Long Term Kinetics Of Cd19+cd24highcd38high Breg Cells In Lung Transplant Recipients

A functional B cell subset, CD19+CD24highCD38high, has been shown to contribute to the maintenance of the fine equilibrium required for tolerance, reducing the inflammatory responses during autoimmune diseases or unresolved infections. Pivotal to B-reg function is IL-10, which inhibits proinflammatory cytokines, supports T-reg cell differentiation and inhibits of Th17 and Th1 cell. The role of Breg cells in human lung transplantation is not yet elucidated, thus we aimed to analyze long-term kinetics of this subset in a cohort of lung recipients and test its association to several clinical and pharmacological variables (IS, azithromycin, extracorporeal photo-apheresis, infections, CLAD etc). From Jan 2009 to dec 2014, 117 lung transplant recipients were submitted to an immunological follow up (I-FU) (median:70 months):complete peripheral immuno-phenotype, inclusive of CD19+CD24highCD38high Breg cells (1102 determinations were analyzed).Linear OR regression models for repeated measures were used to test the association between B-reg and relevant variables, adjusting for time from Tx. Variables resulted significantly associated toperipheral B-reg cell counts in univariate analysis were: use of mycophenolate mofetil: neg association 0.001; while a pos association was present with Bacterial (0.022)and Fungal (0.042) infections.No association between B-reg cell counts and CLAD occurrence, the use of m-Tor inhibitors, azithromycin or other treatments such as ECP was detected. We suggest that regulatory B cells play a limited role in long-term lung transplant acceptance, being marginally influenced only by mycophenolate-mofetil and by respiratory and extrarespiratory infections.