Antibody Subclass and Glycosylation Shift Following Effective TB Treatment

Grace, Patricia S.; Dolatshahi, Sepideh; Lu, Lenette L.; Cain, Adam; Palmieri, Fabrizio; Petrone, Linda; Fortune, Sarah M.; Ottenhoff, Tom H. M.; Lauffenburger, Douglas A.; Goletti, Delia; Joosten, Simone A.; Alter, Galit

doi:10.3389/fimmu.2021.679973

Cited by 33 publications

(42 citation statements)

References 78 publications

(116 reference statements)

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“…In the treated group, PPD-specific phagocytosis, and increased HspX-IgG and Ag85-IgM were seen in the txATB subjects. In the ATB group, expanded IgA titers to Ag85A/B whereas higher PPD-IgM and HspX-IgG1 were significantly higher in the txATB cohort, which may be indicative of effector functions used to control infection ( 317 ).…”

Section: Cell Subsets Widening the Viewmentioning

confidence: 99%

“…Different TB-specific antibody subclasses and glycosylation patterns have been characterized, offering interesting perspectives on how a reduction in a humoral marker of TB disease (IgG4) can potentially track the success of drug treatment ( 317 ). Grace et al.…”

Section: Cell Subsets Widening the Viewmentioning

confidence: 99%

“…Grace et al. have recently reported striking differences in the TB-specific antibodies in four human cohorts in different stages of TB: healthy, latent TB infection (LTBI), active TB (ATB), and treated active TB (txATB) ( 317 ). ATB subjects were enrolled within 1 week of treatment with isoniazid, rifampicin, ethambutol, and pyrazinamide for 2 months followed by 4 months of isoniazid and rifampicin.…”

Section: Cell Subsets Widening the Viewmentioning

confidence: 99%

“…LTBI patients were contacts of patients with ATB, with positive QuantiFERON-TB Gold results but no symptoms of TB. Antibody profiling included responses to several TB antigens including PPD, recombinant Ag85A/B (1:1 ratio), ESAT6/CFP10 (1:1 ratio), GroES, glcB, and HspX ( 317 ). Of note, enrichment of PPD-specific IgG4 was shown in the ATB cohort, and depleting this specific subclass led to increases in neutrophil and NK effector functions.…”

Section: Cell Subsets Widening the Viewmentioning

confidence: 99%

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It Takes a Village: The Multifaceted Immune Response to Mycobacterium tuberculosis Infection and Vaccine-Induced Immunity

Larsen

Williams²,

Rais³

et al. 2022

Front. Immunol.

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Despite co-evolving with humans for centuries and being intensely studied for decades, the immune correlates of protection against Mycobacterium tuberculosis (Mtb) have yet to be fully defined. This lapse in understanding is a major lag in the pipeline for evaluating and advancing efficacious vaccine candidates. While CD4+ T helper 1 (TH1) pro-inflammatory responses have a significant role in controlling Mtb infection, the historically narrow focus on this cell population may have eclipsed the characterization of other requisite arms of the immune system. Over the last decade, the tuberculosis (TB) research community has intentionally and intensely increased the breadth of investigation of other immune players. Here, we review mechanistic preclinical studies as well as clinical anecdotes that suggest the degree to which different cell types, such as NK cells, CD8+ T cells, γ δ T cells, and B cells, influence infection or disease prevention. Additionally, we categorically outline the observed role each major cell type plays in vaccine-induced immunity, including Mycobacterium bovis bacillus Calmette-Guérin (BCG). Novel vaccine candidates advancing through either the preclinical or clinical pipeline leverage different platforms (e.g., protein + adjuvant, vector-based, nucleic acid-based) to purposefully elicit complex immune responses, and we review those design rationales and results to date. The better we as a community understand the essential composition, magnitude, timing, and trafficking of immune responses against Mtb, the closer we are to reducing the severe disease burden and toll on human health inflicted by TB globally.

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Section: Cell Subsets Widening the Viewmentioning

confidence: 99%

Section: Cell Subsets Widening the Viewmentioning

confidence: 99%

Section: Cell Subsets Widening the Viewmentioning

confidence: 99%

Section: Cell Subsets Widening the Viewmentioning

confidence: 99%

See 2 more Smart Citations

It Takes a Village: The Multifaceted Immune Response to Mycobacterium tuberculosis Infection and Vaccine-Induced Immunity

Larsen

Williams²,

Rais³

et al. 2022

Front. Immunol.

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“…However, more recent studies showed promising results for antibody signatures [ 81 , 82 ]. Recently, TB-specific IgG4 has been shown to correlate with disease activity and decrease after treatment [ 83 ].…”

Section: Pipeline and Developments Of Point-of-care Tests For The Dia...mentioning

confidence: 99%

Towards Accurate Point-of-Care Tests for Tuberculosis in Children

et al. 2022

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In childhood tuberculosis (TB), with an estimated 69% of missed cases in children under 5 years of age, the case detection gap is larger than in other age groups, mainly due to its paucibacillary nature and children’s difficulties in delivering sputum specimens. Accurate and accessible point-of-care tests (POCTs) are needed to detect TB disease in children and, in turn, reduce TB-related morbidity and mortality in this vulnerable population. In recent years, several POCTs for TB have been developed. These include new tools to improve the detection of TB in respiratory and gastric samples, such as molecular detection of Mycobacterium tuberculosis using loop-mediated isothermal amplification (LAMP) and portable polymerase chain reaction (PCR)-based GeneXpert. In addition, the urine-based detection of lipoarabinomannan (LAM), as well as imaging modalities through point-of-care ultrasonography (POCUS), are currently the POCTs in use. Further to this, artificial intelligence-based interpretation of ultrasound imaging and radiography is now integrated into computer-aided detection products. In the future, portable radiography may become more widely available, and robotics-supported ultrasound imaging is currently being trialed. Finally, novel blood-based tests evaluating the immune response using “omic-“techniques are underway. This approach, including transcriptomics, metabolomic, proteomics, lipidomics and genomics, is still distant from being translated into POCT formats, but the digital development may rapidly enhance innovation in this field. Despite these significant advances, TB-POCT development and implementation remains challenged by the lack of standard ways to access non-sputum-based samples, the need to differentiate TB infection from disease and to gain acceptance for novel testing strategies specific to the conditions and settings of use.

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