Characteristic TLRs expression profile associated with distinct autoantibody repertoire is suggestive of differential immuno-regulatory pathways operative in different subsets of SLE patients.

Systemic lupus erythematosus (SLE) patients exhibit immense heterogeneity which is challenging from the diagnostic perspective. Emerging high throughput sequencing technologies have been proved to be a useful platform to understand the complex and dynamic disease processes. SLE patients categorised based on autoantibody specificities are reported to have differential immuno-regulatory mechanisms. Therefore, we performed RNA-seq analysis to identify transcriptomics of SLE patients with distinguished autoantibody specificities. The SLE patients were segregated into three subsets based on the type of autoantibodies present in their sera (anti-dsDNA+ group with anti-dsDNA autoantibody alone; anti-ENA+ group having autoantibodies against extractable nuclear antigens (ENA) only, and anti-dsDNA+ENA+ group having autoantibodies to both dsDNA and ENA). Global transcriptome profiling for each SLE patients subsets was performed using Illumina® Hiseq-2000 platform. The biological relevance of dysregulated transcripts in each SLE subsets was assessed by ingenuity pathway analysis (IPA) software. We observed that dysregulation in the transcriptome expression pattern was clearly distinct in each SLE patients subsets. IPA analysis of transcripts uniquely expressed in different SLE groups revealed specific biological pathways to be affected in each SLE subsets. Multiple cytokine signaling pathways were specifically dysregulated in anti-dsDNA+ patients whereas Interferon signaling was predominantly dysregulated in anti-ENA+ patients. In anti-dsDNA+ENA+ patients regulation of actin based motility by Rho pathway was significantly affected. The granulocyte gene signature was a common feature to all SLE subsets; however, anti-dsDNA+ group showed relatively predominant expression of these genes. Dysregulation of Plasma cell related transcripts were higher in anti-dsDNA+ and anti-ENA+ patients as compared to anti-dsDNA+ ENA+. Association of specific canonical pathways with the uniquely expressed transcripts in each SLE subgroup indicates that specific immunological disease mechanisms are operative in distinct SLE patients’ subsets. This ‘sub-grouping’ approach could further be useful for clinical evaluation of SLE patients and devising targeted therapeutics.

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The differential miRNA expression in patients with distinct autoantibodies is suggestive of different regulatory mechanisms operating among them. Based on these observations, we are hopeful that this 'sub-grouping' approach could be used to identify other defective processes associated with varying disease manifestations in SLE and may be considered when designing therapeutic interventions.

This study examines the annual, seasonal and diurnal variations in the ambient concentrations of ozone at a suburban site of Varanasi, India, during 2002. Prominent seasonal variations in ozone concentrations were recorded. Ozone concentrations were higher during the warmer months. Daytime 12-hourly mean monthly ozone concentrations varied from 45.18 to 62.35 ppb during summer, from 28.55 to 44.25 ppb during winter and from 24 to 43.85 ppb during the rainy season from 2002 to 2006. Distinct diurnal variations in ozone concentrations were also observed. Daytime maxima in ozone concentration were recorded between 1200 and 1400 h, whereas morning and evening hours showed lower concentrations of ozone. Ozone concentrations in the atmosphere depended on several meteorological factors. Monthly average ozone concentration was significantly correlated with maximum temperature (p,0.001) and mean monthly temperature (p,0.05), maximum relative humidity (p,0.001), minimum relative humidity (p,0.001) and mean monthly relative humidity (p,0.001), and sunshine hours (p,0.001). Ozone concentrations in the ambient air have shown an increase in the past decade that was more in the winter and rainy seasons than in the summer. This study suggests that ozone concentrations around Varanasi were sufficiently high to cause significant damage to agricultural production. The present work can be extended to a regional level by incorporating modelling studies using recent remote sensing tools.

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