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Characterization of natural killer cells expressing markers associated with maturity and cytotoxicity in children and young adults with sickle cell disease
Author(s) -
Abraham Allistair A.,
Lang Haili,
Meier Emily Riehm,
Nickel Robert S.,
Dean Marcus,
Lawal Nurah,
SpellerBrown Barbara,
Wang Yunfei,
Kean Leslie,
Bollard Catherine M.
Publication year - 2019
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.27601
Subject(s) - nkg2d , cytotoxicity , medicine , cd16 , immunology , immunophenotyping , natural killer cell , k562 cells , degranulation , lymphokine activated killer cell , cell , interleukin 21 , flow cytometry , cd3 , receptor , immune system , cd8 , biology , in vitro , leukemia , biochemistry , genetics
Abstract Background Sickle cell disease (SCD) is increasingly recognized as a red blood cell disorder modulated by abnormally increased inflammation. We have previously shown that in patients with SCD not on a disease‐modifying therapy (hydroxyurea or chronic transfusions), natural killer (NK) cell numbers are increased. In the current study, we further investigated the NK cell function to determine if there was evidence of increased activation and cytotoxicity. Procedure We conducted a cross‐sectional study of 44 patients with HbSS/HbSβ 0 thalassemia at steady state (hydroxyurea = 13, chronic transfusion = 11, no disease‐modifying therapy = 20) and 23 healthy controls. Using a fresh blood sample, NK immunophenotyping was performed as follows: NK cells (CD3 − CD56 + lymphocytes) were evaluated for makers associated with activation (NKG2D, NKp30, NKp44, and CD69) and maturity (CD57, killer immunoglobulin‐like receptors (KIR), and CD56dim). Degranulation and cytotoxicity assays were performed to evaluate NK cell function. Results Patients with SCD who were not on disease‐modifying therapy had a higher number of NK cells with an immunophenotype associated with increased cytotoxicity (NKG2D + , NKp30 + , CD56dim + , and KIR + NK cells) compared with healthy controls and patients on hydroxyurea. NK cells from SCD patients not on disease‐modifying therapy demonstrated significantly increased cytotoxicity (measured by assaying NK cell killing of the K562 cell line) compared with healthy controls ( P = 0.005). Notably, NK cell cytotoxicity against K562 cells in the hydroxyurea or chronic transfusion patients was not significantly different from that in healthy controls. Conclusion SCD is associated with increased NK cell function as well as increased NK cell numbers, which appears to be normalized with disease‐modifying therapy.