Immune Profile Of Sickle Cell Anemia Patients Treated With Allogeneic Stem Cell Transplantation

BLOOD(2017)

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摘要
Sickle cell disease (SCD) is one the most common recessive monogenic disease in the world. In the last years, SCD patients have been successfully treated with allogeneic hematopoietic stem cell transplantation (HSCT), the only curative option to date. However, the immune reconstitution mechanisms involved in therapeutic response of HSCT in SCA patients are not elucidated yet. For that, blood samples from SCD patients (N=24) were collected before (pre-tx) and until 1 year after transplantation (1 month, 3, 6 and 12 months) and immune cell subpopulations were analyzed by flow cytometry. In addition, peripheral blood mononuclear cells from 4 SCD patients and 4 healthy individuals were isolated, RNA was isolated and cDNA synthetized, and expression of genes associated with inflammatory response was evaluated by PCR array. Serum cytokines/chemokine levels were also measured in SCD patients by luminex assays. We observed decreased number of total lymphocytes until 3 months after HSCT (mean±SD: 1496±1012 cells/uL) compared to pre-tx (2671±924.8; p + T cell number decreased until 6 months after transplantation (pre-tx: 182.6±146.9; 6 months: 91.33±90,42; p + T cell until 3 months (pre-tx: 224.7±160; 3 months: 77.42±75.74; p + T cell increased 6 months after HSCT (pre-tx: 20.03±18.67; 6 months: 39.89±31.24; p + T cell 12 months (pre-tx: 64.83±64.97; 12 months: 174.7±193.2; p + CD25 + CTLA-4 + T cell (pre-tx: 118.5±95.16; 6 months: 54.37±42.25) and CD4 + CD25 + Foxp3 + T cell (pre-tx: 112.4±78.96; 6 months: 56.55±46.84) decreased until 6 months after transplantation compared to pre-tx (p + CD25 + GITR + T cell and CD8 + CD28 - Foxp3 + T cell did not change after transplant. However, increased number of CD8 + CD28 - T cells was observed 6 (307.6±382.6) and 12 months (373.3±357.5) after transplantation compared to pre-tx (120.8±133.8) and CD8 + CD28 - CD57 + T cells raised 12 months (pre-tx: 52.69±92.86; 12 months: 160.5±175.9; p Disclosures Hermine: AB Science: Equity Ownership, Honoraria, Patents u0026 Royalties, Research Funding; Hybrigenics: Research Funding; Novartis: Research Funding; INatherys: Equity Ownership, Research Funding; Celgene: Research Funding.
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