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Oxygen removal during pathogen inactivation with riboflavin and UV light preserves protein function in plasma for transfusion

(2014) VOX SANGUINIS. 106(4). p.307-315
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Abstract
Background and Objective : Photochemical pathogen inactivation technologies (PCT) for individual transfusion products act by inhibition of replication through irreversibly damaging nucleic acids. Concern on the collateral impact of PCT on the blood component's integrity has caused reluctance to introduce this technology in routine practice. This work aims to uncover the mechanism of damage to plasma constituents by riboflavin pathogen reduction technology (RF-PRT). Methods : Activity and antigen of plasma components were determined following RF-PRT in the presence or absence of dissolved molecular oxygen. Results : Employing ADAMTS13 as a sentinel molecule in plasma, our data show that its activity and antigen are reduced by 23 +/- 8% and 29 +/- 9% (n=24), respectively, which corroborates with a mean decrease of 25% observed for other coagulation factors. Western blotting of ADAMTS13 shows decreased molecular integrity, with no obvious indication of additional proteolysis nor is riboflavin able to directly inhibit the enzyme. However, physical removal of dissolved oxygen prior to RF-PRT protects ADAMTS13 as well as FVIII and fibrinogen from damage, indicating a direct role for reactive oxygen species. Redox dye measurements indicate that superoxide anions are specifically generated during RF-PRT. Protein carbonyl content as a marker of disseminated irreversible biomolecular damage was significantly increased (3 center dot 1 +/- 0 center dot 8 vs. 1 center dot 6 +/- 0 center dot 5nmol/mg protein) following RF-PRT, but not in the absence of dissolved molecular oxygen (1 center dot 8 +/- 0 center dot 4nmol/mg). Conclusions : RF-PRT of single plasma units generates reactive oxygen species that adversely affect biomolecular integrity of relevant plasma constituents, a side-effect, which can be bypassed by applying hypoxic conditions during the pathogen inactivation process.
Keywords
reactive oxygen species, plasma, pathogen inactivation, THROMBOTIC THROMBOCYTOPENIC PURPURA, FRESH-FROZEN PLASMA, REDUCTION, SUPEROXIDE, PHOTOCHEMICAL INACTIVATION, BACTERIA, ADAMTS13, SINGLET OXYGEN, CARBONYL GROUPS, DNA

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Citation

Please use this url to cite or link to this publication:

Chicago
Feys, Hendrik, Britt Van Aelst, Katrien Devreese, Rosalie Devloo, J Coene, Philippe Vandekerckhove, and Veerle Compernolle. 2014. “Oxygen Removal During Pathogen Inactivation with Riboflavin and UV Light Preserves Protein Function in Plasma for Transfusion.” Vox Sanguinis 106 (4): 307–315.
APA
Feys, Hendrik, Van Aelst, B., Devreese, K., Devloo, R., Coene, J., Vandekerckhove, P., & Compernolle, V. (2014). Oxygen removal during pathogen inactivation with riboflavin and UV light preserves protein function in plasma for transfusion. VOX SANGUINIS, 106(4), 307–315.
Vancouver
1.
Feys H, Van Aelst B, Devreese K, Devloo R, Coene J, Vandekerckhove P, et al. Oxygen removal during pathogen inactivation with riboflavin and UV light preserves protein function in plasma for transfusion. VOX SANGUINIS. 2014;106(4):307–15.
MLA
Feys, Hendrik, Britt Van Aelst, Katrien Devreese, et al. “Oxygen Removal During Pathogen Inactivation with Riboflavin and UV Light Preserves Protein Function in Plasma for Transfusion.” VOX SANGUINIS 106.4 (2014): 307–315. Print.
@article{5643967,
  abstract     = {Background and Objective : Photochemical pathogen inactivation technologies (PCT) for individual transfusion products act by inhibition of replication through irreversibly damaging nucleic acids. Concern on the collateral impact of PCT on the blood component's integrity has caused reluctance to introduce this technology in routine practice. This work aims to uncover the mechanism of damage to plasma constituents by riboflavin pathogen reduction technology (RF-PRT).
Methods : Activity and antigen of plasma components were determined following RF-PRT in the presence or absence of dissolved molecular oxygen.
Results : Employing ADAMTS13 as a sentinel molecule in plasma, our data show that its activity and antigen are reduced by 23 +/- 8\% and 29 +/- 9\% (n=24), respectively, which corroborates with a mean decrease of 25\% observed for other coagulation factors. Western blotting of ADAMTS13 shows decreased molecular integrity, with no obvious indication of additional proteolysis nor is riboflavin able to directly inhibit the enzyme. However, physical removal of dissolved oxygen prior to RF-PRT protects ADAMTS13 as well as FVIII and fibrinogen from damage, indicating a direct role for reactive oxygen species. Redox dye measurements indicate that superoxide anions are specifically generated during RF-PRT. Protein carbonyl content as a marker of disseminated irreversible biomolecular damage was significantly increased (3 center dot 1 +/- 0 center dot 8 vs. 1 center dot 6 +/- 0 center dot 5nmol/mg protein) following RF-PRT, but not in the absence of dissolved molecular oxygen (1 center dot 8 +/- 0 center dot 4nmol/mg).
Conclusions : RF-PRT of single plasma units generates reactive oxygen species that adversely affect biomolecular integrity of relevant plasma constituents, a side-effect, which can be bypassed by applying hypoxic conditions during the pathogen inactivation process.},
  author       = {Feys, Hendrik and Van Aelst, Britt and Devreese, Katrien and Devloo, Rosalie and Coene, J and Vandekerckhove, Philippe and Compernolle, Veerle},
  issn         = {0042-9007},
  journal      = {VOX SANGUINIS},
  language     = {eng},
  number       = {4},
  pages        = {307--315},
  title        = {Oxygen removal during pathogen inactivation with riboflavin and UV light preserves protein function in plasma for transfusion},
  url          = {http://dx.doi.org/10.1111/vox.12106},
  volume       = {106},
  year         = {2014},
}

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