Use of antibodies in lymphocyte secretions for detection of subclinical tuberculosis infection in asymptomatic contacts

Abstract

We have previously demonstrated that Mycobacterium bovis BCG-specific immunoglobulin G antibodies in lymphocyte secretions (ALS) can be employed as a marker for active tuberculosis (TB). We aimed to determine whether the ALS method allows detection of subclinical TB infection in asymptomatic individuals. A prospective study of family contacts (FCs) of patients with active TB and healthy controls was performed. Thirteen of 42 FCs had high ALS responses, including 6 FCs who subsequently developed active TB. No correlation was observed between the tuberculin skin test and the ALS responses in the FCs (r = 0.1, P = 0.23). Among patients with active TB, BCG-specific ALS responses steadily declined from the time of diagnosis through 6 months following antimycobacterial chemotherapy (P = 0.001). The ALS assay enabled detection of infection in exposed symptom-free contacts, who are at greater risk for developing active TB. The method may also allow discrimination between effective treatment of active infection and suboptimal response to therapy.

FIG. 1.

BCG-specific IgG ALS responses (relative titers) in lymphocyte secretions in FCs of patients with active TB (index cases) on day 1 and at 2 and 6 months after enrollment. Nine FCs (arrows labeled 1 to 9) who had specific IgG ALS responses above the cutoff level at the different time intervals are identified. FCs 1 to 6 later developed clinical symptoms and were given antimycobacterial treatment. FCs 7 to 9 were sputum culture negative and did not develop TB; their ALS responses were below the cutoff at 6 months. Three additional contacts had high ALS responses at day 180 and were not monitored thereafter.

FIG. 2.

Comparison of BCG-specific IgG ALS responses (relative titers) in lymphocyte secretions from index cases at different time points during the course of the disease. Short bars represent GM titers of specific IgG for the groups. Specific IgG ALS responses at 2 and 6 months were significantly lower than those on day 1 (marked by asterisks). Patients had significantly higher ALS responses at all time points than BHC (P = 0.001) and SHC (P = 0.009). Statistical comparison between groups was performed using the one-way ANOVA or ANOVA on ranks.