Publications by authors named "Ishita Marwah"

4 Publications

  • Page 1 of 1

Defining the Role of Cellular Immune Signatures in Diagnostic Evaluation of Suspected Tuberculosis.

J Infect Dis 2021 Jul 31. Epub 2021 Jul 31.

TB Research Centre, National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Background: Diagnosis of paucibacillary tuberculosis (TB) including extrapulmonary TB is a significant challenge, particularly in high-income, low-incidence settings. Measurement of Mycobacterium tuberculosis (Mtb)-specific cellular immune signatures by flow cytometry discriminates active TB from latent TB infection (LTBI) in case-control studies; however, their diagnostic accuracy and clinical utility in routine clinical practice is unknown.

Methods: Using a nested case-control study design within a prospective multicenter cohort of patients presenting with suspected TB in England, we assessed diagnostic accuracy of signatures in 134 patients who tested interferon-gamma release assay (IGRA)-positive and had final diagnoses of TB or non-TB diseases with coincident LTBI. Cellular signatures were measured using flow cytometry.

Results: All signatures performed less well than previously reported. Only signatures incorporating measurement of phenotypic markers on functional Mtb-specific CD4 T cells discriminated active TB from non-TB diseases with LTBI. The signatures measuring HLA-DR+IFNγ + CD4 T cells and CD45RA-CCR7-CD127- IFNγ -IL-2-TNFα + CD4 T cells performed best with 95% positive predictive value (95% confidence interval, 90-97) in the clinically challenging subpopulation of IGRA-positive but acid-fast bacillus (AFB) smear-negative TB suspects.

Conclusions: Two cellular immune signatures could improve and accelerate diagnosis in the challenging group of patients who are IGRA-positive, AFB smear-negative, and have paucibacillary TB.
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http://dx.doi.org/10.1093/infdis/jiab311DOI Listing
July 2021

Hypomorphic function and somatic reversion of DOCK8 cause combined immunodeficiency without hyper-IgE.

Clin Immunol 2016 Feb 8;163:17-21. Epub 2015 Dec 8.

Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, UK; Oxford NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.

Loss-of-function mutations in DOCK8 are linked to hyper-IgE syndrome. Patients typically present with recurrent sinopulmonary infections, severe cutaneous viral infections, food allergies and elevated serum IgE. Although patients may present with a spectrum of disease-related symptoms, molecular mechanisms explaining phenotypic variability in patients are poorly defined. Here we characterized a novel compound heterozygous mutation in DOCK8 in a patient diagnosed with primary combined immunodeficiency which was not typical of classical DOCK8 deficiency. In contrast to previously identified mutations in DOCK8 which result in complete loss of function, the newly identified single nucleotide insertion results in expression of a truncated DOCK8 protein. Functional evaluation of the truncated DOCK8 protein revealed its hypomorphic function. In addition we found somatic reversion of DOCK8 predominantly in T cells. The combination of somatic reversion and hypomorphic DOCK8 function explains the milder and atypical phenotype of the patient and further broadens the spectrum of DOCK8-associated disease.
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http://dx.doi.org/10.1016/j.clim.2015.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4758821PMC
February 2016

Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.

Clin Immunol 2015 Oct 26;160(2):301-14. Epub 2015 Jun 26.

Nuffield Department of Medicine, University of Oxford, Oxford, UK; Oxford NIHR Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK. Electronic address:

Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are highly variable and a genetic causes have been identified in <5% of patients. Here, we performed whole genome sequencing (WGS) of 34 CVID patients (94% sporadic) and combined them with transcriptomic profiling (RNA-sequencing of B cells) from three patients and three healthy controls. We identified variants in CVID disease genes TNFRSF13B, TNFRSF13C, LRBA and NLRP12 and enrichment of variants in known and novel disease pathways. The pathways identified include B-cell receptor signalling, non-homologous end-joining, regulation of apoptosis, T cell regulation and ICOS signalling. Our data confirm the polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together our data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways.
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http://dx.doi.org/10.1016/j.clim.2015.05.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4601528PMC
October 2015

Filaggrin-insufficiency in keratinocytes influences responsiveness of allergen-specific T cells to cognate antigen and compounds barrier function deficiency.

Clin Immunol 2014 Jul 29;153(1):153-5. Epub 2014 Apr 29.

MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. Electronic address:

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http://dx.doi.org/10.1016/j.clim.2014.04.011DOI Listing
July 2014
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