Mycobacterium tuberculosis-specific plasmablast levels are differentially modulated in tuberculosis infection and disease

Awa Gindeh,Olumuyiwa Owolabi,Simon Donkor,Jayne S Sutherland

doi:10.1016/j.tube.2020.101978

Awa Gindeh, Olumuyiwa Owolabi + Show 2 more

Open Access

https://doi.org/10.1016/j.tube.2020.101978

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Journal: Tuberculosis	Publication Date: Aug 1, 2020
Citations: 5	License type: cc-by

Affiliation: MRC Unit the Gambia

Abstract

BackgroundWhile T cell responses to Mycobacterium tuberculosis (Mtb) have been extensively studied, the role of B-cells and antibodies are less well characterised. The aim of this study was to assess levels of Mtb-specific IgG + plasmablasts across the Mtb infection spectrum. MethodsPatients with active TB were analysed at baseline and 6 months of therapy (n = 20).Their exposed household contacts (HHC) included individuals with latent TB infection (LTBI; n = 20); evident at baseline; individuals with a negative Tuberculin Skin Test (TST) at baseline who became; positive at 6 months (converters; n = 11) and those who remained negative (non-converters; n = 10). An e x-vivo B-cell ELISPOT was performed to analyse plasmablast responses. ResultsFrequencies of ESAT-6/CFP-10 (EC)- but not Whole Cell Lysate (WCL)-specific plasmablasts were significantly higher in patients with active TB pre-treatment compared to post-treatment (p = 0.002) and compared to HHC with LTBI (p < 0.0001). Conversely, total IgG + plasmablasts were significantly decreased in TB patients at baseline. No difference was seen in levels of plasmablasts between TST converters and non-converters at baseline. ConclusionsWe show that EC-specific plasmablast levels are differentially modulated during TB infection and disease, with levels highest during active TB. These data provide new insights into TB biomarker development and avenues for novel immune interventions.

Highlights

Despite the availability of a vaccine and an effective anti-TB therapy, TB still remains a major global health problem [1]
Plasmablast levels in active TB disease compared to latent TB infection (LTBI)
In this study we have shown that peripheral Mycobacterium tuberculosis (Mtb)-specific plasmablast responses are differentially modulated at key control points within the Mtb infection spectrum

Summary

Introduction

Despite the availability of a vaccine and an effective anti-TB therapy, TB still remains a major global health problem [1]. The predominant contributing factors to the sustained epidemic are lack of a protective vaccine, HIV infection, diagnostic difficulties and emergence of multi and extensive drug resistant strains of Mycobacterium tuberculosis (Mtb) [2]. This resulted in 10 million newly diagnosed cases and 1.5 million deaths in HIV negative individuals in 2018 [3]. Conclusions: We show that EC-specific plasmablast levels are differentially modulated during TB infection and disease, with levels highest during active TB These data provide new insights into TB biomarker development and avenues for novel immune interventions

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Results

Conclusion