Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May:67:103346.
doi: 10.1016/j.ebiom.2021.103346. Epub 2021 Apr 25.

HLA class I and II associations with common enteric pathogens in the first year of life

Sayo E McCowin  1 , G Brett Moreau  2 , Rashidul Haque  2 , Janelle A Noble  3 , Shana L McDevitt  4 , Jeffrey R Donowitz  5 , Md Masud Alam  1 , Beth D Kirkpatrick  6 , William A Petri  7 , Chelsea Marie  8
Affiliations

HLA class I and II associations with common enteric pathogens in the first year of life

Sayo E McCowin et al. EBioMedicine. 2021 May.

Abstract

Background: genetic susceptibility to infection is mediated by numerous host factors, including the highly diverse, classical human leukocyte antigen (HLA) genes, which are critical genetic determinants of immunity. We systematically evaluated the effect of HLA alleles and haplotypes on susceptibility to 12 common enteric infections in children during the first year of life in an urban slum of Dhaka, Bangladesh.

Methods: a birth cohort of 601 Bangladeshi infants was prospectively monitored for diarrhoeal disease. Each diarrhoeal stool sample was analyzed for enteric pathogens by multiplex TaqMan Array Card (TAC). High resolution genotyping of HLA class I (A and B) and II (DRB1, DQA1, and DQB1) genes was performed by next-generation sequencing. We compared the frequency of HLA alleles and haplotypes between infected and uninfected children.

Findings: we identified six individual allele associations and one five-locus haplotype association. One allele was associated with protection: A*24:02 - EAEC. Five alleles were associated with increased risk: A*24:17 - typical EPEC, B*15:01 - astrovirus, B*38:02 - astrovirus, B*38:02 - Cryptosporidium and DQA1*01:01 - Cryptosporidium. A single five-locus haplotype was associated with protection: A*11:01~B*15:02~DRB1*12:02~DQA1*06:01~DQB1*03:01- adenovirus 40/41.

Interpretation: our findings suggest a role for HLA in susceptibility to early enteric infection for five pathogens. Understanding the genetic contribution of HLA in susceptibility has important implications in vaccine design and understanding regional differences in incidence of enteric infection.

Funding: this research was supported by the National Institute of Health (NIH) and the Bill and Melinda Gates Foundation.

Keywords: Bangladesh; Children; Diarrhoea; HLA; Infection; Susceptibility.

PubMed Disclaimer

Conflict of interest statement

Declaration of Competing Interest JD reports grants from National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development, grants from the Bill and Melinda Gates Foundation, grants from Pantheryx, Inc, outside the submitted work. WAP reports grants from NIH and grants from Gates Foundation, during the conduct of the study; other grants from TechLab outside the submitted work. CM reports grants from the NIH and funding from Bill and Melinda Gates Foundation, during the conduct of the study. All other authors have nothing to disclose.

Figures

Fig 1
Fig. 1
HLA class I and II allele enteric pathogen associations: Associations between five HLA loci (A~B~DRB1~DQA1~DQB1) analyzed and the 12 most common enteric infections in a cohort of 601 infants during the first year of life. Pathogens are arranged by class (bacteria, virus, protozoa). Odds-ratios (OR) for HLA-pathogen associations with P-value <0•05 are shown. Red = increased susceptibility to infection, blue = decreased susceptibility to infection. Bolded boxes indicate significant HLA-pathogen associations after correction for multiple comparisons (FDR<0•15). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
See this image and copyright information in PMC

References

    1. Petri W.A., Miller M., Binder H.J., Levine M.M., Dillingham R., Guerrant RL. Enteric infections, diarrhea, and their impact on function and development. J Clin Invest. 2008;118(4):1277–1290. [Internet]1172Available from: 10. - PMC - PubMed
    1. Troeger C., Colombara D.V., Rao P.C., Khalil I.A., Brown A., Brewer T.G. Global disability-adjusted life-year estimates of long-term health burden and undernutrition attributable to diarrheal diseases in children younger than 5 years. Lancet Glob Health. 2018;6(3):e255–e269. - PMC - PubMed
    1. Checkley W., Buckley G., Gilman R.H., Assis A.M., Guerrant R.L., Morris S.S. Multi-country analysis of the effects of diarrhea on childhood stunting. Int J Epidemiol. 2008;37(4):816–830. - PMC - PubMed
    1. Nataro J.P., Guerrant RL. Chronic consequences on human health induced by microbial pathogens: growth faltering among children in developing countries. Vaccine. 2017;35(49):6807–6812. - PubMed
    1. Kotloff K.L., Nataro J.P., Blackwelder W.C., Nasrin D., Farag T.H., Panchalingam S. Burden and aetiology of diarrheal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet. 2013;382(9888):209–222. - PubMed

Substances