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BackgroundSystemic 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 Methods70 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.ResultsThe 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.ConclusionIL-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.

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.

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.

Tumor necrosis factor-alpha (TNF-α) plays an essential role in

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.

Recently, we reported oligoadenylate synthetase 1 (OAS1) contributed to the risk of Alzheimer’s disease, by its enrichment in transcriptional networks expressed by microglia. However, the function of OAS1 within microglia was not known. Using genotyping from 1313 individuals with sporadic Alzheimer’s disease and 1234 control individuals, we confirm the OAS1 variant, rs1131454, is associated with increased risk for Alzheimer’s disease. The same OAS1 locus has been recently associated with severe coronavirus disease 2019 (COVID-19) outcomes, linking risk for both diseases. The single nucleotide polymorphisms rs1131454(A) and rs4766676(T) are associated with Alzheimer’s disease, and rs10735079(A) and rs6489867(T) are associated with severe COVID-19, where the risk alleles are linked with decreased OAS1 expression. Analysing single-cell RNA-sequencing data of myeloid cells from Alzheimer’s disease and COVID-19 patients, we identify co-expression networks containing interferon (IFN)-responsive genes, including OAS1, which are significantly upregulated with age and both diseases. In human induced pluripotent stem cell-derived microglia with lowered OAS1 expression, we show exaggerated production of TNF-α with IFN-γ stimulation, indicating OAS1 is required to limit the pro-inflammatory response of myeloid cells. Collectively, our data support a link between genetic risk for Alzheimer’s disease and susceptibility to critical illness with COVID-19 centred on OAS1, a finding with potential implications for future treatments of Alzheimer’s disease and COVID-19, and development of biomarkers to track disease progression.

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.

Background: Novel coronavirus disease-19 (COVID-19) has spread worldwide, and to date presence of the virus has been recorded in 215 countries contributing 0.43 million of death. The role of blood groups in susceptibility/resistance to various infectious diseases has been reported. However, the association of blood groups with susceptibility to COVID-19 infections or related death are limited. In the present report, we performed an epidemiological investigation in the Indian population to decipher the importance of blood groups concerning susceptibility or mortality in COVID-19 infection. Materials and Methods: Data on COVID-19 infection and mortality was obtained from the website of the Government of India. Prevalence of ABO blood groups in different states and union territories of India were searched using different databases such as PubMed and Google Scholar. Relevant articles were downloaded, and data were extracted. Spearman’s rank coefficient analysis was employed to study the correlation between blood group frequencies and COVID-19 infection or mortality rate. Results: A significant inverse correlation was observed between the frequency of O blood group and the COVID-19 mortality rate (Spearman r = -0.36, P=0.03), indicating a possible protective role of O blood group against COVID-19 related death. In contrast, the prevalence of blood group B was positively correlated with COVID-19 death/million (Spearman r = 0.67, P

Highlights • Differential distributions of vitamin D were observed in the Indian population. • Vitamin D levels was inversely correlated with SARS-CoV-2 infection rate. • COVID-19 mortality rate was negatively associated with mean vitamin D levels., Background The role of vitamin D in the susceptibility and severity of various viral diseases has been well documented. Recently, some reports highlighted the possible importance of vitamin D in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although India receives adequate sunlight throughout the year, the majority of Indians are deficient in vitamin D levels. In the present study, we hypothesized that vitamin D deficiency would be associated with the SARS-CoV-2 infection rate and mortality in the Indian population. Materials and methods SARS-CoV-2 infection and mortality data were obtained from the Government of India's official website (accessed on 16th August 2020). Various literature databases like PubMed and Google Scholar were searched to find the mean of 25-hydroxyvitamin D [25(OH)D] levels in different states and union territories of India, Pearson correlation was carried out to investigate the possible link between mean 25(OH)D levels and SARS-CoV-2 infection and mortality per million of the population. Results An inverse correlation was observed between the mean level of 25(OH)D and SARS-CoV-2 infection rate (r = −0.43, p = 0.02) and mortality rate (r = −0.42, p = 0.02). Conclusions The present observational study revealed an association of vitamin D with SARS-CoV-2 infection and related mortality. Further studies are required to validate our observations.

Objectives Mannose-binding lectin (MBL), an essential innate immune molecule, enhances the opsonization process and activates the complement system. Genetic variations at the promoter and coding region of the MBL-2 gene have been associated with susceptibility to systemic lupus erythematosus (SLE); however, reports remained inconsistent. The present study performs a meta-analysis of published peer-reviewed articles to draw a definitive conclusion. Materials and Methods Published peer-reviewed articles on the association of MBL-2 gene polymorphisms and SLE were screened on various databases such as PubMed (Medline), ScienceDirect, and Google Scholar. A total of 23 eligible articles were included in the present study, comprising 3074 SLE patients and 3985 controls. Genotype and/or allele data for MBL-2 polymorphisms (A > B, A > C, A > D, A > O, Y > X and H > L) were extracted and analyzed by Comprehensive Meta-Analysis software (CMA V3.1). Results The overall analysis revealed a significant association of MBL-2 (A > O) polymorphism with a predisposition to SLE in allele contrast ( p = 0.000; OR = 1.261), homozygous ( p = 0.005; OR = 1.482), heterozygous ( p = 0.004; OR = 1.247), dominant ( p = 0.000; OR = 1.303) and recessive ( p = 0.025; OR = 1.356) genetic comparison model. Similar results were also observed in the comparison of allele and the dominant genetic model of MBL-2 (A > B) polymorphism in overall (allele: p = 0.000, OR = 1.46, dominant: p = 0.001, OR = 1.31) and in the Asian cohorts (allele: p = 0.007, OR = 1.43, dominant: p = 0.008, OR = 1.32). Interestingly, MBL-2 (Y-221X) polymorphism exhibited protection against the development of SLE in heterozygous ( p = 0.005, OR = 0.619) and dominant genetic comparison ( p = 0.01, OR = 0.672) models. Conclusions MBL-2 variants (A > O and A > B) are associated with predisposition to SLE. Conversely, promoter polymorphism (Y-221X) offers protection against SLE development.

Supplemental material, sj-pdf-6-lup-10.1177_0961203320939156 for Association of MBL-2 gene polymorphisms with systemic lupus erythematosus: an updated meta-analysis and trial sequential analysis by Harishankar Mahto, Abhijit Pati, Sushil K Sahu, Hanuman Prasad Sharma, Archana Padhi and Aditya K Panda in Lupus

Supplemental material, sj-pdf-4-lup-10.1177_0961203320939156 for Association of MBL-2 gene polymorphisms with systemic lupus erythematosus: an updated meta-analysis and trial sequential analysis by Harishankar Mahto, Abhijit Pati, Sushil K Sahu, Hanuman Prasad Sharma, Archana Padhi and Aditya K Panda in Lupus

Supplemental material, sj-pdf-1-lup-10.1177_0961203320939156 for Association of MBL-2 gene polymorphisms with systemic lupus erythematosus: an updated meta-analysis and trial sequential analysis by Harishankar Mahto, Abhijit Pati, Sushil K Sahu, Hanuman Prasad Sharma, Archana Padhi and Aditya K Panda in Lupus

Supplemental material, sj-pdf-2-lup-10.1177_0961203320939156 for Association of MBL-2 gene polymorphisms with systemic lupus erythematosus: an updated meta-analysis and trial sequential analysis by Harishankar Mahto, Abhijit Pati, Sushil K Sahu, Hanuman Prasad Sharma, Archana Padhi and Aditya K Panda in Lupus

Supplemental material, sj-pdf-7-lup-10.1177_0961203320939156 for Association of MBL-2 gene polymorphisms with systemic lupus erythematosus: an updated meta-analysis and trial sequential analysis by Harishankar Mahto, Abhijit Pati, Sushil K Sahu, Hanuman Prasad Sharma, Archana Padhi and Aditya K Panda in Lupus

Supplemental material, sj-pdf-3-lup-10.1177_0961203320939156 for Association of MBL-2 gene polymorphisms with systemic lupus erythematosus: an updated meta-analysis and trial sequential analysis by Harishankar Mahto, Abhijit Pati, Sushil K Sahu, Hanuman Prasad Sharma, Archana Padhi and Aditya K Panda in Lupus

Supplemental material, sj-pdf-5-lup-10.1177_0961203320939156 for Association of MBL-2 gene polymorphisms with systemic lupus erythematosus: an updated meta-analysis and trial sequential analysis by Harishankar Mahto, Abhijit Pati, Sushil K Sahu, Hanuman Prasad Sharma, Archana Padhi and Aditya K Panda in Lupus