Susceptibility to Mycobacterium tuberculosis Infection in HIV-Positive Patients Is Associated With CARD8 Genetic Variant

Pontillo, Alessandra; Carvalho, Márcia Schneider de Mendonça Gomes de Zuzarte; Kamada, Anselmo Jiro; Moura, Ronald; Schindler, Haiana Charifker; Duarte, Alberto J. S.; Crovella, Sérgio

doi:10.1097/qai.0b013e31828f93bb

Cited by 40 publications

(34 citation statements)

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“…Renewed global interest led to advances in recognising TB/HIV co-infection and understanding the mechanisms promoting susceptibility of HIV-infected people in developing TB disease as part of a multifactorial process [26-30]. Diagnosis of HIV/TB co-infection in children is still challenging.…”

Section: Resultsmentioning

confidence: 99%

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Tuberculosis and HIV co-infection in children

et al. 2014

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HIV is the top and tuberculosis is the second leading cause of death from infectious disease worldwide, with an estimated 8.7 million incident cases of tuberculosis and 2.5 million new HIV infections annually. The World Health Organization estimates that HIV prevalence among children with tuberculosis, in countries with moderate to high prevalence, ranges from 10 to 60%. The mechanisms promoting susceptibility of people with HIV to tuberculosis disease are incompletely understood, being likely caused by multifactorial processes.Paediatric tuberculosis and HIV have overlapping clinical manifestations, which could lead to missed or late diagnosis. Although every effort should be made to obtain a microbiologically-confirmed diagnosis in children with tuberculosis, in reality this may only be achieved in a minority, reflecting their paucibacillary nature and the difficulties in obtain samples. Rapid polymerase chain reaction tests, such as Xpert MTB/RIF assay, are increasingly used in children. The use of less or non invasive methods of sample collection, such as naso-pharyngeal aspirates and stool samples for a polymerase chain reaction-based diagnostic test tests and mycobacterial cultures is promising technique in HIV negative and HIV positive children. Anti-tuberculosis treatment should be started immediately at diagnosis with a four drug regimen, irrespective of the disease severity. Moreover, tuberculosis disease in an HIV infected child is considered to be a clinical indication for initiation of antiretroviral treatment. The World Health Organization recommends starting antiretroviral treatment in children as soon as anti-tuberculosis treatment is tolerated and within 2- 8 weeks after initiating it. The treatment of choice depends on the child’s age and availability of age-appropriate formulations, and potential drug interactions and resistance. Treatment of multi-drug resistant tuberculosis in HIV-infected children follows same principles as for HIV uninfected children. There are conflicting results on effectiveness of isoniazid preventive therapy in reducing incidence of tuberculosis disease in children with HIV.ConclusionData on HIV/TB co-infection in children are still lacking. There are on-going large clinical trials on the prevention and treatment of TB/HIV infection in children that hopefully will help to guide an evidence-based clinical practice in both resource-rich and resource-limited settings.

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Section: Resultsmentioning

confidence: 99%

“…A recent case-control study in Brazil showed the novel association between certain inflammasome gene polymorphisms (i.e. CARD8 genetic variants) and the development of TB infection in HIV positive subjects [30]. …”

Section: Impact Of Hiv On Pathogenesis Of Tbmentioning

confidence: 99%

Tuberculosis and HIV co-infection in children

et al. 2014

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“…DNA (Hirako et al, 2015) or phospholipid-specific Abs can activate the inflammasome in monocytes (Muller-Calleja et al, 2015; Prinz et al, 2011). Moreover, in some TB studies, inflammasome activation has been linked to bacterial control (Carlsson et al, 2010; Eklund et al, 2014; Mishra et al, 2010; Pontillo et al, 2013). Thus, our data suggest that Abs could direct inflammasome activation in macrophages, and this may contribute to bacterial control.…”

Section: Discussionmentioning

confidence: 99%

A Functional Role for Antibodies in Tuberculosis

Chung

Rosebrock

et al. 2016

Cell

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Summary While a third of the world carries the burden of tuberculosis, disease control has been hindered by the lack of tools including a rapid, point-of-care diagnostic and a protective vaccine. In many infectious diseases, antibodies (Abs) are powerful biomarkers and important immune mediators. However, in Mycobacterium tuberculosis (Mtb) infection, a discriminatory or protective role for humoral immunity remains unclear. Using an unbiased antibody profiling approach we show that individuals with latent tuberculosis infection (Ltb) and active tuberculosis disease (Atb) have distinct Mtb-specific humoral responses, such that Ltb infection is associated with unique Ab Fc functional profiles, selective binding to FcγRIII, and distinct Ab glycosylation patterns. Moreover, compared to Abs from Atb, Abs from Ltb drove enhanced phagolysosomal maturation, inflammasome activation, and most importantly, macrophage killing of intracellular Mtb. Combined, these data point to a potential role for Fc-mediated Ab effector functions, tuned via differential glycosylation, in Mtb control.

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“…For example, using a genomewide screening approach in M. tuberculosis-infected vs. noninfected dendritic cells, Barreiro et al (2012) found a number of expression quantitative trait loci that associate with tuberculosis in this system, and imputation of 1000 Genomes Project data (1000Genomes Project Consortium et al, 2012 into a Ghanaian genomewide data set (tuberculosis cases and healthy controls) revealed a resistance locus at 11p13 downstream of WT1 (Thye et al, 2012). Recently, susceptibility to tuberculosis in HIV-1-infected individuals was associated with a CARD8 genetic variant (Pontillo et al, 2013), and a genotype resulting in high IL-10 production also appeared to predispose HIV-1-infected individuals to TB infection (Ramaseri Sunder et al, 2012). Recently, susceptibility to tuberculosis in HIV-1-infected individuals was associated with a CARD8 genetic variant (Pontillo et al, 2013), and a genotype resulting in high IL-10 production also appeared to predispose HIV-1-infected individuals to TB infection (Ramaseri Sunder et al, 2012).…”

Section: The Role Of Host Genetic Variationmentioning

confidence: 99%

Co-infection withMycobacterium tuberculosisand human immunodeficiency virus: an overview and motivation for systems approaches

2013

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Tuberculosis is a devastating disease that accounts for a high proportion of infectious disease morbidity and mortality worldwide. HIV-1 co-infection exacerbates tuberculosis. Enhanced understanding of the host-pathogen relationship in HIV-1 and Mycobacterium tuberculosis co-infection is required. While reductionist approaches have yielded many valuable insights into disease pathogenesis, systems approaches are required that develop data-driven models able to predict emergent properties of this complex co-infection system in order to develop novel therapeutic approaches and to improve diagnostics. Here, we provide a pathogenesis-focused overview of HIV-TB co-infection followed by an introduction to systems approaches and concrete examples of how such approaches are useful.

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Susceptibility to Mycobacterium tuberculosis Infection in HIV-Positive Patients Is Associated With CARD8 Genetic Variant

Cited by 40 publications

References 28 publications

Tuberculosis and HIV co-infection in children

Tuberculosis and HIV co-infection in children

A Functional Role for Antibodies in Tuberculosis

Co-infection withMycobacterium tuberculosisand human immunodeficiency virus: an overview and motivation for systems approaches

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