Strong antibody responses to Mycobacterium tuberculosis PE-PGRS62 protein are associated with latent and active tuberculosis

Abstract

Mycobacterium tuberculosis has a unique family of PE-PGRS proteins with conserved N-terminal domains (PE) containing site-specific proline-glutamine residues and polymorphic GC-rich repetitive sequences (PGRS). Tuberculosis (TB) patients produce antibodies against some such proteins, but it is not clear whether these responses correlate with disease. Clinical groups with different mycobacterium exposure were studied for their seroreactivity to PE-PGRS17 and PE-PGRS62 proteins and their respective PE domains. There were minimal antibody responses against both PE domains and full-length PE-PGRS17, even in patients with active TB. However, patients with active and latent TB showed significantly higher PE-PGRS62-specific immunoglobulin G antibody responses than treated TB patients and mycobacterium-reactive TB contacts without latent infection. Latently infected persons had high anti-PE-PGRS62 responses but low responses to the 38-kDa antigen commonly used for TB serology, while treated TB cases showed the opposite response. Thus, patterns of seroreactivity to PE-PGRS62 correlate with clinical status and are associated with latent TB infection.

FIG. 1.

(A) The N-terminal domains (amino acids 1 to 94) of both PE-PGRS17 and PE-PGRS62 proteins have significant homology with the PE domain consensus sequence found in products of other members of the PE multigene family. (B) Western blot analysis of the recombinant proteins using mouse anti-His monoclonal antibodies. Lanes: 1, PE-PGRS17; 2, PE-PGRS62; 3, PE-PGRS17^PE; 4, PE-PGRS62^PE.

FIG. 2.

Serum IgG responses to (A) PE-PGRS17 and (B) PE-PGRS17^PE proteins. Group medians are shown as horizontal bars. By the Kruskal-Wallis test there was no significant difference overall between groups.

FIG. 3.

Serum IgG responses to (A) PE-PGRS62 and (B) PE-PGRS62^PE proteins. Group medians are shown as horizontal bars. By the Kruskal-Wallis test, there was an overall significant difference between groups. Medians were compared pairwise using the Mann-Whitney U test with the Bonferroni correction. **, P < 0.005; ***, P < 0.0005.

FIG. 4.

Serum IgG responses to the M. tuberculosis 38-kDa protein. By the Kruskal-Wallis test, there was an overall significant difference between groups. Medians were compared pairwise using the Mann-Whitney U test with the Bonferroni correction. **, P < 0.005.

FIG. 5.

Correlations between responses to PE-PGRS62 and PE-PGRS62^PE proteins. Regression lines and correlation coefficients are shown; statistics are based on the Spearman rank correlation.