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Polina Shindiapina
Ohio State University, USA
ScientificTracks Abstracts: J Immune Disord Ther
Statement of the Problem: HIV-positive (HIV(+)) individuals demonstrate chronic changes in cellular immunity, including depletion of CD4+ T cells, elevation in CD8+ T cells, increased markers of senescence and activation. We hypothesized that HIV profoundly impacts immune reconstitution after treatment of hematologic malignancies. We performed a detailed assessment of immune reconstitution in HIV(+) recipients of autologous (auto-SCT) and allogeneic (allo-SCT) hematopoietic stem cell transplant on the BMT CTN 0803/AMC 071 (n=38) and BMT CTN 0903/AMC (n=17) prospective clinical trials. These were compared to HIV(-) auto-SCT recipients (n=30) and healthy controls (n=71). Methodology & Theoretical Orientation: 5-color flow cytometry of whole blood was performed at days 56, 180 and 365 post-transplant (transplant-recipient cohorts) or at a single time point (healthy controls). Results were analyzed by principal component analysis (PCA), Wilcoxon rank-sum test and feature importance score analysis (FIS). Findings: PCA showed that HIV(+) auto-SCT and allo-SCT recipient immune profiles segregated together and away from HIV(-) auto-SCT recipients and healthy controls. HIV(+) auto-SCT and allo-SCT recipients showed significant differences in 38 and 60 immune cell populations compared to healthy controls on day 56, and 39 and 55 immune cell populations at day 365 post-transplant, respectively (p<0.031). In contrast, 7 immune cell populations were identified as significantly different between HIV(+) auto- and allo-SCT recipients on day 56, and none at 1 year post-transplant (p<0.031). FIS identified activated T cells, cytotoxic T cells (total, naïve, memory, effector higher in HIV(+) cohorts), and naïve, central and effector memory T helper subsets (lower in HIV(+) cohorts) as significantly impacting the difference between HIV(+) cohorts and healthy controls. Conclusion & Significance: HIV(+) auto-SCT and allo-SCT recipients demonstrate features of immune activation and converging immune reconstitution trajectories during the post-transplant year, distinct from HIV(-) auto-SCT recipients and healthy controls, suggesting that controlled HIV status significantly impacts post-SCT immune reconstitution. Clinical significance of these findings requires further study.
Shindiapina is an Assistant Professor at the Division of Hematology, Department of Internal Medicine at the Ohio State University, OH, USA. Dr. Shindiapina is a member of the translational lymphoma research group, together with Dr. Robert Baiocchi. Dr. Shindiapina’s laboratory focuses on immune reconstitution studies in immunocompromised patients with hematologic malignancies and virus-driven lymphomas. Dr. Shindiapina and Dr. Baiocchi are members of the AIDS Malignancy Consortium.
