Elevated serum antibody responses to synthetic mycobacterial lipid antigens among UK farmers: an indication of exposure to environmental mycobacteria?

Abstract

Background: mycobacterial cells contain complex mixtures of mycolic acid esters. These can be used as antigens recognised by antibodies in the serum of individuals with active tuberculosis, caused by Mycobacterium tuberculosis. In high burden populations, a significant number of false positives are observed; possibly these antigens are also recognised by antibodies generated by other mycobacterial infections, particularly ubiquitous 'environmental mycobacteria'. This suggests similar responses may be observed in a low burden TB population, particularly in groups regularly exposed to mycobacteria. Methods: ELISA using single synthetic trehalose mycolates corresponding to major classes in many mycobacteria was used to detect antibodies in serum of individuals with no known mycobacterial infection, comprising farmers, abattoir workers, and rural and urban populations. Results: serum from four Welsh or Scottish cohorts showed lower (with some antigens significantly lower) median responses than those reported for TB negatives from high-burden TB populations, and significantly lower responses than those with active TB. A small fraction, particularly older farmers, showed strong responses. A second study examined BCG vaccinated and non-vaccinated farmers and non-farmers. Farmers gave significantly higher median responses than non-farmers with three of five antigens, while there was no significant difference between vaccinated or non-vaccinated for either farmer or non-farmer groups. Conclusions: this initial study shows that serodiagnosis with mycobacterial lipid antigens can detect antibodies in a population sub-group that is significantly exposed to mycobacteria, in an assay that is not interfered with by vaccination. Given the links between mycobacterial exposure and a range of immune system diseases, further understanding such responses may provide a new opportunity for monitoring public health and directing treatment.

Fig. 1. Typical mycolic acid structure.

Fig. 2. Antigens known to distinguish active TB from not active TB in high burden populations, and used in this study.

Scheme 1. Study plan: initial study.

Scheme 2. Second study: Welsh farmers and non-farmers with vaccination status.

Fig. 3. Dot plots of responses for each set of serum samples with six antigens and the total response.

Fig. 4. Distribution of ELISA responses for each set of Welsh samples by age in years for each single antigen and the total response, with trend lines.