APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis

Cooper, Anneli; Ilboudo, Hamidou; Alibu, Vincent P.; Ravel, Sophie; Enyaru, John; Weir, William; Noyes, Harry; Capewell, Paul; Camara, Mamadou; Milet, Jacqueline; Jamonneau, Vincent; Camara, Oumou; Matovu, Enock; Bucheton, Bruno; MacLeod, Annette

doi:10.7554/elife.25461

Cited by 109 publications

(130 citation statements)

References 64 publications

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“…Since the launch of the TrypanoGen network, studies highlighting or confirming the association between different SNPs in a number of genes (HP, IL6, APOL1) and the individual variability in susceptibility to the development of HAT have been published. These results further prove the importance of the genetic component in the susceptibility to sleeping sickness in the human host …”

Section: Genomics To Study Susceptibility To Hatsupporting

confidence: 59%

Sleeping Sickness in the ‘Omics Era

Tiberti

Sanchez

2018

Proteomics Clinical Apps

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Sleeping sickness is a neglected tropical disease caused by Trypanosoma brucei parasites, affecting the poorest communities in sub-Saharan Africa. The great efforts done by the scientific community, local governments, and non-governmental organizations (NGOs) via active patients' screening, vector control, and introduction of improved treatment regimens have significantly contributed to the reduction of human African trypanosomiasis (HAT) incidence during the last 15 years. Consequently, the WHO has announced the objective of HAT elimination as a public health problem by 2020. Studies at both parasite and host levels have improved our understanding of the parasite biology and the mechanisms of parasite interaction with its mammalian host. In this review, the impact that 'omics studies have had on sleeping sickness by revealing novel properties of parasite's subcellular organelles are summarized, by highlighting changes induced in the host during the infection and by proposing potential disease markers and therapeutic targets.

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Section: Genomics To Study Susceptibility To Hatsupporting

confidence: 59%

Sleeping Sickness in the ‘Omics Era

Tiberti

Sanchez

2018

Proteomics Clinical Apps

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“…Interestingly, no association was found with genes encoding proteins known to be involved in the human infectivity of African trypanosomes (APOL1, HPR (Vanhollebeke et al 2008;Vanhamme et al 2003)). Indeed, APOL1 alleles have previously been found to associate with the development of a latent phenotype in this population (Cooper et al 2017). This discrepancy may a result of using a population comprised of immune cells that do not express these proteins or simply due to population size.…”

Section: Discussionmentioning

confidence: 82%

“…In contrast high levels of immunosuppressive molecules, such as IL-10 and the maternal human leukocyte antigen protein HLA-G, were predictive of disease development in serological positive suspects (Ilboudo et al 2014;Gineau et al 2016). Contrasting associations have also been reported with APOL1 alleles that predispose patients to renal disease (Cooper et al 2017). The APOL1 G1 allele was found at higher frequencies in latent infections, while the G2 allele associated with an increased risk of HAT.…”

Section: Introductionmentioning

confidence: 99%

T cell activation and the HLA locus associate with latent infections of human African trypanosomiasis

Capewell

Bucheton²,

Clucas

et al. 2017

Preprint

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Infections by many pathogens can result in a wide range of phenotypes, from severe to mild, or even asymptomatic. Understanding the genetic basis of these phenotypes can lead to better tools to treat patients or detect reservoirs. To identify human genetic factors that contribute to symptoms diversity, we examined the range of disease severities caused by the parasite T. b. gambiense, the primary cause of human African trypanosomiasis (HAT). We analyzed the transcriptomes of immune cells from both symptomatic HAT cases and individuals with latent infections. Our analysis identified several genes and pathways that associated with the latent phenotype, primarily suggesting increased T and B cell activation in HAT patients relative to latent infections.We also used these transcriptome data to conduct an exome-wide single nucleotide polymorphism (SNP) association study. This suggested that SNPs in the human major histocompatibility locus (HLA) associate with severity, supporting the transcription data and suggesting that T cell activation is a determining factor in outcome. Finally, to establish if T cell activation controls disease severity, we blocked co-stimulatory dependent T cell activation in an animal model for HAT. This showed that reducing T cell activation during trypanosome infection improves symptoms and reduces parasitemia. Our data has used a combination of transcriptome-wide analysis and an in vivo model to reveal that T cell activation and the HLA locus associate with the development of symptoms during HAT. This may open new avenues for the development of new therapeutics and prognostics.

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“…al. 2013;Genovese et al 2010;Cooper et al 2017;Courtin et al 2013; 351! (Supplementary figure S10, Supplementary table S5…”

Section: !mentioning

confidence: 99%

Evidence of population specific selection inferred from 289 genome sequences of Nilo-Saharan and Niger-Congo linguistic groups in Africa

Mulindwa

Noyes

Ilboudo

et al. 2017

Preprint

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APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis

Cited by 109 publications

References 64 publications

Sleeping Sickness in the ‘Omics Era

Sleeping Sickness in the ‘Omics Era

T cell activation and the HLA locus associate with latent infections of human African trypanosomiasis

Evidence of population specific selection inferred from 289 genome sequences of Nilo-Saharan and Niger-Congo linguistic groups in Africa

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