Antigens of Mycobacterium tuberculosis recognized by antibodies during incipient, subclinical tuberculosis

Abstract

Serum samples obtained from human immunodeficiency virus (HIV)-infected tuberculosis (TB) patients months prior to clinical TB were used to delineate the profile of Mycobacterium tuberculosis culture filtrate proteins recognized during subclinical TB. A subset of approximately 12 antigens was recognized by antibodies in these serum samples. Antibodies to two of these antigens (81 [88]-kDa malate synthase [GlcB] and MPT51) were present in serum samples obtained during incipient subclinical TB in 19 (approximately 90%) of the 21 HIV-infected TB patients tested. These antigens will be useful for devising diagnostic tests that can identify HIV-positive individuals who are at a high risk for developing clinical TB.

FIG. 1.

Reactivity of fractionated CFPs with pooled serum samples from healthy, PPD skin test-positive individuals (A) and subclinical TB serum samples from HIV⁺ TB⁺ individuals (B). Antigens recognized by both serum pools are circled in blue; antigens recognized only during subclinical TB are circled in green. The antigen circled in red is a 38-kDa protein previously shown to be recognized primarily by cavitary TB patients (15). Molecular masses (kilodaltons) are indicated at the left of each panel. Panel C shows the reactivity of serum samples with the purified 81 (88)-kDa (striped bars) and MPT51 (hatched bars) proteins. The solid bars show additive reactivity with both antigens. Panel D shows the reactivity of paired serum specimens obtained from each individual during subclinical TB and at the time of diagnosis of clinical TB. The ΔOD (OD obtained with any serum specimen minus the cutoff, which was calculated as the mean OD of the control group plus 3 standard deviations) for each specimen is plotted.