Osteopontin expression correlates with clinical outcome in patients with mycobacterial infection

Osteopontin (OPN) is a protein flat Is expressed in chronic Inflammatory di seases including tuberculosis, and its deficiency predisposes to more sever e mycobacterial Infections in mice. However, no reports have identified alt ered OPN expression in, or correlated these alterations to, infections in h umans. The data presented herein identify alterations in the tissue express ion of OPN protein and describe an inverse correlation between these levels and disease progression after inoculation of Mycobacterium bovis bacillus Calmette-Guerin vaccine in humans. Patients with regional adenitis and good clinical outcomes had abundant OPN in infected lymph nodes. This pattern o f OPN accumulation was also observed in patients infected by M. avium-intra cellulare. In contrast, patients with disseminated infection and histologic ally ill-defined granulomas had no significant osteopontin accumulation in infected lymph nodes; these patients had either deficiencies in the interfe ron-gamma receptor 1 or idiopathic Immune defects, The level of OPN protein expression was inversely correlated with disseminated infection and, of pa rticular interest, with death of the patient. We conclude that osteopontin expression correlates with an effective immune and inflammatory response wh en humans are challenged by a mycobacterial infection and that osteopontin contributes to human resistance against mycobacteria.