The Antibody Response to Primary Tuberculous Infection in Man

Abstract

The unitary concept of tuberculosis in man contends that the primary infection is associated with hematogenous dissemination of bacilli. To test whether dissemination might elicit an antibody response and whether serologic study might identify primary tuberculous infection, the pattern of antibody response was obtained in 141 persons: 28 patients with smear-positive, culture-positive (S + C +) pulmonary tuberculosis (PTB), 3 patients with smear-negative, culture-positive (S – C +) disseminated tuberculosis, 5 patients with S – C + PTB, 9 contacts with tuberculin conversion within 1 year, 79 tuberculin reactor contacts with unknown previous tuberculin status who were exposed (possible converters), and 17 healthy control subjects (13 tuberculin reactors with unknown previous tuberculin status who were not exposed, 2 tuberculin reactors who were known reactors for longer than 2 years, and 2 tuberculin nonreactors). Serum antibodies competed with 6 radiolabeled monoclonal antibodies (Mab) for binding to a solid phase coated soluble extract of Mycobacterium tuberculosis. ’Sera were considered positive when the 50% inhibiting antibody titers of one or more Mab exceeded the established cutoff point. This gave a positive result in 27 (96%) patients with S + C + PTB, 3 (100%) S – C + patients with disseminated tuberculosis, and 3 (60%) patients with S – C+ PTB using a 4-probe combination of TB 68, TB 71, TB 72, and TB 78. This same combination gave a positive result in 9 (100%) patients with primary tuberculous infection and in 16 (84%) young (≤17 years) tuberculin reactor contacts with unknown previous tuberculin status who were exposed (probable primary infection) but not in 2 similar contacts who were known tuberculin reactors for longer than 2 years. The serologic results support the hypothesis that the primary tuberculous infection is disseminated. Serologic examination may be a useful method of identifying patients with primary infection.