Associations Between Human Leukocyte Antigen Class I Variants and the Mycobacterium tuberculosis Subtypes Causing Disease

Salie, Muneeb; Merwe, Lize van der; Möller, Marlo; Daya, Michelle; Spuy, Gian D. van der; Helden, Paul D. van; Martin, Maureen P.; Gao, Xiaojiang; Warren, Robin M.; Carrington, Mary; Hoal, Eileen G.

doi:10.1093/infdis/jit443

Cited by 59 publications

(49 citation statements)

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“…Of the 8 SNPs, 2 HLA class-I intergenic SNPs (rs2394885 and rs2922997) were shown to capture the associations, with rs2394885 tagging the HLA-C*15:05 allele in the Vietnamese population. We have also previously shown that HLA class-I variants are associated with disease caused by specific M. tuberculosis subtypes [15].…”

Section: Discussionmentioning

confidence: 80%

“…Several associations with TB susceptibility have been noted across different ethnic populations, with different alleles identified in each population. This finding may not be that surprising given that HLAs are known to be population-specific, with different environments selecting for different alleles [15]. The data therefore suggests great variability in the HLA alleles involved in TB susceptibility in different populations.…”

Section: Discussionmentioning

confidence: 88%

“…Correction for multiple testing was not done, as the methods that are currently available to address this issue, e.g. the Bonferroni correction and Bayesian modeling, are not appropriate for the data being investigated [15]. All analyses were done in R (freely available from www.r-project.org) using functions from base R and the R genetics package.…”

Section: Discussionmentioning

confidence: 99%

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Activating KIRs alter susceptibility to pulmonary tuberculosis in a South African population

et al. 2015

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confidence: 80%

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confidence: 88%

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confidence: 99%

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Activating KIRs alter susceptibility to pulmonary tuberculosis in a South African population

et al. 2015

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“…tuberculosis isolates found in epidemiologically defined clusters are defined as successful because they transmit and cause TB in more human hosts, in the same population, than the case for other isolates. It is also a generally accepted idea that overall strain success depends on a combination of strain virulence traits and host genetic factors (8,14,16,62,63). The contribution of mycobacterial VFs to establishing disease (TB) or causing pathogenicity, however, was recently reemphasized (42,64); as VFs are likely to be lineage specific (23-25, 38, 43), their existence might have far-reaching impacts on the efficacy of new TB vaccines or drugs (65).…”

Section: Discussionmentioning

confidence: 99%

Correlates between Models of Virulence for Mycobacterium tuberculosis among Isolates of the Central Asian Lineage: a Case for Lysozyme Resistance Testing?

et al. 2015

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e Virulence factors (VFs) contribute to the emergence of new human Mycobacterium tuberculosis strains, are lineage dependent, and are relevant to the development of M. tuberculosis drugs/vaccines. VFs were sought within M. tuberculosis lineage 3, which has the Central Asian (CAS) spoligotype. Three isolates were selected from clusters previously identified as dominant in London, United Kingdom. Strain-associated virulence was studied in guinea pig, monocyte-derived macrophage, and lysozyme resistance assays. Whole-genome sequencing, single nucleotide polymorphism (SNP) analysis, and a literature review contributed to the identification of SNPs of interest. The animal model revealed borderline differences in strain-associated pathogenicity. Ex vivo, isolate C72 exhibited statistically significant differences in intracellular growth relative to C6 and C14. SNP candidates inducing lower fitness levels included 123 unique nonsynonymous SNPs, including three located in genes (lysX, caeA, and ponA2) previously identified as VFs in the laboratory-adapted reference strain H37Rv and shown to confer lysozyme resistance. C72 growth was most affected by lysozyme in vitro. A BLAST search revealed that all three SNPs of interest (C35F, P76Q, and P780R) also occurred in Tiruvallur, India, and in Uganda. Unlike C72, however, no single isolate identified through BLAST carried all three SNPs simultaneously. CAS isolates representative of three medium-sized human clusters demonstrated differential outcomes in models commonly used to estimate strain-associated virulence, supporting the idea that virulence varies within, not just across, M. tuberculosis lineages. Three VF SNPs of interest were identified in two additional locations worldwide, which suggested independent selection and supported a role for these SNPs in virulence. The relevance of lysozyme resistance to strain virulence remains to be established. Human and animal tuberculosis (TB) is caused by a group of closely related bacteria (Mycobacterium tuberculosis, M. canettii, M. africanum, M. microti, M. bovis, M. caprae, M. pinnipedii, M. mungi, and M. orygis) collectively referred to as the Mycobacterium tuberculosis complex (MTBC) (1-6). M. tuberculosis is the main agent of TB in humans. Within M. tuberculosis itself, single nucleotide polymorphisms (SNPs) and large sequence polymorphisms (LSPs) are used to further classify M. tuberculosis into four (sensu stricto) major lineages, each of which is found to strongly associate with specific geographic human populations (7). While strong lineage associations with specific human populations or regions of the world are well acknowledged (8-12), the causes and relevance of this to bacterial virulence and clinical presentation are still only partly understood (13-16). It has become clear, however, that the previously unrecognized genetic diversity among M. tuberculosis isolates has an impact on the outcome of infection (17-19), and different approaches have been undertaken towards a better understanding of what makes a strain...

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“…Diese enge Beziehung überdauert selbst eine Vermischung verschiedener ethnischer Gruppen in kosmopolitischen Städten wie San Francisco und Montreal [7]. In diesem Zusammenhang hat eine aktuelle Studie aus Südafrika eine Assoziation von bestimmten HLA-Genotypen mit Infektionen durch die MTB-Stäm-me Beijing, LAM, LCC und Quebec gezeigt [8]. Die HIV-Infektion kann jedoch diese stabile Beziehung zwischen dem Wirt und dem Erreger zerstören [9].…”

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Aktuelle Aspekte zur Epidemiologie, Diagnose und Therapie der Tuberkulose bei HIV-infizierten Patienten

Saleeb

Buchwald

2014

Pneumologie

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Globally, the diagnosis and treatment of tuberculosis (TB) in HIV-co-infection has improved dramatically over the last 10 years. Nonetheless, the mortality of co-infected patients remains elevated. In European countries, the proportion of HIV-infected patients amongst all TB cases varies greatly; in Germany it is about 4 - 5%. HIV-infection changes the molecular epidemiology of TB and the drug resistance situation. In endemic areas, HIV-infected patients are often re-infected after completion of treatment for active TB. HIV has a profound influence on the anti-TB-immune response and antiretroviral therapy (ART) cannot completely restore normal immune function. The clinical presentation in advanced HIV-infection is atypical and disseminated disease is common. New "Point-of-Care" test methods are poised to improve the diagnoses of TB in HIV-infection; however, further research is required. The treatment of co-infection is complicated by drug interactions and the immune reconstitution syndrome (IRIS). New concepts and treatment regimens for chemoprevention of TB are necessary, especially for HIV-infected persons.

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Associations Between Human Leukocyte Antigen Class I Variants and the Mycobacterium tuberculosis Subtypes Causing Disease

Abstract: This is the first report of the association of human HLA types and M. tuberculosis strain genotype, highlighting that both host and pathogen genetics need to be taken into consideration when studying tuberculosis disease development.

Cited by 59 publications

References 45 publications

Activating KIRs alter susceptibility to pulmonary tuberculosis in a South African population

Activating KIRs alter susceptibility to pulmonary tuberculosis in a South African population

Correlates between Models of Virulence for Mycobacterium tuberculosis among Isolates of the Central Asian Lineage: a Case for Lysozyme Resistance Testing?

Aktuelle Aspekte zur Epidemiologie, Diagnose und Therapie der Tuberkulose bei HIV-infizierten Patienten

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