Short-Time Effect of Alemtuzumab Induction Therapy on B- and T-cell Subsets After Lung Transplantation.

Alemtuzumab is a monoclonal antibody targeting CD52, one of the most predominant antigens on the surface of lymphocytes. It induces cell lysis and leads to a profound immune cell depletion. However, little is known how T- and B-cell repopulate and if there is predominance towards certain subtypes. B- and T cell subsets were analyzed from whole blood samples of 25 patients, prospectively collected at time of listing (=baseline) and 6 months post-transplant. Cell subsets were measured by FACS. Patients received alemtuzumab induction followed by low-dose tacrolimus and steroids. Median age of the cohort was 59 years (51-64) and 36% of patients were female. Underlying diagnoses were COPD (36%), fibrosis (20%), CF (12%), PPH (4%), EAA (12%) and others (16%). B- and T cell counts significantly decreased compared to baseline (p=0.009, p<0.001). Within B cell population, relative frequency of IgM+CD27−CD38high, IgM+CD27+CD38high and regulatory B cells increased 6 months after Tx (p=0.017, p=0.016, p=0.028, respectively). Within T cell population, CD4+ T cells decreased 6 months after Tx (p<0.001), while relative frequency of CD8+ T cells was significantly higher (p<0.001). A detailed analysis revealed a shift towards CD4+CD57+(p=0,002), PD1+CD4+(p<0.001), CD45RA+CD197-CD4+ (p=0.0013), CD45RA−CD197−CD4+ (p<0.001), CD27−CD28+ (p<0.001), CD27+CD28+ (p<0.001), PD1+CD8+ (p<0.001), CD45RA+CD197−CD8+ (p=0.039) and regulatory FoxP3+-T cells (p=0.005) at 6 months after Tx. After alemtuzumab induction therapy, the composition of B and T cell subsets is altered compared to baseline. Expansion of subsets such as PD1 T cells and regulatory B- and T cells suggests an immunomodulatory effect of alemtuzumab on cell repopulation. [ABSTRACT FROM AUTHOR]