Introduction: Immunodeficiency associated with thymoma, known as Good's syndrome (GS), is characterized by recurrent severe infections and hypogammaglobulinemia/ B lymphopenia. Involvement of both B cell and T cell dysfunction has been reported but the molecular mechanism of impaired response to infection remains unclear.
Purpose: To elucidate the role of immune checkpoint molecules in the pathogenesis of immunodeficiency in GS.
Method: Peripheral blood mononuclear cells from thymoma-associated myasthenia gravis (TAMG) patients (n=18) were evaluated. TAMG patients with at least two previous episodes of infections requiring hospitalization (GS) and those without (non-GS) were compared to age-matched disease-free controls.
Results: PD-1 expression on CD4+Foxp3+ cells (Tregs) was increased in GS patients (n=8) compared to controls (n=10) but not in non-GS patients (n=10) (p < 0.05, Mann-Whitney U test). PD-1+Tim-3+ Tregs were also increased in GS. The mean fluorescence intensity of PD-1 on Tregs was significantly higher in GS than in controls and was negatively correlated with B cell frequency (Rs=-0.81, p=0.01, Spearman's correlation coefficient). Cell viability assay on B cells by anti-CD40 antibody stimulation revealed that co-culture with autologous Tregs increased Annexin-V negative necrotic cell number (p < 0.01, Wilcoxon signed-rank test). A partial reversal of the effect was observed by anti-PD-L1 antibody, however, it was not statistically significant. Discussion/
Conclusion: The role of check point molecules on Tregs is still under debate. We propose that the upregulation of PD-1+ on Tregs is involved in dampening immune response in TAMG. Suppression of B cell survival by Tregs may be a factor contributing to B cell dysfunction in GS.
