Dataset Information

Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians.

ABSTRACT: Indigenous populations, including Indigenous Australians, are highly susceptible to severe influenza disease and the underlying mechanisms are unknown. We studied immune and genetic factors that could predicate severe influenza disease in Indigenous Australians enrolled in the LIFT study: looking into influenza T-cell immunity. To examine CD8(+) T-cell immunity, we characterised human leukocyte antigen (HLA) profiles. HLA typing confirmed previous studies showing predominant usage of HLA-A*02:01, 11:01, 24:02, 34:01 and HLA-B*13:01, 15:21, 40:01/02, 56:01/02 in Indigenous Australians. We identified two new HLA alleles (HLA-A*02:new and HLA-B*56:new). Modelling suggests that variations within HLA-A*02:new (but not HLA-B56:new) could affect peptide binding. There is a relative lack of known influenza epitopes for the majority of these HLAs, with the exception of a universal HLA-A*02:01-M158 epitope and proposed epitopes presented by HLA-A*11:01/HLA-A*24:02. To dissect universal CD8(+) T-cell responses, we analysed the magnitude, function and T-cell receptor (TCR) clonality of HLA-A*02:01-M158(+)CD8(+) T cells. We found comparable IFN-?, TNF and CD107a and TCR?? characteristics in Indigenous and non-Indigenous Australians, suggesting that the ~15% of Indigenous people that express HLA-A*02:01 have universal influenza-specific CD8(+) T-cell immunity. Furthermore, the frequency of an influenza host risk factor, IFITM3-C/C, was comparable between Indigenous Australians and Europeans, suggesting that expression of this allele does not explain increased disease severity at a population level. Our study indicates a need to identify novel influenza-specific CD8(+) T-cell epitopes restricted by HLA-A and HLA-B alleles prevalent in Indigenous populations for the rational design of universal T-cell vaccines.

SUBMITTER: Clemens EB

PROVIDER: S-EPMC4840236 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians.

Clemens E Bridie EB Grant Emma J EJ Wang Zhongfang Z Gras Stephanie S Tipping Peta P Rossjohn Jamie J Miller Adrian A Tong Steven Y C SY Kedzierska Katherine K

Immunology and cell biology 20151023 4

Indigenous populations, including Indigenous Australians, are highly susceptible to severe influenza disease and the underlying mechanisms are unknown. We studied immune and genetic factors that could predicate severe influenza disease in Indigenous Australians enrolled in the LIFT study: looking into influenza T-cell immunity. To examine CD8(+) T-cell immunity, we characterised human leukocyte antigen (HLA) profiles. HLA typing confirmed previous studies showing predominant usage of HLA-A*02:01 ...[more]

PMID: 26493179

Similar Datasets

Project description:OBJECTIVE:To examine the prevalence of atrial fibrillation (AF) and cardiac structural characteristics in Indigenous and non-Indigenous Australians. DESIGN:Retrospective cross-sectional study linking clinical, echocardiography and administrative databases over a 10-year period. SETTING:A tertiary, university teaching hospital in Adelaide, Australia. PARTICIPANTS:Indigenous and non-Indigenous Australians. MAIN OUTCOME MEASURES:AF prevalence and echocardiographic characteristics. RESULTS:Indigenous Australians with AF were significantly younger compared to non-Indigenous Australians (55±13 vs 75±13 years, p<0.001). As a result, racial differences in AF prevalence and left atrial diameter varied according to age. In those under 60 years of age, Indigenous Australians had a significantly greater AF prevalence (2.57 vs1.73%, p<0.001) and left atrial diameters (39±7 vs 37±7 mm, p<0.001) compared to non-Indigenous Australians. In those aged 60 years and above, however, non-Indigenous Australians had significantly greater AF prevalence (9.26 vs 4.61%, p<0.001) and left atrial diameters (39±7 vs 37±7 mm, p<0.001). Left ventricular ejection fractions were less in Indigenous Australians under 60 years of age (49±14 vs 55±11%, p<0.001) and not statistically different in those aged 60 years and above (47±11 vs 52±13, p=0.074) compared to non-Indigenous Australians. Despite their younger age, Indigenous Australians with AF had similar or greater rates of cardiovascular comorbidities than non-Indigenous Australians with AF. CONCLUSIONS:Young Indigenous Australians have a significantly greater prevalence of AF than their non-Indigenous counterparts. In contrast, older non-Indigenous Australians have a greater prevalence of AF compared to their Indigenous counterparts. These observations may be mediated by age-based differences in comorbid cardiovascular conditions, left atrial diameter and left ventricular ejection fraction. Our findings suggest that AF is likely to be contributing to the greater burden of morbidity and mortality experienced by young Indigenous Australians. Further study is required to elucidate whether strategies to prevent and better manage AF in Indigenous Australians may reduce this burden.

Project description:BackgroundCardiovascular diseases contribute substantially to the poor health and reduced life expectancy of Indigenous Australians. Heart failure is a common, disabling, progressive and costly complication of these disorders. The epidemiology of heart failure and the adequacy of relevant health service provision in Indigenous Australians are not well delineated.MethodsA systematic search of the electronic databases PubMed, Embase, Web of Science, Cinahl Plus, Informit and Google Scholar was undertaken in April 2012 for peer-reviewed journal articles relevant to the topic of heart failure in Indigenous Australians. Additionally, a website search was done to identify other pertinent publications, particularly government reports.ResultsThere was a paucity of relevant peer-reviewed research, and government reports dominated the results. Ten journal articles, 1 published conference abstract and 10 reports were eligible for inclusion. Indigenous Australians reportedly have higher morbidity and mortality from heart failure than their non-Indigenous counterparts (age-standardised prevalence ratio 1.7; age-standardised hospital separation ratio ?3; crude per capita hospital expenditure ratio 1.58; age-adjusted mortality ratio >2). Despite the evident disproportionate burden of heart failure in Indigenous Australians, the accuracy of estimation from administrative data is limited by poor indigenous identification, inadequate case ascertainment and exclusion of younger subjects from mortality statistics. A recent journal article specifically documented a high prevalence of heart failure in Central Australian Aboriginal adults (5.3%), noting frequent undiagnosed disease. One study examined barriers to health service provision for Indigenous Australians in the context of heart failure.ConclusionsDespite the shortcomings of available published data, it is clear that Indigenous Australians have an excess burden of heart failure. Emerging data suggest that undiagnosed cases may be common in this population. In order to optimise management and to inform policy, high quality research on heart failure in Indigenous Australians is required to delineate accurate epidemiological indicators and to appraise health service provision.

Dataset Information

Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians.

Publications

Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure