Athavale, A. | Search bioRxiv

bioRxiv2025

Antibody Responses to Salmonella Typhi Antigens among Typhoid Recovered Individuals in an Endemic Region

BackgroundTyphoid fever remains a major public health concern in endemic regions, yet the nature of antibody responses to individual Salmonella Typhi antigens and their potential role in modulating cellular immune functions are not well understood. This gap also applies to the long-term immune response after the vaccination against the disease. ObjectivesTo evaluate the humoral and cellular immune response against the Salmonella Typhi antigens among the Typhoid recovered individuals. MethodsELISA was used to measure antibody responses against five S. Typhi antigens in plasma samples from typhoid-recovered individuals and healthy participants. Vi polysaccharide-specific plasma antibodies were tested for their ability to activate NK cells isolated from healthy donors. Flow cytometry-based assays were performed to analyze T cell and B cell profiles in the peripheral circulation of these individuals. ResultsPolysaccharide antigens mounted better IgA responses among typhoid-recovered individuals compared with healthy participants. Anti-S. Typhi IgM was significantly elevated in the typhoid group for all five antigens (p<0.05), while no significant differences were observed in IgG responses. NK cell activation assays showed comparable levels of activation markers of the NK cells isolated from healthy individuals and treated with the plasma of Typhoid recovered individuals. Analysis of B cell subsets revealed largely comparable distributions between the two groups; however, transitional B cells were elevated among the Typhoid recovered individuals. HlyE-specific memory B cells were detectable in both the groups. CD4 T cell subsets were similar between typhoid-recovered and healthy individuals, whereas differences were observed in CD8 T cell populations, with higher TEMRA cells among recovered individuals and relatively higher central memory CD8 T cells in healthy participants. ConclusionPolysaccharide antigens elicited significantly better IgA response in recovered typhoid participants, possibly reflecting mucosal immune priming from the gut. Persistent IgM antibodies after recovery suggest durable IgM responses following typhoid infection. Similar IgG levels between groups and the presence of antigen-specific memory cells in healthy individuals highlight the influence of repeated exposure in endemic settings. Elevated transitional B cells suggest the reinforcement of the B cells to the peripheral circulation during the disease which remained in the circulation of these individuals. However, elevated TEMRA population of the CD8 T cells has been observed in several other infectious diseases including this study. These findings demonstrate the complexity of humoral and cellular immune responses to S. Typhi in endemic regions.

immunology↗

bioRxiv2018

Redefining Nephrotic Syndrome in Molecular Terms: Outcome-associated molecular clusters and patient stratification with noninvasive surrogate biomarkers

A tissue transcriptome driven classification of nephrotic syndrome patients identified a high risk group of patients with TNF activation and established a non-invasive marker panel for pathway activity assessment paving the way towards precision medicine trials in NS.\n\nAbstractNephrotic syndrome from primary glomerular diseases can lead to chronic kidney disease (CKD) and/or end-stage renal disease (ESRD). Conventional diagnoses using a combination of clinical presentation and descriptive biopsy information do not accurately predict risk for progression in patients with nephrotic syndrome, which complicates disease management. To address this challenge, a transcriptome-driven approach was used to classify patients with minimal change disease and focal segmental glomerulosclerosis in the Nephrotic Syndrome Study Network (NEPTUNE). Transcriptome-based classification revealed a group of patients at risk for disease progression. High risk patients had a transcriptome profile consistent with TNF activation. Non-invasive urine biomarkers TIMP1 and CCL2 (MCP1), which are causally downstream of TNF, accurately predicted TNF activation in the NEPTUNE cohort setting the stage for patient stratification approaches and precision medicine in kidney disease.

systems biology↗