1305. Antibody and Complement Depletion Ameliorate Murine Cytomegalovirus Accelerated Renal Allograft Damage
Session: Poster Abstract Session: Viral Immunology and Pathogenesis
Saturday, October 22, 2011
Room: Poster Hall B1
Background: Human cytomegalovirus (HCMV) infection remains a serious complication in solid organ transplantation and has been associated with poor renal allograft outcome in seroepidemiologic studies. However, the pathogenesis of HCMV mediated allograft damage has not been fully defined.
Methods: A murine model for cytomegalovirus in renal transplantation was used, in which murine CMV (MCMV) infected BALB/c donor organs were transplanted into uninfected C57BL/6 wildtype or antibody deficient C57BL/6-Igh-6tm1Cgn (Ig-KO) recipients without the removal of the contralateral native kidney or the need for immunosuppression. MCMV-specific or control serum was given to Ig-KO recipients to assess the role of anti-MCMV antibodies on allograft damage. In independent studies, complement was depleted in MCMV recipients via cobra venom factor 1, to determine the involvement of intragraft complement activation in graft injury.
Results: Allograft histology 14 days post transplantation demonstrated that MCMV infected allografts (MCMV) exhibit accelerated damage compared to uninfected allografts (Mock), associated with intragraft IgG antibody deposition and complement C3 fixation as early as 3 days post transplantation. Flow cytometry analyses showed that MCMV allografts contain significantly less cellular immune infiltrates compared to Mock grafts at 14 days post transplantation. Despite the presence of MCMV in the contralateral native kidneys, histology of the MCMV native kidneys remained normal with no significant immune infiltrates, antibody deposition or C3 fixation. Histology of Ig-KO allografts showed reduced graft damage compared to the MCMV allografts. Passive transfer of MCMV antiserum, but not control serum, into Ig-KO recipients restores intragraft IgG antibody deposition and C3 fixation. Consistent with this result, histology of allografts from complement depleted MCMV recipients demonstrated less graft injury despite intragraft antibody deposition.
Conclusion: These results suggest that MCMV accelerated renal allograft damage is associated with intragraft MCMV-specific IgG antibody deposition leading to complement activation, and that the allogeneic response is required for enhanced MCMV associated allograft damage.

Subject Category: V. Virology including clinical and basic studies of viral infections, including hepatitis

Ute Saunders, Ph.D.1, Lingling Guo, M.D.2, James F. George, Ph.D.2, Trenton Schoeb, DVM/PhD3, William J. Britt, M.D.1 and Masako Shimamura, MD4, (1)Pediatric Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL, (2)Cardiovascular/Thoracic Surgery, University of Alabama at Birmingham, Birmingham, AL, (3)Genetic Research Division, University of Alabama at Birmingham, Birmingham, AL, (4)Pediatrics, Division of Infectious Diseases, University of Alabama at Birmingham, Birmingham, AL

Disclosures:

U. Saunders, None

L. Guo, None

J. F. George, None

T. Schoeb, None

W. J. Britt, None

M. Shimamura, None

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