Pathophysiology of antigen 85 in patients with active tuberculosis: Antigen 85 circulates as complexes with fibronectin and immunoglobulin G

Antigen 85 (Ag85) complex proteins are major secretory products of Mycobact erium tuberculosis and induce strong cellular and humoral immune responses in infected experimental animals and human beings. We have previously shown that nanogram doses of these 30- to 32-kDa fibronectin-binding proteins in hibit local expression of delayed hypersensitivity by a T-cell fibronectin- dependent mechanism. Circulating levels of Ag85 might be expected to be ele vated in patients with active tuberculosis and possibly to play a role in s ystemic anergy in these patients. To test this hypothesis, Ag85 was measure d in serum and urine by a monoclonal antibody-based dot immunobinding assay in 56 patients and controls with known skin test reactivity. Median serum Ag85 levels were 50- to 150-fold higher in patients with active tuberculosi s than in patients with active M. avium-intracellulare disease or other non tuberculous pulmonary disease or in healthy controls (P < 0.001). The media n and range of serum Ag85 in patients with active tuberculosis was not sign ificantly different between skin test-positive and -negative subjects. Pati ents with active M. avium disease could be distinguished from those with di sease due to M. tuberculosis by monoclonal anti-Ag85 antibodies of appropri ate specificities. No increases in urinary Ag85 were detected in any patien t, regardless of the Ag85 level in serum. Chromatographic analysis and immu noprecipitation studies of serum revealed that Ag85 existed in the serum of these patients complexed to either fibronectin or immunoglobulin G (Igc). Uncomplexed circulating Ag85 was demonstrable in serum from fewer than 20% of patients with active tuberculosis. In patients with active tuberculosis, Ag85 is therefore likely to circulate primarily as complexes with plasma f ibronectin and IgG rather than in unbound form. The existence of Ag85 compl exes with plasma proteins would account for its lack of urinary clearance.