Altered expression of TAP-1 and major histocompatibility complex class I in laryngeal papillomatosis: Correlation of TAP-1 with disease

Recurrent respiratory papillomatosis (RRP) is an insidious disease caused b y human papillomavirus (HPV) infection. It is characterized by a variable c linical course that can include frequent disease recurrence, significant mo rbidity, and occasional mortality, The mechanisms responsible for the varia bility in the clinical course and the persistence of latent HPV infection r emain unknown. Effective T-cell-mediated clearance of HPV-infected cells ma y be defective in patients with RRP, leading to recurrent disease and failu re to suppress Latent HPV reactivation. This study describes the down-regul ation of the transporter associated with antigen presentation (TAP-1) and t he major histocompatibility complex (MHC) class I protein expression in lar yngeal papilloma tissue biopsies and cell culture of primary explants. Ther e was a statistically significant correlation between reduction of TAP-1 ex pression in biopsy tissues and rapid recurrence of disease. Patients with R RP had less frequent recurrence if their papillomas expressed TAP-1 at leve ls close to that of normal tissue, compared with those with very low expres sion of TAP-1, who had frequent recurrence (32 versus 5 weeks to the next s urgical intervention). These findings suggest that HPV may evade immune rec ognition by down-regulating class I MHC cell surface expression via decreas ed TAP-1 levels. Expression of TAP-1 could be used for prognostic evaluatio n of disease severity. Gamma interferon was able to restore class I MHC exp ression at the surfaces of laryngeal papilloma cells in culture. This up-re gulation of class I MHC antigen at the cell surface potentially allows the infected cell to become a target for the immune system again. This finding provides some promise for nonsurgical treatment of laryngeal papillomas.