The Effect of Single and Combined Activating Killer Immunoglobulin-like Receptor Genotypes on Cytomegalovirus Infection and Immunity after Hematopoietic.

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Presentation transcript:

The Effect of Single and Combined Activating Killer Immunoglobulin-like Receptor Genotypes on Cytomegalovirus Infection and Immunity after Hematopoietic Cell Transplantation John A. Zaia, Joel Y. Sun, Ghislaine M. Gallez-Hawkins, Lia Thao, Arisa Oki, Simon F. Lacey, Andrew Dagis, Joycelynne Palmer, Don J. Diamond, Stephen J. Forman, David Senitzer Biology of Blood and Marrow Transplantation Volume 15, Issue 3, Pages 315-325 (March 2009) DOI: 10.1016/j.bbmt.2008.11.030 Copyright © 2009 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 1 Donor and recipient KIR gene frequency in HCT recipients with and without CMV reactivation. The cohort has been dichotomized according to the recipient's CMV reactivation status (solid columns, n = 152, having at least 1 incident of CMV reactivation; and stripped columns, n = 59, having no CMV reactivation). The KIR gene frequency is separately portrayed for donors (A) and recipients (B). aKIR2DS4d represents the deletion variant of aKIR2DS4. iKIR2DL4, iKIR3DL2, and iKIR3DL3 were detected in all members of this cohort, and thus omitted from this figure. AA indicates individuals homozygous for KIR haplotype A, and BX indicates individuals either heterozygous (BA) or homozygous (BB) for KIR haplotype B. ∗P = .06, ∗∗P ≤ .05 using the chi-square test. Biology of Blood and Marrow Transplantation 2009 15, 315-325DOI: (10.1016/j.bbmt.2008.11.030) Copyright © 2009 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 2 CMV reactivation and aKIR profiles. (A) Percent CMV reactivation versus number of donor aKIR genes: 0 donor aKIR (n = 30), 1-4 donor aKIR (n = 161) and equal to 5 or more aKIR (n = 20). Chi-square t-test is significant for independence, P = .034. (B) Percent CMV reactivation versus type of donor aKIR combinations, including No aKIR2DS2 or aKIR2DS4 (n = 57), either aKIR2DS2 or aKIR2DS4 (n = 118), and both aKIR2DS2 and aKIR2DS4 (n = 36). Chi-square t-test is significant for independence, P = .001. Biology of Blood and Marrow Transplantation 2009 15, 315-325DOI: (10.1016/j.bbmt.2008.11.030) Copyright © 2009 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 3 CMV reactivation profile for each Group I, II, and III. (A) Time to first CMV positivity by Q-PCR is shown for subjects in each group (log-rank test P = .004). (B) Time to peak Q-PCR is shown for subjects in each group (log-rank test P = .015). (C) Amounts of CMV genome copies/mL are shown at time of first detected CMV reactivation (Kruskal-Wallis test, P = .0001). (D) Peak amounts of CMV genome copies/mL are shown (Kruskal-Wallis test, P < .0002). Biology of Blood and Marrow Transplantation 2009 15, 315-325DOI: (10.1016/j.bbmt.2008.11.030) Copyright © 2009 American Society for Blood and Marrow Transplantation Terms and Conditions

Figure 4 Adaptive immune response in Groups I, II, and III. The adaptive immune response was analyzed at days 40, 90, 120, 150, 180, and 360 post-HCT for Groups I, II, and III. (A) Time to first 1 × 106 CD8+/IFN-γ+ cells/L as determined by in vitro assay after stimulation with a CMV-pp65 peptide mixture or 1 to 2 peptides specific for HLA A∗0201 and or B∗07. (B) Time to first 1 × 106 CD8+/IFN-γ+ cells/L as determined in vitro after stimulation with a CMV-IE1 peptide mixture or 3 peptides specific for HLA A∗0201 and or ∗B08. (C) Time to first 1 × 106 CD4+/IFN-γ+ cells/L as determined by in vitro assay after stimulation with a CMV antigen cell lysate. Biology of Blood and Marrow Transplantation 2009 15, 315-325DOI: (10.1016/j.bbmt.2008.11.030) Copyright © 2009 American Society for Blood and Marrow Transplantation Terms and Conditions