Immune dysregulation in sickle cell disease
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1
Michigan State University, United States
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2
University of Alabama at Birmingham, United States
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3
Cleveland Clinic, United States
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4
MetroHealth Medical Center, United States
Acute painful vaso-occlusive crises and recurrent infections are frequent complications of patients with sickle cell disease (SCD). Chronic activation of monocytes producing pro-inflammatory cytokines may play a role in immune dysregulation, susceptibility to infection, activation of vascular endothelium, and vaso-occlusion in SCD. The pathophysiology of SCD may be influenced by activated and/or immature monocytes. We compared activated monocytes in SCD with normal monocytes in healthy persons, analyzing CD4, CD14, CD16, and HLA-DR antigen expression using flow cytometry and morphologic assessment of monocytes with Wright and alpha-naphthyl butyrate esterase (ANBE) stains. SCD patients showed absolute monocytosis and decreased CD4+, CD4+HLA-DR+ and CD4+CD14+ monocyte expression and increased CD14(dim)+CD16+ expression. Monocytes in SCD showed immature morphology, including a high N/C ratio, indented nuclei, decreased cytoplasmic vacuolation and ANBE activity. We also examined the function of dendritic cells in SCD. Peripheral blood dendritic cells (PBDC) were purified from patients with SCD and from healthy donors. Monocyte-derived DC (MoDC) from patients and donors were generated in vitro with granulocyte/macrophage colony stimulating factor (GMCSF) and interleukin-(IL-)-4. Compared to healthy donors, PBDC from SCD patients showed reduced expression of HLA-DR, CD80, CD86, and CD40; reduced stimulatory capacity to mixed lymphocyte reactions; and reduced production of IL-12 in response to lipopolysaccharide and to CD40 ligand. Similar reductions were observed in MoDC from SCD patients. These results indicate that alterations in dendritic cell function are present in SCD patients. Alterations in both monocytes and dendritic cells in SCD may contribute to deficiencies in immune response and susceptibility to infection.
Keywords:
Sickle Cell Disease,
Dendritic Cells,
Monocytes,
Immunologic Factors,
Cytokines
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Immune-mediated disease pathogenesis
Citation:
Hrinczenko
B,
Mahtani
H,
Rodgers
H,
Cleveland
R,
Kass
L and
Triozzi
PL
(2013). Immune dysregulation in sickle cell disease.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.01044
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Received:
30 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Borys Hrinczenko, Michigan State University, East Lansing, Michigan, United States, Borys.Hrinczenko@hc.msu.edu