Evaluation of potential immune response and in vivo survival of riboflavin-ultraviolet light–treated red blood cells in baboons

Authors

  • Raymond P. Goodrich,

    1. From Navigant Biotechnologies, Lakewood, Colorado; the Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas; and the Research Department, American Red Cross Blood Services Southern California Region, Pomona, California.
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  • Krishna K. Murthy,

    1. From Navigant Biotechnologies, Lakewood, Colorado; the Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas; and the Research Department, American Red Cross Blood Services Southern California Region, Pomona, California.
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  • Suzann K. Doane,

    1. From Navigant Biotechnologies, Lakewood, Colorado; the Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas; and the Research Department, American Red Cross Blood Services Southern California Region, Pomona, California.
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  • Christy N. Fitzpatrick,

    1. From Navigant Biotechnologies, Lakewood, Colorado; the Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas; and the Research Department, American Red Cross Blood Services Southern California Region, Pomona, California.
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  • La Shayla Morrow,

    1. From Navigant Biotechnologies, Lakewood, Colorado; the Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas; and the Research Department, American Red Cross Blood Services Southern California Region, Pomona, California.
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  • Patricia A. Arndt,

    1. From Navigant Biotechnologies, Lakewood, Colorado; the Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas; and the Research Department, American Red Cross Blood Services Southern California Region, Pomona, California.
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  • Heather L. Reddy,

    1. From Navigant Biotechnologies, Lakewood, Colorado; the Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas; and the Research Department, American Red Cross Blood Services Southern California Region, Pomona, California.
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  • Kimberley A. Buytaert-Hoefen,

    1. From Navigant Biotechnologies, Lakewood, Colorado; the Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas; and the Research Department, American Red Cross Blood Services Southern California Region, Pomona, California.
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  • George Garratty

    1. From Navigant Biotechnologies, Lakewood, Colorado; the Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas; and the Research Department, American Red Cross Blood Services Southern California Region, Pomona, California.
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  • Supported by a grant from the Department of Defense, Contract W81XWH-05-2-0001. This work was supported by a Defense Appropriations Bill for applications to improve the safety and availability of transfused blood for the US Armed Forces. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of Defense.

  • Disclosures: RG, SD, CF, KBH, and HR were employees of Navigant Biotechnologies during the course of the study. KKM is a consultant for Navigant Biotechnologies. GG is a consultant for Navigant Biotechnologies.

Raymond P. Goodrich, PhD, Chief Science Officer, Navigant Biotechnologies, LLC, 1215 Quail Street, Lakewood, CO 80227; e-mail: ray.goodrich@navigantbiotech.com.

Abstract

BACKGROUND: Pathogen reduction methods have the potential to modify blood components, resulting in immunologic reactions or compromised blood components. This study evaluated the hypothesis that there is no immune response to riboflavin-and-ultraviolet [UV]-light–treated red blood cells (RBCs), as observed by serology and by survival of RBCs in circulation.

STUDY DESIGN AND METHODS: Three baboons were in each treatment group: 1) untreated (negative control), 2) quinacrine mustard (QM)-treated (positive control), and 3) riboflavin-and-UV light–treated (test group) RBCs. In the immunization phase, autologous test or control RBCs were injected subcutaneously on Days 0, 21, 42, and 49. Plasma samples from these days were tested against test or control RBCs by flow cytometry and standard serology. On Day 56, autologous 51Cr-labeled test or control RBCs were injected. Blood samples were taken over 21 days after injection to determine RBC survival (t1/2).

RESULTS: Untreated and riboflavin-and-UV-light–treated RBCs showed no evidence of significant immunoglobulin G (IgG) binding after incubation with autologous plasma. RBC-bound IgG was detected on QM-treated RBCs after incubation with autologous plasma. This antibody was inhibited by QM, as demonstrated by a hapten inhibition study. t1/2 values for the untreated and riboflavin-and-UV-light–treated RBCs were 7.3 ± 0.8 and 7.5 ± 1.7 days, respectively; the t1/2 value for QM-treated RBCs was 2.3 ± 2.9 days.

CONCLUSION: Treatment with riboflavin and UV light did not render RBCs immunogenic. Positive controls indicated that immunization promoted an immune response. In the 51Cr-labeled RBC survival phase of the study, riboflavin-and-UV-light–treated RBCs exhibited behavior similar to negative control RBCs. Detrimental immunologic or functional side effects were not observed.

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