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Determinants of PF4/heparin immunogenicity.

Publication ,  Journal Article
Suvarna, S; Espinasse, B; Qi, R; Lubica, R; Poncz, M; Cines, DB; Wiesner, MR; Arepally, GM
Published in: Blood
December 15, 2007

Heparin-induced thrombocytopenia (HIT) is an antibody-mediated disorder that occurs with variable frequency in patients exposed to heparin. HIT antibodies preferentially recognize large macromolecular complexes formed between PF4 and heparin over a narrow range of molar ratios, but the biophysical properties of complexes that initiate antibody production are unknown. To identify structural determinants underlying PF4/heparin immunogenicity, we characterized the in vitro interactions of murine PF4 (mPF4) and heparin with respect to light absorption, size, and surface charge (zeta potential). We show that PF4/heparin macromolecular assembly occurs through colloidal interactions, wherein heparin facilitates the growth of complexes through charge neutralization. The size of PF4/heparin macromolecules is governed by the molar ratios of the reactants. Maximal complex size occurs at molar ratios of PF4/heparin at which surface charge is neutral. When mice are immunized with complexes that differ in size and/or zeta potential, antibody formation varies inversely with heparin concentration and is most robust in animals immunized with complexes displaying a net positive zeta-potential. These studies suggest that the clinical heterogeneity in the HIT immune response may be due in part to requirements for specific biophysical parameters of the PF4/heparin complexes that occur in settings of intense platelet activation and PF4 release.

Duke Scholars

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

December 15, 2007

Volume

110

Issue

13

Start / End Page

4253 / 4260

Location

United States

Related Subject Headings

  • Platelet Factor 4
  • Platelet Activation
  • Mice
  • Macromolecular Substances
  • Immunology
  • Heparin
  • Electrochemistry
  • Antibody Formation
  • Animals
  • 3213 Paediatrics
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Suvarna, S., Espinasse, B., Qi, R., Lubica, R., Poncz, M., Cines, D. B., … Arepally, G. M. (2007). Determinants of PF4/heparin immunogenicity. Blood, 110(13), 4253–4260. https://doi.org/10.1182/blood-2007-08-105098
Suvarna, Shayela, Benjamin Espinasse, Rui Qi, Rauova Lubica, Mortimer Poncz, Douglas B. Cines, Mark R. Wiesner, and Gowthami M. Arepally. “Determinants of PF4/heparin immunogenicity.Blood 110, no. 13 (December 15, 2007): 4253–60. https://doi.org/10.1182/blood-2007-08-105098.
Suvarna S, Espinasse B, Qi R, Lubica R, Poncz M, Cines DB, et al. Determinants of PF4/heparin immunogenicity. Blood. 2007 Dec 15;110(13):4253–60.
Suvarna, Shayela, et al. “Determinants of PF4/heparin immunogenicity.Blood, vol. 110, no. 13, Dec. 2007, pp. 4253–60. Pubmed, doi:10.1182/blood-2007-08-105098.
Suvarna S, Espinasse B, Qi R, Lubica R, Poncz M, Cines DB, Wiesner MR, Arepally GM. Determinants of PF4/heparin immunogenicity. Blood. 2007 Dec 15;110(13):4253–4260.

Published In

Blood

DOI

ISSN

0006-4971

Publication Date

December 15, 2007

Volume

110

Issue

13

Start / End Page

4253 / 4260

Location

United States

Related Subject Headings

  • Platelet Factor 4
  • Platelet Activation
  • Mice
  • Macromolecular Substances
  • Immunology
  • Heparin
  • Electrochemistry
  • Antibody Formation
  • Animals
  • 3213 Paediatrics