Prevalence of polymyxin-resistant bacterial strains in India: a systematic review and meta-analysis.

INTRODUCTION: Polymyxins, the cationic lipopeptide antibiotics, are the last line of therapeutics against the MDR Gram-negative bacterial (GNB) pathogens. Unfortunately, the rising cases of polymyxin-resistant strains from across the globe have adversely impacted their utility. While the molecular mechanisms responsible for developing polymyxin resistance (PolR) are largely understood, the prevalence of PolR strains in India has not been investigated systematically. The current study was undertaken to primarily determine the prevalence of PolR strains in India. Moreover, the extent of the spread of mobile colistin resistance (mcr) genes among the GNB strains in India was also determined. METHOD: A systematic search for articles using the relevant inclusion and exclusion criteria was performed in the applicable databases for the period January 2015 to December 2023. The included 41 studies were subjected to a meta-analysis using the Comprehensive Meta-Analysis software (V4.0). Publication biases were assessed using funnel plots and Egger's regression analysis. RESULT: Considering a total of 41 studies including 24 589 bacterial isolates the present meta-analysis found the rate of PolR bacteria in India to be at 15.0% (95% CI: 11.2 to 19.8). Among the Indian States, Tamil Nadu topped with the highest prevalence of PolR at 28.3%. Investigating the contribution of the mcr genes, it was observed that among the PolR strains, 8.4% (95% CI: 4.8 to 14.3) were mcr positive. CONCLUSION: The study determined the prevalence of PolR strains in India at 15.0%, which is higher than that of the global average at 10%. The study also determined that 8.4% of the PolR strains carried the mcr genes. The mcr-positive strains reported from India could be an underestimation of the actual numbers due to the non-inclusion of mcr screening in many previous studies. This study provides insight into the state of the PolR situation in India, which may be useful to develop a monitoring strategy to contain the spread of such strains and preserve the efficacy of the polymyxins.

Maintaining ethics, Integrity, and accountability: Best practices for reporting a meta-analysis.

This letter addresses the significance of conducting and reporting systematic reviews and meta-analyses using the appropriate methods. It also highlights the importance of implementing the latest guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-2020, which ensures the maintenance of ethics, integrity, and accountability while reporting systematic reviews and meta-analyses.

Association of Interleukin 23 Receptor Polymorphisms with Predisposition to Rheumatoid Arthritis: An Updated Meta and Trial Sequential Analysis.

The etiology of Rheumatoid Arthritis (RA) development remained unclear, and several factors, such as environmental, genetic, and immune system dysfunction, have been attributed to the susceptibility. Interleukin 23 (IL23) induces expansion of the Th17 cells through the IL-23 receptor (IL-23R) and believes in playing a major role in RA pathogenesis. Various genetic mutants in the IL23R gene (rs10489629, rs1343151, rs2201841, rs7517847, rs1004819, rs10889677, rs11209026, rs7530511) have been associated with the susceptibility RA, but results are contradictories. We performed a meta-analysis to establish the association of IL23R polymorphisms with susceptibility RA. For the meta-analysis, a detailed search of databases like Google Scholar, PubMed, Scopus, Web of Science, and Science Direct was conducted, and data were extracted from the included reports. The meta-analysis was performed by the Comprehensive Meta-Analysis v3 software. A significant association of IL-23R rs11209026 (AA vs. GG: Odds ratio = 2.250, p-value = 0.01; AA vs. GG+GA: Odds ratio = 2.271, p-value = 0.01), rs1343151 (A vs. G: Odds ratio = 1.091, p-value = 0.001; AA vs. GG: Odds ratio = 1.209, p-value = 0.001; GA vs. GG: Odds ratio = 1.116, p-value = 0.004; AA+GA vs. GG: Odds ratio = 1.135, p-value = 0.000; AA vs. GG+GA: Odds ratio = 1.144, p-value = 0.012) and rs10889677 (CA vs. CC: Odds ratio = 1.375, p-value = 0.041) polymorphisms were observed with increased susceptibility for the development of RA. In contrast, IL-23R rs10489629 (G vs. A: odds ratio = 0.901, p-value = 0.047, GG vs. AA: Odds ratio = 0.763, p-value = 0.022, GG vs. AA+AG: Odds ratio = 0.852, p-value = 0.00) and IL23R rs2201841 (CC vs. TT+TC: Odds ratio = 0.826, p-value = 0.026) variants were linked with protection against the development of RA. In addition, the trial sequential analysis revealed the inclusion of a sufficient number of studies in the present meta-analysis, and no further additional studies are required. IL-23R variants are associated with genetic susceptibility or resistance against the development of RA.

Efficacy of baricitinib for the treatment of systemic lupus erythematosus patients: A meta-analysis of randomized controlled trials.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal autoantibody production, inflammation, and organ damage. Most SLE treatment strategies aim to induce remission or reduce disease activity while avoiding flares. Baricitinib has been used effectively to manage various inflammatory diseases, and some randomized controlled trials (RCT) have shown that it is beneficial in treating SLE. The current study aims to assess the efficacy of baricitinib in treating SLE patients. MATERIALS AND METHODS: Various databases such as PubMed, Scopus, and Science Direct were searched to obtain eligible studies for the present meta-analysis. Data such as baseline characteristics of patients, doses of the baricitinib, follow-up duration, and treatment outcome in the form of SLE responder index-4 (SRI-4) and lupus low disease activity state (LLDAS) were extracted. Combined odds ratio, 95% confidence interval, and probability values were calculated to study the efficacy of baricitinib in treating SLE patients. A p-value less than .05 was taken as significant. Comprehensive meta-analysis v3 was used for all analyses. RESULTS: Three articles were found eligible for the present meta-analysis comprising 614 patients with placebo, 614 SLE patients receiving 4 mg, and 621 patients with 2 mg of baricitinib. Meta-analysis revealed a beneficial effect of 4 mg baricitinib in SLE patients compared to placebo, as measured by an increase in the SRI-4 (p = .006, OR = 1.370) and LLDAS (p = .083, OR = 1.252) rates. In contrast to the placebo group, however, patients receiving 2 mg of baricitinib exhibited no significant improvement. The trial sequential analysis revealed the need for additional RCTs to determine the role of baricitinib in treating SLE patients. CONCLUSION: In treating SLE patients, administrating a higher dose of baricitinib (4 mg) may be effective. However, additional RCTs in different populations with larger sample sizes are required to validate our findings.

Association of Toll-Like Receptor 7 (TLR7) Polymorphisms with Predisposition to Systemic Lupus Erythematosus (SLE): A Meta and Trial Sequential Analysis.

Systemic Lupus Erythematosus (SLE) is an autoimmune disorder characterized by autoantibody production and organ involvement. The role of toll-like receptor-7 in SLE is well established. Although genetic variations in the TLR-7 gene have been associated with an increased risk of developing SLE, the findings are not consistent. We performed a meta-analysis of previously published articles on four important single nucleotide polymorphisms in the TLR-7 gene (rs3853839, rs179008, rs179019, and rs179010) to reach a valid conclusion. Various literature databases, including PubMed, Science Direct, and Scopus, were scoured for eligible reports until May 10, 2023. GPower software v.3 was used to assess the power of individual reports included in the meta-analysis. Comprehensive Meta-analysis v3 software was used to perform all statistics. The publication biases in each genetic comparison model were investigated using funnel plots and Egger's regression test. To test heterogeneity, Cochrane Q statistics, probability value and I2 were used. Considering the predefined inclusion and exclusion criteria, the current study included a total of 10 eligible studies that included 15,472 SLE cases and 16,721 healthy controls. The meta-analysis revealed a significant association between TLR7 polymorphisms (rs179019 and rs179010) and susceptibility to SLE development. Other TLR7 polymorphisms (rs3853839 and rs179008), on the other hand, showed no significant association. Furthermore, the trial sequential analysis identified the need for additional case control studies for TLR-7 polymorphisms (rs3853839, rs179008, and rs179019) other than the rs179010 polymorphism. TLR7 variants for rs179010 and rs179019 are risk factor for the development of SLE. Further investigations are required to reach a valid conclusion.

Procalcitonin is elevated in severe malaria and is a promising biomarker of severe malaria and multi-organ dysfunction: A cross-sectional study and meta-analysis.

BACKGROUND: Elevated procalcitonin (PCT) has been reported in bacterial infection and is positively associated with the severity of the disease. Patients with severe Plasmodium falciparum malaria also display higher procalcitonin levels compared to those with non-severe disease, indicating a possible role for bacterial infection in severe disease, however this observation remained variable in different study population. Furthermore, the significance of PCT in different clinical categories of severe malaria has not been evaluated so far. METHODS: A total of 74 P. falciparum-infected subjects were enrolled in the study comprising of 55 cases complicated malaria [cerebral malaria- 14; non-cerebral severe malaria- 21; multi-organ dysfunction- 20] and 19 uncomplicated cases. Serum levels of PCT were quantified by fluorescence immunoassay. For meta-analysis, the literature search was performed in different databases, and all relevant articles were screened, and eligible reports were identified based on predefined inclusion and exclusion criteria. The meta-analysis was performed by comprehensive meta-analysis software V3 and MedCalc 20.218. RESULTS: Patients with severe P. falciparum malaria had significantly higher PCT levels compared to uncomplicated cases (p = 0.01). Analysis of PCT in different categories of patients with severe malaria revealed significantly elevated PCT in multi-organ dysfunctions compared to those with uncomplicated malaria (p = 0.004) and cerebral malaria (p = 0.05). Interestingly the receiver operating characteristics curve analysis showed procalcitonin as a promising biomarker for differentiating severe malaria (AUC: 0.697, p = 0.01) and multi-organ dysfunction (AUC: 0.704, p = 0.007) from uncomplicated malaria and other clinical categories of falciparum malaria, respectively. Furthermore, meta-analysis also revealed an elevated procalcitonin in severe malaria and it could be an important biomarker in the management of severe disease. CONCLUSIONS: PCT is elevated in P. falciparum-infected patients and could be a good biomarker for diagnosis of severe malaria and multi-organ dysfunction. It can help in the management of severe disease with additional treatment options.

Prevalence of migraine in systemic lupus erythematosus: A meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder with a wide range of clinical manifestations, including neurological issues in about 25%-75% of cases. Among the neurological involvement cases, most cases show migraine. However, the prevalence of migraine varied worldwide, and in some studies, a higher incidence of migraine in SLE cases was reported compared to healthy controls. In the present study, we adopted a meta-analysis approach to find out the prevalence of migraine in SLE patients worldwide and investigate whether migraine frequency is more prevalent in SLE patients than controls. MATERIAL AND METHODS: Various literature databases such as Scopus, PubMed, Science Direct, and Google Scholar were screened for eligible studies. The last search was performed on January 21, 2023. Publication biases were accessed by Egger's regression analysis and funnel plots. Cochrane Q statistics and I2 values explored the presence or absence of heterogeneity. All statistical analysis of meta-analysis was performed in comprehensive meta-analysis software v3. RESULTS: Based on predefined inclusion and exclusion criteria, 17 reports comprising 2901 SLE patients and 575 healthy controls were considered in the present study. The meta-analysis revealed the prevalence of migraine to be 34.8%. Furthermore, migraine was more prevalent in SLE patients than healthy controls (OR: 1.964, p = 0.000, 95% CI = 1.512-2.550). Similar trends were also observed while considering another 10 independent reports those were not disclosed about the migraine diagnosis criteria (number of reports: 27, SLE: 3473, HC: 741, prevalence: 33.5%, SLE vs HC: OR = 2.107, p = 0.000, 95% CI = 1.672-2.655). Subgroup analysis demonstrated that SLE patients from South America had a higher prevalence of migraine (56.2%). CONCLUSIONS: About one-third of SLE patients experience migraine worldwide. The prevalence of migraine is more frequent in SLE patients than the healthy controls.

Differential differentiation of B cell lymphopoiesis in lethal and non-lethal murine malaria models.

B cells in protection against malaria and need of experiencing many episodes in humans to achieve a state of immunity is largely unknown. The cellular basis of such defects in terms of B cell generation, maturation and trafficking was studied by taking Plasmodium chabaudi, a non-lethal and Plasmodium berghei, a lethal murine model. A flow cytometry (FCF) based evaluation was used to study alterations in generation and maintenance of B cells in patients with Plasmodium falciparum malaria as well as in murine malaria models. A significant accumulation of mature B cells in bone marrow and immature B cells in circulation was a feature observed only in lethal malaria. At peak parasitaemia, both the models induce a significant decrease in T2 (transitional) B cells with expansion of T1B cells. Studies in patients with acute Pf malaria showed a significant expansion of memory B cells and TB cells with a concomitant decrease in naive2 B cells as compared with healthy controls. This study clearly demonstrates that acute malarial infection induces major disturbances in B cell development in lymphoid organs and trafficking in periphery.

A Drug Repurposing Approach to Identify Therapeutics by Screening Pathogen Box Exploiting SARS-CoV-2 Main Protease.

Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2) and is responsible for a higher degree of morbidity and mortality worldwide. There is a smaller number of approved therapeutics available to target the SARS-CoV-2 virus, and the virus is evolving at a fast pace. So, there is a continuous need for new therapeutics to combat COVID-19. The main protease (Mpro ) enzyme of SARS-CoV-2 is essential for replication and transcription of the viral genome, thus could be a potent target for the treatment of COVID-19. In the present study, we performed an in-silico screening analysis of 400 diverse bioactive inhibitors with proven antibacterial and antiviral properties against Mpro drug target. Ten compounds showed a higher binding affinity for Mpro than the reference compound (N3), with desired physicochemical properties. Furthermore, in-depth docking and superimposition revealed that three compounds (MMV1782211, MMV1782220, and MMV1578574) are actively interacting with the catalytic domain of Mpro . In addition, the molecular dynamics simulation study showed a solid and stable interaction of MMV178221-Mpro complex compared to the other two molecules (MMV1782220, and MMV1578574). In line with this observation, MM/PBSA free energy calculation also demonstrated the highest binding free energy of -115.8 kJ/mol for MMV178221-Mpro compound. In conclusion, the present in silico analysis revealed MMV1782211 as a possible and potent molecule to target the Mpro and must be explored in vitro and in vivo to combat the COVID-19.

Cytotoxic T-lymphocyte associated protein 4 (CTLA4) polymorphisms are linked to systemic lupus erythematosus: an updated meta-analysis.

Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) molecule controls T cell immune response. Functional single nucleotide polymorphisms (SNPs) in the CTLA-4 gene have been associated with several autoimmune diseases, including systemic lupus erythematosus (SLE).  However, the genetic association of the CTLA-4 variants with vulnerability to SLE remained contradictory. We have conducted a current meta-analysis by combining the findings of prior published articles in order to make a conclusive statement. Various literature databases were screened with appropriate keywords to obtain relevant articles, and eligible reports were obtained using well-defined inclusion and exclusion criteria. Meta-analysis was performed by Comprehensive Meta-analysis V 3.3, and various statistical parameters such as odds ratio, 95% confidence interval, and probability values were computed. A total of 3847 SLE patients and 5278 healthy controls were considered in the present meta-analysis from 26 individual reports. A significant association of CTLA-4 +49 A/G (G vs. A: p=0.03, OR=1.47) and -1722 T/C (p=0.02, OR=0.87) polymorphisms were observed with susceptibility and resistance against the development of SLE, respectively. However, the other two SNPs in the CTLA-4 gene (-318 C/T and -1661 A/G) failed to establish a connection. Interestingly, subgroup analysis revealed an association of CTLA-4 +49 A/G with a predisposition to SLE only in the Asian population (G vs. A: p=0.04, OR=1.26, GG vs. AA: p=0.02, OR=1.84, AG vs AA: p=0.01, OR=1.44, GG+AG vs AA: p=0.01, OR=1.52) and not in Caucasians. The current meta-analysis suggests a significant CTLA-4 +49 A/G variant association with susceptibility to SLE development in overall and Asian populations. In contrast, the other variant, -1722 T/C, is linked with protection against SLE. However, further case-control studies in diverse ethnic populations are requisite.

Interferon-gamma (IFN-γ) intronic variant (rs2430561) is a risk factor for systemic lupus erythematosus: Observation from a meta-analysis.

BACKGROUND: The role of interferon-gamma (IFN-γ) in autoimmune disorders has been well documented. Elevated levels of IFN-γ are observed in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and are linked with disease severity. Single nucleotide polymorphism in the intronic region of the IFN-γ gene (+874 T>A rs2430561) has been associated with susceptibility to the development of RA and SLE; however, the reports remained contradictories. We conducted a meta-analysis using earlier published articles to reach a valid conclusion on the role of IFN-γ polymorphism (+874 T>A) in autoimmune diseases. MATERIALS AND METHODS: Various online databases such as PubMed, Google Scholar, Science Direct, and Scopus were searched to find eligible reports for inclusion in the present analysis. Two independent authors extracted eligible studies and data. The meta-analysis was performed by comprehensive meta-analysis software (CMA) v.3.1. Trial sequential analysis was performed to test whether enough case-control studies have already been conducted worldwide to reach a valid observation. RESULTS: Six published reports on the role of IFN-γ +874 T>A in SLE and four in RA were found after searching various databases. However, out of those six studies in SLE, in one study, the distribution of genotypes was not following the hardy-Weinberg equilibrium. In RA, three studies were deviated out of four reports. Thus, a total of five studies comprising 1440 SLE patients and 1748 controls were considered for the present meta-analysis. Meta-analysis showed a significant association between IFN-γ +874 T>A variants with susceptibility to SLE (homozygous comparison: p = 0.036, OR = 1.592, heterozygous model: p = 0.042, OR = 1.507, dominant model: p = 0.002, OR = 1.309). CONCLUSIONS: IFN-γ +874 T>A variant is associated with predisposition to SLE development.

Polymorphisms and haplotypes of TLR-4/9 associated with bacterial infection, gingival inflammation/recession and oral cancer.

BACKGROUND: The expression and SNPs of innate immunity genes TLR-4/9 for bacterial infection, gingival inflammation/gingival recession (GIGR), and oral squamous cell carcinoma (OSCC) are largely unknown. PATIENTS AND METHOD: 235 specimens (120 OSCC cases, among which 85 cases with either Porphyromonas gingivalis, Fusobacterium nucleatum or Treponema denticola infection and GIGR) and 115 healthy controls were used to know the expression and polymorphisms (TLR-4: N1:rs10759931, N2:rs11536889, N3:rs1927911, N4:rs4986790; TLR-9: N5:rs5743836, N6:rs352140, N7:rs187084 and N8:rs352139) of TLR-4/9 by western blot, RT-PCR, and allele-specific (AS)-PCR followed by sequencing. RESULTS: Increased TLR-4/9 mRNA/protein expression, bacterial infection (BI) and GIGR were associated with OSCC incidence. One of the three BI and GIGR was observed in 70.83% of OSCC cases, whereas all the HC used were free from any of these three BI/GIGR. The N3: CT-genotype (Odds Ratio hereafter as O.R.=1.811, p = 0.0338), TT-genotype (O.R.=3.094, p = 0.0124), 'T'-allele (O.R.=1.821, p = 0.003), N4: AG-genotype (O.R.=2.015, p = 0.0222) and 'G'-allele (O.R.=1.86, p = 0.018) of TLR-4 as well as the N5: CC-genotype (O.R.=3.939, p = 0.0017), 'C'-allele (O.R.=1.839, p = 0.0042), N6: AA-genotype (O.R.=2.195, p = 0.0234), 'A'-allele (O.R.=1.569, p = 0.0163), N7: TC-genotype (O.R.=2.083, p = 0.0136), CC-genotype (O.R.=2.984, p = 0.003) and 'C'-allele (O.R.=1.885, p = 0.0008) of TLR-9 were associated with increased OSCC risk. Similarly, the N2:'C'-allele (O.R.=1.615, p = 0.0382), N3: TT-genotype (O.R.=2.829, p = 0.0336), 'T'-allele (O.R.=1.742, p = 0.0115), N4: AG-genotype (O.R.=2.221, p = 0.0147) and 'G'-allele (O.R.=1.890, p = 0.0238) of TLR-4 as well as the N5: CC-genotype (O.R.=2.830, p = 0.031), N6: AA-genotype (O.R.=2.6, p = 0.0122) and 'A'-allele (O.R.=1.746, p = 0.0064), N7:CC-genotype (O.R.2.706, p = 0.0111) and 'C'-allele (O.R. 1.774, p = 0.0055) of TLR-9 were correlated with GIGR and BI. TLR-4 (N1-N2-N3-N4: A-C-T-A (O.R.=2.1, p = 0.0069) and TLR-9 (N5-N6-N7-N8: T-A-C-A (O.R.=2.019, p = 0.0263); C-A-C-A (O.R.=6.0, p = 0.0084); C-A-C-G (O.R.=4.957, p = 0.0452) haplotypes were linked with OSCC vulnerability, while the TLR-4 (N1-N2-N3-N4: G-C-C-A (O.R.=0.5752, p = 0.0131) and TLR-9 (N5-N6-N7-N8: T-G-T-A (O.R.=0.5438, p = 0.0314); T-G-T-G (O.R.=0.5241, p = 0.036) haplotypes offered protection. CONCLUSION: TLR-4/9 expression, polymorphisms, and BI-induced GIGR could increase OSCC risk. This may be used in pathogenesis and oral cancer prediction.

Toll-like receptor-2 (TLR-2) rs111200466 variant offers protection against SARS-CoV-2 infections and mortality: a worldwide epidemiological correlation analysis.

Recently Toll-like receptor-2 has been shown to sense the envelope protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and initiate the production of inflammatory molecules. The expression and function of the TLR2 has been associated with several functional polymorphisms such as a 23 bp ins/del (rs111200466), Arg677Trp (rs121917864), and Arg753Gln (rs5743708). In the present study, we hypothesized that the TLR2 common functional variants would be associated with the worldwide incidence and mortality rate of SARS-CoV-2. The frequency of TLR2 polymorphisms and coronavirus disease-19 (COVID-19) were acquired from multiple databases, including genomAD, 1000 genome, dbSNP, and worldometer, respectively. The Spearman rank correlation coefficient analysis revealed a significant inverse correlation between the del allele of rs111200466 polymorphism with susceptibility to SARS-CoV-2 infection and related mortality at different times. In conclusion, the TLR2 rs111200466 minor allele (del) may be linked with susceptibility to SARS-CoV-2 infections and bad outcomes. However, further case-control studies in different populations are required to validate our observations.

TNF-α promoter variant (G-308A) is associated with susceptibility to P. falciparum infection and severe malaria: a meta-analysis and trial sequential analysis.

Tumor necrosis factor-alpha (TNF-α) plays an essential role in Plasmodium falciparum infection, with lower levels associated with susceptibility to infection and higher levels linked with organ failure in severe malaria. Genetic polymorphisms in the promoter region of the TNF-α gene (G-308A and G-238A) affect plasma TNF-α levels. Numerous case-control studies have been conducted to determine the possible association between TNF-α polymorphisms and susceptibility to malaria infection and clinical severity; however, the results are inconsistent. Various databases such as Google Scholar, Science Direct, PubMed, and Scopus were searched for relevant articles for the present meta-analysis. Data were extracted from the eligible studies based on inclusion and exclusion criteria. Meta-analysis was carried out with CMA v.3.3.070 software, and combined odds ratio, 95% confidence interval, and p values were calculated. Further, a trial sequential analysis was also performed to test whether enough number of case and controls have been enrolled to date to draw a valid conclusion. Allele (OR = 9.757, p value=.049) and heterozygous (OR = 8.98, p value=.016) comparison model revealed the TNF-α G-308A variant as a susceptible genetic factor for P. falciparum infection. Similarly, a significant association of TNF-α G-308A polymorphism with P. falciparum malarial severity was also observed (A versus G: OR = 1.761, p value = .000; and GG + GA versus GG: OR = 1.769, p value = .000). However, no association of TNF-α (G-238A) polymorphism was observed with infection and severity of P. falciparum or Plasmodium vivax malaria. TNF-α G-308A variant is associated with susceptibility to P. falciparum infection and clinical severity. However, further studies on different populations are required.

The role of MBL, PCT, CRP, neutrophil-lymphocyte ratio, and platelet lymphocyte ratio in differentiating infections from flares in lupus.

BACKGROUND: The distinction between infection and flare in systemic lupus erythematosus (SLE) has always been a dilemma for clinicians as the clinical and biochemical profiles overlap. The present study evaluated affordable biomarkers to distinguish infection from flare in an SLE cohort in a tertiary care center in eastern India. METHODS: One hundred and fifty-two SLE patients were clinically evaluated and enrolled in the present study. Hematological, immunological, and biochemical profiles and various biomarkers such as C reactive protein (CRP), procalcitonin (PCT), and Mannose-binding lectin (MBL) were quantified. RESULTS: One hundred and fifty-two patients (152) were enrolled in the present study and all had SLEDAI scores of more than 4. From which 70 had infection, and the common infections were urinary tract infection (34.28%) followed by pneumonia (27.14%). Neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP) were significantly elevated in SLE with infections (NLR: 5.84 ± 2.47; CRP: 30.56 ± 41.63) than those with flare (NLR: 3.87 ± 2.62; CRP: 8.73 ± 9.53). The receiver operating characteristic curve (ROC) analysis revealed CRP, PLR, and NLR as important markers for predicting infections (CRP: AUC = 0.682, p = 0.0001; PLR: AUC = 0.668, p = 0.0008; NLR: AUC = 0.742, p < 0.0001). The MBL and PCT levels were comparable among SLE flare and those with infections. CONCLUSIONS: NLR and CRP levels are affordable biomarkers to distinguish infections from flares in SLE. MBL and PCT could not differentiate flare from an infection. Key Points • Biomarkers for the differentiation of infection and flare in SLE are limited. • NLR, PLR, and CRP are promising biomarkers to enable differentiation. • PCT and MBL are not ideal biomarkers to differentiate infection from flare.

Role of interleukin-6 and interferon-α in systemic lupus erythematosus: A case-control study and meta-analysis.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disorder affecting various organ systems with unknown etiology. Interleukin-6 (IL-6) and interferon-alpha (IFN-α) have been shown to have a major role in disease pathogenesis, and they correlate with SLE disease activity, but reports in the literature are conflicting. The present study aims to investigate the significance of IL-6 and IFN-α levels in SLE pathogenesis in an eastern Indian cohort. MATERIAL AND METHODS: 70 SLE patients fulfilled SLICC 2012 criteria, and 40 age- and gender-matched healthy controls (HC) were enrolled. Baseline characteristics along with disease activity were recorded for all patients. Levels of IL-6 and IFN-α were measured by using ELISA. For the meta-analysis, published articles were searched through different databases. Two independent researchers extracted data, and the meta-analysis was performed with CMA v3.1. RESULTS: The plasma levels of IL-6 and IFN-α in SLE patients were significantly elevated compared to HC (IL-6: p < .0001, IFN-α: p = 0.01). SLEDAI score correlated positively with plasma IL-6 (p < .0001, r = 0.46) and IFN-α levels (p < .0001; r = 0.47). Meta-analysis of previous reports, including our case-control data, revealed higher IL-6 (p < .0001) and IFN-α (p = .005) in SLE patients compared to HC. Furthermore, IL-6 (p < .0001, r = 0.526) and IFN-α (p < .0001; r = 0.371) levels positively correlated with the disease activity. CONCLUSION: IL-6 and IFN-α levels are elevated in SLE and they correlate with disease activity. Further studies with a larger sample size in different populations are required to validate our findings.

Interleukin 17A rs2275913 polymorphism is associated with susceptibility to systemic lupus erythematosus: A meta and trial sequential analysis.

BACKGROUND: The role of cytokines in the development of systemic lupus erythematosus (SLE) has received much attention. Interleukin-17 A upregulates several inflammation-related genes and is thought to have a crucial role in SLE development. The susceptibility to SLE development has been linked to functional genetic variations of the IL-17A gene; nevertheless, the findings have been conflicting. We conducted a meta-analysis that included previously published reports to establish a definitive conclusion on the role of the IL-17A rs2275913 polymorphism in SLE propensity. MATERIALS AND METHODS: The PubMed, Google Scholar, and Scopus databases were used to find eligible published articles. All analyses were conducted using Comprehensive Meta-analysis V3.1. Funnel plots and Egger's regression analysis were used to assess publication bias. Q statistics and I2 test explored the heterogeneity among the included studies. Combined odds ratio, 95% confidence interval were calculated for each comparison model. RESULTS: Based on the inclusion and exclusion criteria, a total of four reports, comprising of 608 SLE patients and 815 healthy controls, were considered for the present meta-analysis. The homozygous comparison (AA vs. GG: combined odds ratio= 2.046, p = 0.005) and recessive genetic model (AA vs. GG+GA: combined odds ratio=1.901, p = 0.010) analysis revealed a significant association of rs2275913 with susceptibility to the development of SLE. However, other genetic comparisons (A vs. G, GA vs. GG, AA+GA vs. GG) failed to demonstrate such association. Furthermore, trial sequential analysis revealed a sufficient number of studies, including enough cases and controls that have already been considered to conclude the role of IL17-A rs2275913 polymorphism in SLE. CONCLUSIONS: IL-17A rs2275913 polymorphism is associated with susceptibility to SLE development.