Abstract
Serology-based tests for tuberculosis (TB) diagnosis, though rapid, efficient and easily implemented, have so far shown unsatisfactory levels of sensitivity and specificity, probably due to variations of the antibody response in TB patients. The number and types of seropositive antigens vary from individual to individual. The person-to-person variations of antigen recognition may be linked to genetic polymorphisms of the human leukocyte antigen (HLA) class II alleles. In the present study, we find that there is a significant increase in the frequency of HLA-DRB1*14 (P = 2.5×10−4) among subjects with high antibody response levels compared to those with low antibody levels. HLA-DRB1*15, the most frequent allelic group in the studied active TB population, positively correlates with subjects with low antibody response levels rather than subjects with high antibody response levels (P = 0.005), which indicates the loss of relevant antigens for screening of patients with this allelic group. The potential association between HLA-DRB1 allelic group and individual antigens implies that TB diagnostic yield could be improved by the addition of antigens screened at the proteome scale in infected subjects from the HLA-DRB1*15 allelic group.
Highlights
Despite substantial progress toward the goal of tuberculosis (TB) elimination, it continues to be one of the most prevalent infectious diseases worldwide, especially in developing countries
The active TB case was defined as a patient with a positive sputum culture for the M. tuberculosis complex or a patient who has been diagnosed with active TB by a clinician and has been decided to have TB treatment according to clinical diagnostic criteria
Since we found that human leukocyte antigen (HLA)-DRB1Ã15, the highest frequency allele (18.32%) in whole studied active TB population, positively correlated with subjects with low antibody response levels rather than subjects with high antibody response levels (P = 0.005), which implies the loss of relevant antigens for screening of patients with this allelic group, it was necessary to investigate the potential association between the HLA-DRB1 alleles and antibody response to individual antigens
Summary
Despite substantial progress toward the goal of tuberculosis (TB) elimination, it continues to be one of the most prevalent infectious diseases worldwide, especially in developing countries. There is some evidence that the HLA alleles play a crucial role in the modulation of the immune response and can influence the outcome of TB infection [29, 30]. Other infectious diseases, such as hepatitis B and malaria, are found to show association between HLA class II genes and antibody response to relevant antigens [31,32,33]. We evaluate the potential influence of HLA-DRB1 alleles on the variations of antibody response to TB serodiagnostic antigens in active TB patients
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