Due to the lack of HLA-matched donors, haploidentical related donor transplantation (HSCT) has been increasingly utilized in high-risk hematologic patients. Recent evidences suggest that non-HLA immune-associated genes are also implicated in the clinical outcome after allo-SCT. In our laboratory, we are interested in studying the FcgammaRIII A (CD16), a low affinity receptor for monomeric IgG, preferentially expressed on NK cells, and on subsets of monocytes and T cells. According to the literature, CD16 is mainly composed of 5 polymorphic molecules with a variable binding affinity for the IgG Fc fragment which could lead to a modulation of antibody dependenT cellular cytotoxicity (ADCC). Since there is evidence that CD16A-158V/F and CD16A-48L/H/R polymorphisms could influencethe outcome of homozygous leukemic patients undergoing HLAfully matched unrelated SCT transplantation, we have hypothesizedthat CD16A polymorphisms could also have an impact onnon T cell depleted HSCT outcome. In this preliminary study,we have evaluated the frequency of CD16 polymorphisms in16 unmanipulated donor/recipient pairs. DNA was isolated fromperipheral blood, and CD16A-48 and -158 polymorphisms wereanalyzed utilizing a sequence based typing (SBT) assay. Whenpossible, the indicated CD16 polymorphisms were evaluatedbefore, and 1, 3 and 12 months after transplant. Eight patientsare alive and disease-free with a median follow-up of 12 months,4 died of acute GvHD and 4 died of infections. Seventy fivepercent of recipients (12) and 69% of donors (11) had CD16AA-158V/F respectively, while 25% of recipients (4) and 31% ofdonors (5) had CD16A-158V/V respectively. Interestingly, noneof recipients and donors had CD16A-158F/F. In recipients,CD16A-48 polymorphism included 68% L/L (11), 6% L/H (1),19% L/R (3) and 6% H/R (1) while donors CD16A48 involved75% L/L (12), 6% L/H (1), 12.5% LR (2), and 0%H/R. A clearlinkage between the CD16A-48 and CD16A-158 polymorphismswas observed since 10 of 16 patients with CD16A-158F/V werealso CD16A-48L/L. In addition, since there were only 3 informativedonor/recipient pairs with differences in CD16A polymorphisms,of which only 1 patient survived, it would be criticalto increase case numbers in order to understand the influence of donor mis-matched CD16A genotype on clinical transplantation outcomes.
FREQUENCY OF FCGRIIIA POLYMORPHISMS IN NONT CELL DEPLETED HAPLOIDENTICAL STEM CELL TRANSPLANTATION
Anna Aureli;Angelica Canossi;Tiziana Del Beato;Giuseppe Sconocchia
2012
Abstract
Due to the lack of HLA-matched donors, haploidentical related donor transplantation (HSCT) has been increasingly utilized in high-risk hematologic patients. Recent evidences suggest that non-HLA immune-associated genes are also implicated in the clinical outcome after allo-SCT. In our laboratory, we are interested in studying the FcgammaRIII A (CD16), a low affinity receptor for monomeric IgG, preferentially expressed on NK cells, and on subsets of monocytes and T cells. According to the literature, CD16 is mainly composed of 5 polymorphic molecules with a variable binding affinity for the IgG Fc fragment which could lead to a modulation of antibody dependenT cellular cytotoxicity (ADCC). Since there is evidence that CD16A-158V/F and CD16A-48L/H/R polymorphisms could influencethe outcome of homozygous leukemic patients undergoing HLAfully matched unrelated SCT transplantation, we have hypothesizedthat CD16A polymorphisms could also have an impact onnon T cell depleted HSCT outcome. In this preliminary study,we have evaluated the frequency of CD16 polymorphisms in16 unmanipulated donor/recipient pairs. DNA was isolated fromperipheral blood, and CD16A-48 and -158 polymorphisms wereanalyzed utilizing a sequence based typing (SBT) assay. Whenpossible, the indicated CD16 polymorphisms were evaluatedbefore, and 1, 3 and 12 months after transplant. Eight patientsare alive and disease-free with a median follow-up of 12 months,4 died of acute GvHD and 4 died of infections. Seventy fivepercent of recipients (12) and 69% of donors (11) had CD16AA-158V/F respectively, while 25% of recipients (4) and 31% ofdonors (5) had CD16A-158V/V respectively. Interestingly, noneof recipients and donors had CD16A-158F/F. In recipients,CD16A-48 polymorphism included 68% L/L (11), 6% L/H (1),19% L/R (3) and 6% H/R (1) while donors CD16A48 involved75% L/L (12), 6% L/H (1), 12.5% LR (2), and 0%H/R. A clearlinkage between the CD16A-48 and CD16A-158 polymorphismswas observed since 10 of 16 patients with CD16A-158F/V werealso CD16A-48L/L. In addition, since there were only 3 informativedonor/recipient pairs with differences in CD16A polymorphisms,of which only 1 patient survived, it would be criticalto increase case numbers in order to understand the influence of donor mis-matched CD16A genotype on clinical transplantation outcomes.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
