Sickle cell disease (SCD), iNKT cells, and regadenoson infusion.

David G. Nathan, Joshua Field, Gene Lin, Donna Neuberg, Elaine Majerus, Onyinye Onyekwere, Jeffrey Keefer, Maureen Okam, Ainsley Ross, Joel Linden

Research output: Contribution to journalArticle

Abstract

A humanized murine sickle cell-disease (SCD) model (NY1DD) has been used to study ischemia/reperfusion injury (IRI) in sickle cell anemia, and iNKT cells (a very small subset of murine and human T cells) have been found to instigate such injury in this model. Furthermore, levels of activated iNKT cells are generally elevated in the circulation of patients with SCD. Because activated iNKT cells are rich in adenosine A2A receptors which, when agonized, down-regulate the inflammatory cytokine expression that characterizes the cells, we have conducted a phase 1 trial of a constant infusion of low-dose regadenoson (an adenosine analogue with high A2A receptor specificity) to determine its safety and the capacity of a safe dose to down-regulate circulating iNKT cells in patients with SCD. We have found two dose rates that are both safe and effective and now plan a controlled Phase 2B clinical trial to determine whether our highest dose, administered as a 48-hour constant infusion, will induce faster remission in both painful vaso-occlusive crisis (pVOC) and acute chest syndrome (ACS).

Original languageEnglish (US)
JournalTransactions of the American Clinical and Climatological Association
Volume123
StatePublished - 2012
Externally publishedYes

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Natural Killer T-Cells
Sickle Cell Anemia
Down-Regulation
Acute Chest Syndrome
Adenosine A2A Receptors
Reperfusion Injury
Adenosine
Clinical Trials
Cytokines
T-Lymphocytes
Safety
regadenoson
Wounds and Injuries

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Nathan, D. G., Field, J., Lin, G., Neuberg, D., Majerus, E., Onyekwere, O., ... Linden, J. (2012). Sickle cell disease (SCD), iNKT cells, and regadenoson infusion. Transactions of the American Clinical and Climatological Association, 123.

Sickle cell disease (SCD), iNKT cells, and regadenoson infusion. / Nathan, David G.; Field, Joshua; Lin, Gene; Neuberg, Donna; Majerus, Elaine; Onyekwere, Onyinye; Keefer, Jeffrey; Okam, Maureen; Ross, Ainsley; Linden, Joel.

In: Transactions of the American Clinical and Climatological Association, Vol. 123, 2012.

Research output: Contribution to journalArticle

Nathan, DG, Field, J, Lin, G, Neuberg, D, Majerus, E, Onyekwere, O, Keefer, J, Okam, M, Ross, A & Linden, J 2012, 'Sickle cell disease (SCD), iNKT cells, and regadenoson infusion.', Transactions of the American Clinical and Climatological Association, vol. 123.
Nathan, David G. ; Field, Joshua ; Lin, Gene ; Neuberg, Donna ; Majerus, Elaine ; Onyekwere, Onyinye ; Keefer, Jeffrey ; Okam, Maureen ; Ross, Ainsley ; Linden, Joel. / Sickle cell disease (SCD), iNKT cells, and regadenoson infusion. In: Transactions of the American Clinical and Climatological Association. 2012 ; Vol. 123.
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