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

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

1. Muneeb Salie1, 
2. Lize van der Merwe1,2,3, 
3. Marlo Möller1, 
4. Michelle Daya1,
5. Gian D. van der Spuy1, 
6. Paul D. van Helden1, 
7. Maureen P. Martin4,5,
8. Xiao-jiang Gao4,5, 
9. Robin M. Warren1, 
10. Mary Carrington4,5 and 
11. Eileen G. Hoal1

1. ¹MRC Centre for Molecular and Cellular Biology and the DST/NRF Centre of Excellence for Biomedical TB Research, Division of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg
2. ²MRC Biostatistics Unit, Medical Research Council, Tygerberg
3. ³Department of Statistics, University of Western Cape, Bellville, South Africa
4. ⁴Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick, Inc, Frederick National Laboratory for Cancer Research, Frederick, Maryland
5. ⁵Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge

1. Correspondence: Eileen G. Hoal, PhD, Francie van Zijl Drive, Fisan Building, 4th Floor, Room F417, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa (egvh{at}sun.ac.za).

Abstract

Background. The development of active tuberculosis disease has been shown to be multifactorial. Interactions between host and bacterial genotype may influence disease outcome, with some studies indicating the adaptation of M. tuberculosis strains to specific human populations. Here we investigate the role of the human leukocyte antigen (HLA) class I genes in this biological process.

Methods. Three hundred patients with tuberculosis from South Africa were typed for their HLA class I alleles by direct sequencing.Mycobacterium tuberculosis genotype classification was done by IS6110restriction fragment length polymorphism genotyping and spoligotyping.

Results. We showed that Beijing strain occurred more frequently in individuals with multiple disease episodes (P < .001) with the HLA-B27allele lowering the odds of having an additional episode (odds ratio, 0.21;P = .006). Associations were also identified for specific HLA types and disease caused by the Beijing, LAM, LCC, and Quebec strains. HLA types were also associated with disease caused by strains from the Euro-American or East Asian lineages, and the frequencies of these alleles in their sympatric human populations identified potential coevolutionary events between host and pathogen.

Conclusions. 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.

Key words

• Mycobacterium tuberculosis
 
• tuberculosis
 
• human leukocyte antigens
• host–pathogen
 
• coadaptation
 
• susceptibility