Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis

Deepa G. Manwani, Grace Chen, Veronica P. Carullo, Stelian Serban, Olugbenga Olowokure, Jungeun Jang, Matthew Huggins, Hillel W. Cohen, Henny H. Billett, George F. Atweh, Paul S. Frenette, Patricia A. Shi

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)381-385
Number of pages5
JournalAmerican Journal of Hematology
Volume90
Issue number5
DOIs
StatePublished - May 1 2015

Fingerprint

Intravenous Immunoglobulins
Neutrophils
Pain
Clinical Trials, Phase I
Sickle Cell Anemia
Leukocyte Count
Cell Communication
Endothelium
Erythrocytes

ASJC Scopus subject areas

  • Hematology

Cite this

Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis. / Manwani, Deepa G.; Chen, Grace; Carullo, Veronica P.; Serban, Stelian; Olowokure, Olugbenga; Jang, Jungeun; Huggins, Matthew; Cohen, Hillel W.; Billett, Henny H.; Atweh, George F.; Frenette, Paul S.; Shi, Patricia A.

In: American Journal of Hematology, Vol. 90, No. 5, 01.05.2015, p. 381-385.

Research output: Contribution to journalArticle

Manwani, DG, Chen, G, Carullo, VP, Serban, S, Olowokure, O, Jang, J, Huggins, M, Cohen, HW, Billett, HH, Atweh, GF, Frenette, PS & Shi, PA 2015, 'Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis', American Journal of Hematology, vol. 90, no. 5, pp. 381-385. https://doi.org/10.1002/ajh.23956
Manwani, Deepa G. ; Chen, Grace ; Carullo, Veronica P. ; Serban, Stelian ; Olowokure, Olugbenga ; Jang, Jungeun ; Huggins, Matthew ; Cohen, Hillel W. ; Billett, Henny H. ; Atweh, George F. ; Frenette, Paul S. ; Shi, Patricia A. / Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis. In: American Journal of Hematology. 2015 ; Vol. 90, No. 5. pp. 381-385.
@article{796e8df3a8e14bb68e24ca4d66a158a9,
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.",
author = "Manwani, {Deepa G.} and Grace Chen and Carullo, {Veronica P.} and Stelian Serban and Olugbenga Olowokure and Jungeun Jang and Matthew Huggins and Cohen, {Hillel W.} and Billett, {Henny H.} and Atweh, {George F.} and Frenette, {Paul S.} and Shi, {Patricia A.}",
year = "2015",
month = "5",
day = "1",
doi = "10.1002/ajh.23956",
language = "English (US)",
volume = "90",
pages = "381--385",
journal = "American Journal of Hematology",
issn = "0361-8609",
publisher = "Wiley-Liss Inc.",
number = "5",

}

TY - JOUR

T1 - Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis

AU - Manwani, Deepa G.

AU - Chen, Grace

AU - Carullo, Veronica P.

AU - Serban, Stelian

AU - Olowokure, Olugbenga

AU - Jang, Jungeun

AU - Huggins, Matthew

AU - Cohen, Hillel W.

AU - Billett, Henny H.

AU - Atweh, George F.

AU - Frenette, Paul S.

AU - Shi, Patricia A.

PY - 2015/5/1

Y1 - 2015/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84928285050&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928285050&partnerID=8YFLogxK

U2 - 10.1002/ajh.23956

DO - 10.1002/ajh.23956

M3 - Article

C2 - 25616042

AN - SCOPUS:84928285050

VL - 90

SP - 381

EP - 385

JO - American Journal of Hematology

JF - American Journal of Hematology

SN - 0361-8609

IS - 5

ER -