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

Abstract

<h3>Purpose</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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⁻CD38^high, IgM⁺CD27⁺CD38^high 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. <h3>Conclusion</h3> 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.