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Objective: The aim of this study is to determine whether the functional interferon regulatory factor 5 (IRF5) polymorphism rs2004640 is associated with susceptibility to systemic lupus erythematosus (SLE) in multiple ethnic populations. Methods: A meta-analysis was conducted on the T allele of the IRF5 rs2004640 polymorphism in all study participants as well as each ethnic population. Results: Twenty research articles that included 28 comparative studies of 20,892 patients and 24,930 controls were included in the meta-analysis. The Asian population had a much lower prevalence of the T allele than any other study population at 28%, and the European population had the highest prevalence of the T allele at 52%. Meta-analysis showed an association between the IRF5 rs2004640 polymorphism and SLE in all participants (odds ratio = 1.472, 95% confidence interval = 1.370–1.582, p < 0.001). Analysis after stratification by ethnicity indicated that the IRF5 rs2004640 T allele is significantly associated with SLE in Europeans, Asians, Latin Americans and Arabs. Conclusions: This meta-analysis confirms that the IRF5 rs2004640 polymorphism is associated with SLE susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the relationship between circulating prolactin level and systemic lupus erythematosus (SLE), and to establish a correlation between plasma/serum prolactin levels and SLE activity. Methods: We performed a meta-analysis comparing the plasma/serum prolactin levels in patients with SLE to controls, and examined correlation coefficients between circulating prolactin level and SLE disease activity. Results: Twentyfive studies with a total of 1056 SLE patients and 426 controls were included. Prolactin levels were significantly higher overall in the SLE group than in the control group (standardized mean difference (SMD) = 0.987, 95% CI = 0.512-1.463, p = 4.7 x 10-5). Stratification by ethnicity showed significantly elevated prolactin levels in the SLE group in Asian, Latin American, and mixed populations (SMD = 0.813, 95% CI = 0.137-1.490, p = 0.018; SMD = 0.981, 95% CI = 0.307-1.655, p = 0.004; SMD = 1.469, 95% CI = 0.443-2.495, p = 0.005, respectively), but not in the European population. Subgroup analysis by sample size showed significantly higher prolactin levels in the SLE group by small (n < 30) and large sample numbers (n > 30). Meta-analysis of correlation coefficients showed a significantly positive correlation between circulating prolactin level and SLE activity (correlation coefficient = 0.379, 95% CI = 0.026-0.487, p = 4.0 x 10-9). Circulating prolactin levels were positively associated with SLE activity in European, Asian, and mixed populations (SMD = 0.532, 95% CI = 0.443-0.609p < 1.0 x 10-8; SMD = 0.427, 95% CI = 0.240-0.583, p = 2.4 x 10-5; SMD = 0.433, 95% CI = 0.212-0.591, p = 2.7 x 10-5, respectively). Conclusions: Our meta-analysis demonstrated that circulating prolactin levels are higher in patients with SLE, and that a significantly positive correlation exists between prolactin levels and SLE activity. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the relationship between telomere length and systemic lupus erythematosus (SLE). Methods: PUBMED and EMBASE databases were searched; metaanalyses were performed comparing telomere length in SLE patients and healthy controls, and on SLE patients in subgroups based on ethnicity, sample type, assay method and data type. Results: Eight studies including 472 SLE patients and 365 controls were ultimately selected which showed that telomere length was significantly shorter in the SLE group than in the control group (standardized mean difference (SMD)=-0.835, 95% confidence interval (CI)=-1.291 to -0.380, p=3.3×10-4). Stratification by ethnicity showed significantly shortened telomere length in the SLE group in Caucasian, Asian and mixed populations (SMD=-0.455, 95% CI=-0.763 to -0.147, p=0.004; SMD=-0.887, 95% CI=-1.261 to -0.513, p=3.4×10-4; SMD=-0.535, 95% CI=-0.923 to -0.147, p=0.007; respectively). Furthermore, telomere length was significantly shorter in the SLE group than in the control group in whole blood and peripheral blood mononuclear cell groups (SMD=-0.361, 95% CI=-0.553 to -0.169, p=2.3×10-4; SMD=-1.546, 95% CI=-2.583 to -0.510, p=0.003; respectively); a similar trend was observed in leukocyte groups (SMD=-0.699, 95% CI=-1.511 to -0.114, p=0.092). Meta-analyses based on assay method or data type revealed similar associations. Conclusions: Our meta-analysis demonstrated that telomere length was significantly shorter in patients with SLE, regardless of ethnicity, sample type or assay method evaluated. [ABSTRACT FROM AUTHOR]

Objective This study aimed to systemically review the evidence regarding the relationship between circulating blood osteopontin (OPN) level and systemic lupus erythematosus (SLE), correlation between serum OPN levels and SLE activity, and association between OPN polymorphisms and SLE susceptibility. Methods We conducted a meta-analysis on the serum/plasma OPN levels in SLE patients and healthy controls, correlation coefficients between the circulating OPN level and SLE Disease Activity Index (SLEDAI) in SLE patients, and the association between OPN polymorphisms and SLE risk. Results Nine studies with 1938 SLE patients and 3037 controls were included. Meta-analysis revealed that, compared with the control group, the OPN level was significantly higher in the SLE group (SMD = 0.965, 95% CI = 0.337–1.393, p = 0.001) and in the SLE group with renal disease (SMD = 2.219, 95% CI = 0.681–3.757, p = 0.005). Meta-analysis of correlation coefficients showed a trend of positive correlation between the circulating OPN level and SLEDAI (correlation coefficient = 0.590, 95% CI = −0.025 to 0.881, p = 0.059). While no association was found between SLE and the OPN 707 T/C and 1083 G/A polymorphisms, a significant association was identified between the OPN 1239 C allele and SLE (OR = 1.192, 95% CI = 1.008–1.410, p = 0.040), and between the OPN 9250 C allele and SLE in Asians (OR = 2.070, 95% CI = 1.570–2.730, p = 2.5 × 10−7). Conclusions Our meta-analysis revealed a significantly higher circulating OPN level in SLE patients, a trend of positive correlation between OPN levels and SLE activity, and a significant association between OPN 1239 C/A and 9250 C/T polymorphisms, and SLE development. [ABSTRACT FROM AUTHOR]

Objective This study determined whether NLRP3 polymorphisms rs35829419 C/A and rs10754558 C/G were associated with autoimmune and inflammatory diseases. Methods An association between the NLRP3 rs35829419 C/A and rs10754558 C/G polymorphisms and autoimmune and inflammatory diseases was determined by performing a meta-analysis by using (1) allele contrast, (2) recessive, (3) dominant, and (4) co-dominant models. Results Thirty comparative studies involving 8069 patients and 8824 controls were included in the meta-analysis. No association was observed between autoimmune and inflammatory diseases and NLRP3 rs35829419 C allele (OR = 1.020, 95% CI = 0.804–1.295, p = 0.869). Stratification by ethnicity showed no association between the NLRP3 rs35829419 C allele and autoimmune and inflammatory diseases in European, Latin American, and Polynesian populations. Stratification by disease type showed no association between the NLRP3 rs35829419 C allele and gout, SLE, RA, celiac disease, and Crohn’s disease. Moreover, no association was observed between autoimmune and inflammatory diseases and the NLRP3 rs10754558 C allele (OR = 1.057, 95% CI = 0.950–1.177, p = 0.310). However, stratification by ethnicity showed an association between the NLRP3 rs10754558 C allele and autoimmune and inflammatory diseases in the Latin American (OR = 1.399, 95% CI = 1.201–1.630, p = 1.6 × 10–6) but not in European and Asian populations. Further, stratification by disease type showed a significant association of the NLRP3 rs10754558 C allele with SLE (OR = 1.465 95% CI = 1.144–1.875, p = 0.002) but not with gout and celiac disease. The same pattern was observed for the NLRP3 rs10754558 C allele in the recessive model. Conclusions Our results indicated that the NLRP3 rs10754558 C/G polymorphism was associated with susceptibility to SLE and with autoimmune and inflammatory diseases in Latin American individuals. [ABSTRACT FROM AUTHOR]

Objective This study aimed to explore whether TYK2 polymorphisms are associated with susceptibility to autoimmune rheumatic diseases. Methods We conducted a meta-analysis on the association between TYK2 polymorphisms and autoimmune rheumatic diseases. Results Twelve studies with a total of 16,335 patients and 30,065 controls were included in the meta-analysis. Meta-analysis revealed an association between rheumatic diseases and the 2 allele of the TYK2 rs2304256 (OR = 0.885, 95% CI = 0.802–0.978, p = 0.016). Furthermore, stratification by ethnicity identified a significant association between this polymorphism and rheumatic diseases in Caucasians (OR = 0.822, 95% CI = 0.706–0.889, p = 9.5 × 10−7), but not in Asians (OR = 1.127, 95% CI = 0.835–1.522, p = 0.434). Meta-analysis by rheumatic disease type revealed a significant association between the 2 allele of the TYK2 rs2304256 and SLE in Caucasians (OR = 0.737, 95% CI = 0.673–0.808, p < 1.0 × 10−8) but not in Asians (OR = 1.211, 95% CI = 0.813–1.804, p = 0.347). Meta-analysis revealed that the rs12720356 polymorphism was associated with susceptibility to rheumatic diseases in Caucasians (OR = 0.812, 95% CI = 0.661–0.997, p = 0.046) but not in Asians. Interestingly, the rs280519 polymorphism was significantly associated with susceptibility to SLE both in Caucasians and Asians. However, no associations were found between the rs12720270, rs280500, rs280523 and rs8108236 polymorphisms and susceptibility to rheumatic diseases. Conclusions This meta-analysis demonstrates that the TYK2 rs2304256 and rs12720356 polymorphisms are associated with susceptibility to rheumatic diseases, rs2304256 polymorphism is associated with SLE in Caucasians, and rs280519 polymorphism is associated with SLE in Caucasians and Asians. [ABSTRACT FROM AUTHOR]

Aims This study aimed to assess all-cause and cause-specific standardized mortality ratios (SMRs) in patients with systemic lupus erythematosus (SLE). Methods We surveyed studies examining all-cause and/or cause-specific SMR in patients with SLE compared to the general population using PUBMED, EMBASE and Cochrane databases and manual searches. We performed a meta-analysis of all-cause, sex-specific, ethnicity-specific, and cause-specific SMRs in SLE patients. Results Fifteen reports including 26,101 patients with SLE with 4640 deaths met the inclusion criteria. Compared to the general population, all-cause SMR was significantly increased 2.6-fold in patients with SLE (SMR 2.663, 95% CI 2.090–3.393, p < 1.0 × 10−8). Stratification by ethnicity showed that all-cause SMR was 2.721 (95% CI 1.867–3.966, p = 1.9 × 10−6) in Caucasians and 2.587 (95% CI 1.475–4.535, p = 0.001) in Asians. Sex-specific meta-analysis revealed that all-cause SMR was 3.141 (95% CI 2.351–4.198, p < 1.0 × 10−8) for women and 3.516 (95% CI 2.928–4.221, p < 1.0 × 10−8) for men. The risk of mortality was significantly increased for mortality due to renal disease (SMR 4.689, 95% CI 2.357–9.330, p = 1.10 × 10−5), cardiovascular disease (CVD) (SMR 2.253, 95% CI 1.304–3.892, p = 0.004), and infection (SMR 4.980, 95% CI 3.876–6.398, p < 1.0 × 10−8), although there was no significant increase in SMR for mortality due to cancer (SMR 1.163, 95% CI 0.572–2.363, p = 0.676). Conclusions Patients with SLE had higher rates of death from all causes, regardless of sex, ethnicity, renal disease, CVD or infection. However, the risk of death due to malignancy was not increased. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to explore whether the interferon (IFN)-γ +874 T/A polymorphism plays a role in modifying the risk of autoimmune diseases. Methods A meta-analysis was conducted on the association between the IFN-γ +874 T/A polymorphism and autoimmune diseases. Results Eighteen studies with a total of 2952 patients and 3832 controls were included in the meta-analysis. The meta-analysis revealed no association between autoimmune diseases and the IFN-γ +874 T allele in all study subjects (odds ratio (OR)=1.023, 95% confidence interval (CI) = 0.894–1.171, p = 0.738), but stratification by ethnicity indicated an association between the IFN-γ +874 T allele and autoimmune diseases in Latin American subjects (OR = 0.780, 95% CI = 0.629–0.953, p = 0.015). Meta-analysis also revealed an association between autoimmune diseases and the IFN-γ +874 T/A polymorphism in Caucasian and Middle Eastern subjects under a dominant inheritance model (OR = 0.686, 95% CI = 0.489–0.964, p = 0.003; OR = 1.414, 95% CI = 1.102–1.813, p = 0.006). Meta-analysis by autoimmune disease type indicated an association between ITP and the IFN-γ +874 T allele (OR = 1.753, 95% CI = 1.228–2.503, p = 0.002), but not for vasculitis, vitiligo, and auto-immune thyroid disease. Meta-analysis also showed a significant association between the IFN-γ +874 T/A polymorphism and systemic lupus erythematosus (SLE) under the dominant model (OR = 1.668, 95% CI = 1.114–2.497, p = 0.013). Conclusions This meta-analysis indicates that the IFN-γ +874 T/A polymorphism may play a significant role in modifying the risk of autoimmune diseases in Caucasian, Latin American, and Middle Eastern subjects, and in particular shows that the IFN-γ +874 T/A polymorphism is associated with increased genetic susceptibility to idiopathic thrombocytopenic purpura and SLE. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to determine whether polymorphisms of the Toll-like receptor (TLR) genes are associated with susceptibility to systemic lupus erythematosus (SLE). Methods The authors conducted a meta-analysis of the relationship between 12 TLR polymorphisms and SLE susceptibility. Results In total, 26 studies that involved 11,984 patients and 14,572 controls were included in the meta-analysis. The meta-analysis showed no association between the two alleles of the rs352140, rs5743836, and rs352139 polymorphisms of TLR9 and SLE, but indicated an association between the two alleles of the rs187084 polymorphism (TLR9) and SLE in the overall population (OR = 0.869, 95% CI = 0.762–0.992, P = 0.038). No association was detected between rs3764880 (TLR8) and SLE; however, our meta-analysis indicated an association between rs3764879 (TLR8) and SLE in Caucasians (OR = 1.414, 95% CI = 1.139–1.756, P = 0.002). An association between rs179008 (TLR7) and SLE was found in the African (OR = 0.430, 95% CI = 0.238–0.775, P = 0.005), but not in the Caucasian population (OR = 1.206, 95% CI = 0.932–1.614, P = 0.145). Furthermore, our meta-analysis indicated a significant association between rs3853839 (TLR7) and SLE in the Asian population (OR = 0.773, 95% CI = 0.735, 0.823, P < 1.0 × 10−9). No associations were found between rs5744168 (TLR5), rs4986791 (TLR4), rs4986790 (TLR4), and rs3775291 (TLR3) polymorphisms and SLE susceptibility. Conclusions Our meta-analysis suggests that TLR7, TLR8, and TLR9 polymorphisms are associated with the development of SLE in Caucasian, Asian, and African populations. [ABSTRACT FROM AUTHOR]

Aims This study aimed to assess the relative efficacy and safety of tacrolimus, mycophenolate mofetil (MMF) and cyclophosphamide (CYC) as induction therapy for lupus nephritis. Methods Randomized controlled trials (RCTs) examining the efficacy and safety of tacrolimus, MMF and CYC for induction therapy in patients with lupus nephritis were included. We performed a Bayesian random-effects network meta-analysis to combine direct and indirect evidence from the RCTs. Results Nine RCTs including 972 patients met the inclusion criteria and pair-wise comparisons were performed, including 11 direct comparisons. Tacrolimus showed a significantly higher overall response rate (complete remission plus partial remission) than CYC (OR 2.35, 95% confidence interval (CI) 1.03–5.45), and was more efficacious than MMF (OR 1.60, 95% CI 0.70–3.57). MMF was superior to CYC in terms of overall response (OR 1.45, 95% CI 0.96–2.42). Ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that tacrolimus had the highest probability of being the best treatment for achieving the overall response (SUCRA = 0.9321), followed by MMF (SUCRA = 0.5385) and CYC (SUCRA = 0.0294). In terms of safety, tacrolimus showed the highest probability of decreasing the risk of serious infections (SUCRA = 0.9253), followed by MMF (SUCRA = 0.4027) and CYC (SUCRA = 0.1720). Conclusions Tacrolimus was the most efficacious induction treatment for patients with lupus nephritis, and had the highest probability of decreasing the risk of serious infections. Higher remission rates combined with a more favorable safety profile suggest that MMF is superior to CYC as induction treatment in these patients. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to determine whether the functional CD40 rs4810485 G/T polymorphism is associated with susceptibility to rheumatoid arthritis (RA) or with susceptibility to systemic lupus erythematosus (SLE). Methods A series of meta-analyses were conducted to test for association between the CD40 rs4810485 G/T polymorphism and RA or SLE. Results A total of 21 comparisons involving 15,095 patients and 27,050 controls for RA, and 1353 patients and 2342 controls for SLE were considered. Meta-analysis showed a significant association between the CD40 rs4810485 T allele and RA in all subjects (odds ratio (OR) 0.890, 95% confidence interval (CI) 0.846–0.936, p = 5.5 × 10−7). After stratification by ethnicity, the CD40 T allele was found to be significantly associated with RA in Europeans (OR 0.879, 95% CI 0.848–0.901, p = 3.0 × 10−9). A similar pattern of association was observed between the CD40 T allele and RA when the analysis was performed using the recessive, dominant, and additive models. Meta-analysis also showed a significant association between the CD40 polymorphism and SLE in Europeans (OR for the T allele 0.715, 95% CI 0.641–0.832, p = 1.4 × 10−6). Conclusions Our meta-analyses confirm that the CD40 rs4810485 G/T polymorphism is associated with susceptibility to RA and SLE in Europeans. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine whether the functional protein tyrosine phosphatase nonreceptor 22 (PTPN22) C1858T polymorphism (rs2476601) confers susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. A meta-analysis was conducted on the PTPN22 C1858T polymorphism across 11 comparative studies. Meta-analysis showed an association between the PTPN22 1858T allele and SLE in all study subjects (odds ratio (OR) 1.560, 95% confidence interval (CI) 1.336, 1.822, p = 2.0 × 10-8). Analysis after stratification by ethnicity indicated that the PTPN22 1858T allele was significantly associated with SLE in Europeans and Hispanics (OR 1.490, 95% CI 1.280, 1.735, p = 2.0 × 10-8; OR 2.355, 95% CI 1.644, 3.373, p = 2.9 × 10 -6). The meta-analysis showed that the C/T + T/T genotype was associated with susceptibility to SLE in all study subjects, Europeans, and Hispanics populations, and an association between the T/T genotype with SLE in Europeans. African Americans had a much lower prevalence of the T allele (2.2%) than any other population studied, and Europeans had the highest frequency (9.5%). In conclusion, this meta-analysis confirms that the PTPN22 C1858T polymorphism is associated with SLE susceptibility in different ethnic groups, and that its prevalence is ethnicity dependent. Lupus (2011) 20, 51—57. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the efficacies and toxicities of immunosuppressive treatments for lupus nephritis (LN) versus cyclophosphamide (CYC). A meta-analysis was performed to determine treatment efficacy and toxicity outcomes between mycophenolate mofetil (MMF) and CYC induction therapies, between MMF and azathioprine (AZA) as maintenance therapies, and between low-dose intravenous (IV) CYC and high-dose IV CYC therapy. Ten randomized controlled trials (RCTs) were included in the meta-analysis. In terms of induction therapies, MMF did not increase complete remission or partial remission rates as compared with CYC. However, the relative risks (RRs) of amenorrhea and leukopenia tended to be lower in the MMF group than in the CYC group. Meta-analysis of MMF versus AZA as a maintenance therapy showed no difference between the two groups in terms of response rates or the risk of developing end-stage renal disease. Low-dose IV CYC therapy had lower relapse rates than high-dose IV CYC therapy (RR 0.465, 95% confidence interval [CI] 0.261-0.830, p-value 0.010), and was associated with a lower infection risk (RR 0.688, 95% CI 0.523-0.905, p-value 0.008). In conclusion, MMF was found to be as effective as CYC and tended to have a better safety profile as an induction therapy for LN than CYC. [ABSTRACT FROM AUTHOR]

The aim of this study was to explore whether polymorphisms of the Fcγ receptors (FcγRs) IIB T/I232 and FcγRIIIB NA1/NA2, confer susceptibility to systemic lupus erythematosus (SLE) and lupus nephritis (LN). The authors conducted a meta-analysis on associations between the FcγRIIB T/I232 and FcγRIIIB NA1/NA2 polymorphisms and SLE and LN susceptibility as determined using 1) allele contrast, 2) recessive, 3) dominant models and 4) contrast of homozygotes. A total of 16 separate comparisons were considered, consisting of 2887 SLE patients and 3105 controls. Meta-analysis of the FcγRIIB T/I232 polymorphism showed a significant association between the FcγRIIB T allele and the risk of developing SLE compared with the FcγRIIB I allele (OR = 1.207, 95% CI = 1.061-1.373, P = 0.004). In subjects of Asian descent, a significant association was observed between the FcγRIIB T allele and SLE (OR = 1.332, 95% CI 1.138-1.558, P < 0.001). However, in Europeans no such association was found. In contrast, no association was found between SLE or LN and the FcγRIIIB NA1/NA2 polymorphism in all subjects, or in European and Asian populations. This meta-analysis shows that the FcγRIIB T/I232 polymorphism confers susceptibility to SLE, especially in Asian-derived populations. [ABSTRACT FROM AUTHOR]

Programmed cell death 1 (PDCD1 or PD1) polymorphisms have been inconsistently reported to be associated with systemic lupus erythematosus (SLE). The aim of this study was to explore whether the PDCD1 polymorphisms confer a susceptibility to SLE and lupus nephritis (LN).We conducted a meta-analysis on the association of PDCD1 polymorphisms with SLE in overall and specific ethnic populations. A total of 15 separate comparisons were included in this meta-analysis consisting of nine Europeans, two Latin Americans, two Africans, one Asian and one unknown participant. In subgroup analysis, the PD1.3A allele was significantly associated with SLE in Latin Americans (OR = 3.073, 95% CI = 1.416-6.461, P = 0.003), but not in patients of European and African decent. The PD1.3A allele was a risk factor for LN in European descendants (OR = 2.207, 95% CI = 1.488-3.467, P < 0.001). The PD1.5C allele was a risk factor for SLE in Europeans (OR = 1.297, 95% CI = 1.024-1.643, P = 0.031). In conclusion, this meta-analysis demonstrated an association of the PD1.3A allele with LN in European and SLE in Latin-American populations. Furthermore, the PD1.5C allele was associated with SLE susceptibility in Europeans. [ABSTRACT FROM AUTHOR]