Peribronchial tertiary lymphoid structures persist after rituximab therapy in patients with cystic fibrosis

Tertiary lymphoid structures (TLS) are usually absent in normal lungs, but peribronchial TLS are found in the lungs of patients with bronchiectasis or cystic fibrosis (CF).1 Recently, our group reported studies in mice showing that persistent bacterial infection induced peribronchial TLS, suggesting that chronic infection is a major trigger of lymphoid neogenesis in CF airways.1 However, roles of TLS in the pathogenesis of CF lung disease remain unknown and could include beneficial antimicrobial effects and/or autoimmune responses leading to tissue damage and disease worsening.2 Like secondary lymphoid organs, TLS exhibit B cell area containing follicular dendritic cells (FDC) and germinal centres, surrounded by T cells and high endothelial venules (HEV).2 Rituximab, a chimeric monoclonal antibody targeting CD20+ B cells, is used as treatment for malignant lymphoproliferative disorders and for autoimmune diseases3 and has also been used in highly sensitised patients undergoing solid organ transplantation.4 This strategy was once believed to be beneficial for sensitised lung transplant recipients but was abandoned years ago due to results showing that rituximab-based desensitisation protocol did not reduce pretransplant anti-HLA antibodies.5 In the present study, we took advantage of bronchial explants collected in two patients with CF who had received rituximab and human polyclonal intravenous immunoglobulin for high HLA-sensitisation prior to lung transplantation to examine the effects of rituximab on peribronchial TLS. Our hypothesis was that rituximab therapy, which …