessive models. However, this meta-analysis found no association between the IL-33 polymorphisms rs1929992, rs7044343, rs1095498, and rs10975579 and susceptibility to SLE. CONCLUSIONS: This meta-analysis identified significantly higher levels of circulating IL-33 in patients with SLE as well as an association between IL-33 rs1891385 and SLE.

Circulating leptin and its correlation with rheumatoid arthritis activity: a meta-analysis.

Objective: The aim of the study was to investigate the association between the levels of leptin in the circulating of individuals with rheumatoid arthritis (RA) and the severity of the disease. Methods: We looked through the databases of Embase, Medline, and the Cochrane Library. We conducted a meta-analysis on the correlations between circulating leptin and the Disease Activity Score 28-erythrocyte sedimentation rate (DAS28-ESR) and C-reactive protein (CRP) levels in RA patients, as well as a meta-analysis of circulating or circulating leptin levels in RA patients. Results: This meta-analysis study analyzed 42 different comparisons from 37 different publications, including a total of 2,350 patients with RA and 1,815 controls. The RA group had substantially higher leptin levels than the control group (standardized mean difference [SMD]=0.507, 95% confidence interval [CI]=0.309~0.704, p<0.001). The finding that RA patients had higher leptin levels was unaffected by sample size. The correlation between circulating leptin levels and DAS28 is statistically significant (correlation coefficient=0.247, 95% CI=0.087~0.396, p=0.003). Leptin levels are also correlated with CRP levels (correlation coefficient=0.203, 95% CI=0.048~0.349, p=0.010). Conclusion: This comprehensive meta-analysis demonstrates that the circulating leptin levels of RA patients are elevated, and provides compelling evidence of the significant relationship between leptin levels and the activity of RA. The findings of this research suggest that leptin plays a significant role in the pathophysiology of this disease.

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

OBJECTIVE: This study aimed to examine whether polymorphisms in toll-like receptor 9 (TLR9) contribute to vulnerability to systemic lupus erythematosus (SLE). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Characterization of virus-mediated autoimmunity and the consequences for pathological process in patients with systemic lupus erythematosus.

INTRODUCTION/OBJECTIVES: This study aimed to identify differentially expressed genes (DEGs) of systemic lupus erythematosus (SLE) using gene expression-based computational methodologies to analyze disease-immune interactions, which affect the development and progression of SLE. METHOD: Twenty-six patients with SLE and 46 healthy controls were selected from the Gene Expression Omnibus (GEO) database. The significantly enriched immune and virus-related gene lists were computed and visualized by using the DEGs from the gene set enrichment analysis (GSEA). Quantification of 38 immune cells was performed in determining the impact of immune cells on the virus mediated immunity in SLE by using ImmQuant algorithm. RESULTS: Thirty-nine upregulated and 57 downregulated were identified in SLE patient compared to the healthy controls. Upregulated genes were significantly implicated in Gene Ontology gene sets as cytokine mediated signaling, secretion, and exocytosis in immune response pathways in 26 female SLE patients. In addition, these genes were enriched in hepatitis C, influenza A, measles, Epstein-Barr virus, and herpes simplex virus 1 infection in Kyoto Encyclopedia of Genes and Genomes pathways. Especially, FCGR1A, IRF7, OAS2, CAMP, MX1, OAS3, OAS1, DEFA3, ISG15, and RSAD2 were involved in virus mediated SLE mechanism, and the expression for OAS1, OAS2, and IRF7 was closely associated with the quantities of colony forming unit-monocyte and colony forming unit-granulocyte. CONCLUSIONS: Identifying virus-mediated SLE genes and quantifies of immune cells were used to understand the pathological process and perform early diagnosis of female SLE, and will lead to clinical tools for treating SLE in patients. Key Points • Using gene expression-based computational methodologies, the 57 immune and viral genes were significantly upregulated in 26 SLE patients. • The identified three key  viral genes such as OAS1, OAS2, and IF7 were closely associated with colony-forming unit-monocytes and colony-forming unit-granulocytes, which affect the virus mediated immunity in SLE. • The viral genes and quantifies of immune cells are useful in understanding pathogenesis of SLE, and this will provide clinical strategies of potential treatment choices in SLE patients.

Association between functional FCGR3A F158V and FCGR2A R131H polymorphisms and responsiveness to rituximab in patients with autoimmune diseases: a meta-analysis.

OBJECTIVES: To investigate the association between the functional Fc gamma receptor 3 A (FCGR3A) V158F and FCGR2A R131H polymorphisms and rituximab therapy in patients with autoimmune diseases. METHODS: We searched the Medline, Embase, and Cochrane databases for relevant articles. We conducted a meta-analysis of the association between FCGR3A V158F and FCGR2A R131H polymorphisms and responsiveness to rituximab in patients with autoimmune diseases. RESULTS: Eleven studies, consisting of 661 responders and 267 non-responders for FCGR3A V158F polymorphism and 156 responders and 89 non-responders for FCGR2A R131H polymorphism, were included. The meta-analysis revealed a significant association between the FCGR3A V allele and responsiveness to rituximab (odds ratio [OR] = 1.600, 95% confidence interval [CI] = 1.268-2.018, P < 0.001). Furthermore, associations were found using the dominant and homozygous contrast models. Subgroup analysis showed an association between the FCGR3A V allele and responsiveness to rituximab in European, RA, ITP, small (<50) and large (≥50) groups, and short- (≤6 months) and long-term follow-up periods (≥6 months). These associations were also found in recessive, dominant or homozygous contrast models. Meta-analysis revealed no association between the FCGR2A R allele and responsiveness to rituximab (OR = 1.243, 95% CI = 0.825-1.873, P = 0.229). CONCLUSIONS: We demonstrated that the FCGR3A F158V polymorphism is associated with better responsiveness to rituximab therapy in patients with autoimmune diseases, indicating that individuals carrying the FCGR3A V allele will likely respond better to rituximab. However, FCGR2A R131H polymorphism was not associated with better response to rituximab.

Efficacy of initiating urate-lowering therapy during an acute gout episode: a meta-analysis.

OBJECTIVE: This study aimed to evaluate the effectiveness of initiating urate-lowering therapy (ULT) during acute gout episodes. METHODS: We performed a literature search using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (from inception to February 2023). We conducted a comprehensive review and meta-analysis of randomized controlled trials (RCTs) that examined the efficacy of ULT in individuals with acute gout flares. RESULTS: This review included six RCTs with 479 patients (225 experimental participants and 254 controls). The experimental group had longer days to resolution than did the control group. There was no significant difference in the pain visual analogue scale score between the groups by day 10. Erythrocyte sedimentation rate and C­reactive protein level did not significantly differ between the groups by days 7 to 14. Both groups had similar rates of recurrent gout attacks by 30 days. There was no significant between-group difference in the dropout rate. CONCLUSION: Initiating ULT therapy during a gout attack does not appear to increase the duration of the flare or aggravate pain. Despite these findings, further studies with larger sample sizes are necessary to support these conclusions.