title: Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis.
abstract: Intravenous immunoglobulin (IVIG) decreases neutrophil adhesion to endothelium and red blood cell-neutrophil interactions in sickle cell mice undergoing vaso-occlusion. In this Phase I clinical trial of sickle cell anemia (SCA) patients admitted with pain crisis, we evaluated the status of adhesion molecules on neutrophils in control and IVIG-treated subjects pre- and post-infusion up to 800 mg/kg, the same dose used in murine studies. Mac-1 function significantly decreased from baseline in the low-dose IVIG (200-400 mg/kg) cohorts. IVIG-related adverse events may have occurred in the high-dose (600-800 mg/kg) cohorts. There were no significant increases in neutrophil and leukocyte counts, suggesting that IVIG may more selectively inhibit Mac-1 function as opposed to neutrophil adhesion. This study provides the first in-human validation of pre-clinical murine studies that IVIG can decrease Mac-1 function.
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Deepa
authors.initials: D
authors.lastname: Manwani
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York
authors.forename: Grace
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Albert Einstein College of Medicine, Bronx, New York
authors.forename: Veronica
authors.initials: V
authors.lastname: Carullo
authors.affiliation: Department of Anesthesiology, Mount Sinai School of Medicine, New York, New York
authors.forename: Stelian
authors.initials: S
authors.lastname: Serban
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York
authors.forename: Olugbenga
authors.initials: O
authors.lastname: Olowokure
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York
authors.forename: Jungeun
authors.initials: J
authors.lastname: Jang
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York
authors.forename: Matthew
authors.initials: M
authors.lastname: Huggins
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York
authors.forename: Hillel W
authors.initials: HW
authors.lastname: Cohen
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York
authors.forename: Henny
authors.initials: H
authors.lastname: Billett
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York
authors.forename: George F
authors.initials: GF
authors.lastname: Atweh
authors.affiliation: Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York|Department of Medicine, Mount Sinai School of Medicine, New York, New York|Department of Medicine, Albert Einstein College of Medicine, Bronx, New York|Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, Bronx, New York
authors.forename: Paul S
authors.initials: PS
authors.lastname: Frenette
authors.affiliation: Department of Medicine, Mount Sinai School of Medicine, New York, New York|Department of Medicine, Albert Einstein College of Medicine, Bronx, New York|New York Blood Center, New York, New York
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Shi
mesh_terms: D056586:Acute Chest Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects; D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D016177:Macrophage-1 Antigen / Q000097:blood*; D008297:Male; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010146:Pain / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D016756:Immunoglobulins, Intravenous; D016177:Macrophage-1 Antigen