title: High multi-cytokine levels are not a predictive marker of alloimmunization in transfused sickle cell disease patients.
abstract: Patients with sickle cell disease (SCD) receive multiple red blood cell (RBC) transfusions for both prevention of and therapy for disease-related complications. In some patients, transfusion results in development of both allo- and auto-antibodies to RBC antigens. What precipitates the antibody formation is currently unclear. It has been hypothesized that a pro-inflammatory state preceding the therapeutic transfusion may be a predisposing factor. Plasma levels of ten cytokines were evaluated upon recruitment to the study of 83 children with SCD undergoing therapeutic RBC transfusions. The levels of cytokines were correlated with development of anti-RBC antibodies prior, or during seven years post recruitment. Twelve subjects displayed significantly higher levels of all cytokines examined, with pro-, as well as anti-inflammatory properties. Surprisingly, the elevated levels of cytokines were preferentially found in patients without anti-RBC allo- and/or auto-antibodies. Further, presence of high cytokine levels was not predictive of anti-RBC antibody development during the subsequent seven year follow up. These data suggest that the increased concentration of multiple cytokines is not a biomarker of either the presence of or susceptibility to the development of RBC alloimmunization.
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC, United States; Department of Pediatrics, George Washington University School of Medicine, Washington, DC, United States.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Tatari-Calderone
authors.affiliation: Department of Pediatrics, George Washington University School of Medicine, Washington, DC, United States; Division of Hematology and Oncology, Children's National Medical Center, Washington, DC, United States; Division of Laboratory Medicine, Children's National Medical Center, Washington, DC, United States.
authors.forename: Ross M
authors.initials: RM
authors.lastname: Fasano
authors.affiliation: Division of Laboratory Medicine, Children's National Medical Center, Washington, DC, United States.
authors.forename: Megan R
authors.initials: MR
authors.lastname: Miles
authors.affiliation: HPV Immunology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, United States.
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
authors.affiliation: Department of Pediatrics, George Washington University School of Medicine, Washington, DC, United States; Division of Hematology and Oncology, Children's National Medical Center, Washington, DC, United States; Division of Laboratory Medicine, Children's National Medical Center, Washington, DC, United States.
authors.forename: Naomi L C
authors.initials: NL
authors.lastname: Luban
authors.affiliation: Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC, United States; Department of Pediatrics, George Washington University School of Medicine, Washington, DC, United States. Electronic address: svukmano@childrensnational.org.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Vukmanovic
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood* / Q000276:immunology / Q000628:therapy; D015415:Biomarkers / Q000097:blood*; D002648:Child; D016207:Cytokines / Q000097:blood*; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000276:immunology; D006801:Humans
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: Antibodies; Cytokines; Inflammation; Red blood cell transfusion; Sickle cell disease