Biology subjects

Kanga, U.

Publications and source records attributed to Kanga, U..

3 recordsLinked to original sources

bioRxiv2026

Pathogen and host biomarkers to aid early diagnosis and prognosis of tuberculous meningitis

BackgroundTuberculous meningitis (TBM) is the most sinister form of extrapulmonary tuberculosis (EPTB), associated with high mortality due to delayed diagnosis and limited sensitivity of conventional and molecular tests. Current study evaluated the diagnostic utility of Lipoarabinomannan antigen (LAM) detection in CSF and urine and explored host inflammatory biomarkers for diagnosis and prognosis of TBM. MethodsThis prospective observational study enrolled 80 patients with presumptive TBM at a tertiary care centre. CSF samples were subjected to AFB microscopy, liquid culture(MGIT-960), GeneXpert MTB/RIF (GX), and LAM lateral flow assay. Urine LAM was performed at baseline. Serum and CSF levels of IL-1{beta}, IL-6, TNF-, IFN-{gamma}, IL-17A, and IP-10 were measured at baseline and after 1 month treatment. ResultsAmong 80 participants, 23 (28.7%) had definite TBM and 46 (57.5%) had probable TBM. CSF LAM sensitivity and specificity against microbiological reference standards was 43.5% and 80.7%, while urine LAM sensitivity (60.9%) and specificity 82.5% was higher. Against composite reference standards, both CSF and urine LAM showed reduced sensitivity but achieved 100% specificity. Serum IL-1{beta} showed the best diagnostic performance (AUC 0.943; sensitivity 88.9%, specificity 90.9%). Elevated serum and CSF IP-10 levels were associated with poor outcomes, whereas declining IL-6 and TNF- levels correlated with treatment response. ConclusionLAM detection in CSF and urine may serve as a highly specific, rapid rule-in test for TBM. Host inflammatory biomarkers, especially IL-1{beta} and IP-10, show additional diagnostic and prognostic value. Combining LAM testing with cytokine biomarkers may improve early diagnosis and efficient clinical management of TBM.

microbiology↗

bioRxiv2021

HLA-SPREAD: A comprehensive resource for HLA associated diseases, drug reactions and SNPs across populations

Extreme complexity in the Human Leukocyte Antigens (HLA) system and its nomenclature makes it difficult to interpret and integrate relevant information for HLA associations with diseases, Adverse Drug Reactions (ADR) and Transplantation. PubMed search displays [~]144,000 studies on HLA reported from multiple diseases in diverse locations. Currently, IPD-IMGT/HLA database houses data on 28,320 HLA alleles. We developed an automated pipeline with a unified graphical user interface HLA-SPREAD that provides a structured information on SNPs, Populations, REsources, ADRs and Diseases information. Information on HLA was extracted from [~]24 million PubMed abstracts extracted using Natural Language Processing (NLP). Python scripts were used to mine and curate information on diseases, filter false positives and categorize to 24 tree hierarchical groups and named Entity Recognition (NER) algorithms followed by semantic analysis to infer HLA association(s). This resource from 112 countries and 32 ethnic groups provides interesting insights on: markers associated with allelic/haplotypic association in autoimmune, cancer, viral and skin diseases, transplantation outcome and ADRs for hypersensitivity. Summary information on clinically relevant biomarkers related to HLA disease associations with mapped susceptible/risk alleles are readily retrievable from HLASPREAD. The resource is available at URL http://hla-spread.igib.res.in/. This resource is first of its kind that can help uncover novel patterns in HLA gene-disease associations.

bioinformatics↗

bioRxiv2018

Viral characteristics associated with sustenance of elite neutralizing activity in chronically HIV-1C infected monozygotic pediatric twins

Broad and potent neutralizing antibodies (bnAbs) with multiple epitope specificities evolve in HIV-1 infected children. Herein we studied two antiretroviral naive chronically HIV-1C in-fected monozygotic pediatric twins AIIMS_329 and AIIMS_330 with potent plasma bnAbs. Elite plasma neutralizing activity was observed since initial sampling at 78 months in AIIMS_330 and persisted throughout, while in AIIMS_329 it was seen at 90-months of age after which potency decreased overtime. We evaluated potential viral characteristics associated with the varied immune profile by generating single genome amplified pseudoviruses. The AIIMS_329 viruses generated from 90-month time point sampling were neutralization sensitive to second generation bnAbs and contemporaneous autologous plasma antibodies, while viruses from 112-months and 117-month timepoints were resistant to most bnAbs and autologous contemporaneous plasma. AIIMS_329 viruses developed resistance to plasma nAbs plausibly by N160-glycan loss, V1- and V4-loop lengthening. The viruses generated from AIIMS_330 at 90-month and 117-month timepoint showed varied susceptibility to bnAbs and autologous contemporaneous plasma antibodies while the viruses of 112-month timepoint, at which plasma nAb specificities mapped to the V2-glycan, V3-glycan and CD4bs, were resistant to autologous contemporaneous plasma antibodies as well as most bnAbs. We observed evolution of a viral pool in AIIMS_330 donor, comprising of plasma antibody neutralization sensitive or resistant diverse autologous viruses that in turn may have contributed to development and maintenance of elite neutralizing activity. The findings of this study provide information towards understanding factors involved in generation and maintenance of potent plasma nAbs.\n\nImportanceChronically HIV-1 infected children that develop elite neutralizing activity are suitable candidates to understand the mechanisms that lead to the co-evolution of virus and antibody response. Here, we evaluated the alterations in virus and antibody responses over time in chronically HIV-1C infected monozygotic pediatric twins, AIIMS_329 and AIIMS_330, who had acquired the infection by vertical transmission. AIIMS_330 retained the elite plasma neutralizing activity throughout, while in AIIMS_329, the potency decreased post 90 months of age. The corresponding viral pool from post 90-month samples in AIIMS_330 showed varied susceptibility, while that in AIIMS_329, developed resistance to bnAbs and autologous plasma antibodies. The findings of this study, conducted in twin children of same genetic make-up and infected at birth with a single source of HIV-1C, suggest that a viral pool with varied susceptibility to antibodies could have been one of the factors responsible for sustained elite neutralizing activity in AIIMS_330.

immunology↗