Apolipoprotein A-I and serum amyloid a plasma levels are biomarkers of acute painful episodes in patients with sickle cell disease

Ashaunta Tumblin, Anitaben Tailor, Gerard T. Hoehn, A. Kyle Mack, Laurel Mendelsohn, Lita Freeman, Xiuli Xu, Alan T. Remaley, Peter J. Munson, Anthony F. Suffredini, Gregory J. Kato

Research output: Contribution to journalArticle

Abstract

Background Acute painful episodes are the clinical hallmark of sickle cell disease and have been linked to morbidity and mortality in the sickle cell population. Design and Methods We undertook exploratory proteomic studies on paired plasma samples collected from a cohort of 26 adult sickle cell patients during steady state and on the first day of an acute painful episode. We screened for changes in abundance of specific protein peaks via surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS), and confirmed the identify of candidate protein peaks by specific immunoassays. Results The levels of hemoglobin, hematocrit, total protein, and albumin were lower and the levels of lactate dehydrogenase and absolute reticulocytes higher during acute painful episodes than during the steady state. Surface-enhanced laser desorption/ionization time of flight mass spectrometry spectral analysis consistently showed a mass-to-charge peak at 11.7 kDa with elevated intensities during acute painful episodes, which correlated significantly with the serum amyloid A immunoassay. Serum amyloid A levels were significantly elevated during acute painful episodes, especially in four patients with marked end-organ complications of such episodes. A second, recurring peak, less abundant during acute painful episodes, was present at 28.1 kDa; this peak was correlated significantly with immunoassay measurements of apolipoprotein A1. Conclusions On the average, plasma serum amyloid A rises and apolipoprotein AI falls during acute painful episodes. The serum amyloid A/apolipoprotein AI ratio increased in 81% of the patients during acute painful episodes, potentially making it a useful objective marker of such episodes. We propose that these protein alterations, known to contribute to endothelial dysfunction in other settings, might do likewise acutely in acute painful episodes and present a new target for therapeutic intervention in sickle cell disease.

Original languageEnglish (US)
Pages (from-to)1467-1472
Number of pages6
JournalHaematologica
Volume95
Issue number9
DOIs
StatePublished - Sep 1 2010

Keywords

  • Acute painful episode
  • Immunoassay
  • Sickle cell disease

ASJC Scopus subject areas

  • Hematology

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    Tumblin, A., Tailor, A., Hoehn, G. T., Kyle Mack, A., Mendelsohn, L., Freeman, L., Xu, X., Remaley, A. T., Munson, P. J., Suffredini, A. F., & Kato, G. J. (2010). Apolipoprotein A-I and serum amyloid a plasma levels are biomarkers of acute painful episodes in patients with sickle cell disease. Haematologica, 95(9), 1467-1472. https://doi.org/10.3324/haematol.2009.018044