Expression of IDO1 and PD-L2 in Patients with Benign Lymphadenopathies and Association with Autoimmune Diseases

The expression patterns of IDO1 and PD-L2 have not been thoroughly investigated in benign lymphadenopathies. The aim with this study was to elucidate how IDO1 and PD-L2 are expressed in benign lymphadenopathies in patients with autoimmune diseases (AD) compared to patients without AD. Formalin-fixed paraffin-embedded lymph nodes from 22 patients with AD and 57 patients without AD were immunohistochemically stained to detect IDO1 and PD-L2. The material was previously stained with EBER in situ hybridization to detect cells harboring the Epstein-Barr virus (EBV). IDO1 and PD-L2 were generally expressed by leukocytes to low degrees, while follicular IDO1+ cells were very rare. IDO1+ cells in single germinal centers were detected in five patients, and there was a high co-occurrence of follicular EBV+ cells in these cases (three of five patients). There were also significant correlations between interfollicular EBV+ cells and interfollicular IDO1+ cells (Spearman rho = 0.32, p = 0.004) and follicular IDO1+ cells (Spearman rho = 0.34, p = 0.004). High or low amounts of IDO1+ or PD-L2+ cells were not statistically significantly associated with patients with AD. However, the lymphadenopathy with the highest amount of interfollicular IDO1+ cells, which was also the only lymphadenopathy in which endothelial cells expressed IDO1, was in a patient with sarcoidosis. This study further supports that the EBV induces the expression of IDO1 and our findings should be recognized by future studies on IDO1 and PD-L2 in inflammatory and malignant conditions.