Complement independent antibody-mediated endarteritis and transplant arteriopathy in mice.

Abstract

Complement fixation, as evidenced by C4d in the microvasculature, is a widely accepted criterion of antibody-mediated rejection. Complement fixation has been shown to be essential in acute antibody-mediated rejection, but its role in chronic rejection has not been addressed. Previous studies showed that passive transfer of complement fixing monoclonal IgG2a anti-H-2Kk into B6.RAG1-/- KO recipients of B10.BR hearts led to progressive chronic transplant arteriopathy (CTA) over 14-28 days, accompanied by C4d deposition. The present studies were designed to test whether complement was required for these lesions. We report that a noncomplement fixing donor-specific alloantibody (DSA, monoclonal IgG1 anti-H-2Kk) injected into B6.RAG1-/- KO recipients of B10.BR hearts also promotes CTA, without C4d deposition. Furthermore, a passive transfer of DSA (monoclonal IgG2a anti-H-2Kk) initiated endarteritis followed by CTA in B6.RAG1-/- mice genetically deficient in the third component of complement (RAG1-/-C3-/-). These studies indicate that antibody to class I MHC antigens can trigger chronic arterial lesions in vivo without complement participation, in contrast to acute antibody-mediated rejection. This pathway may be relevant to C4d-negative chronic rejection sometimes observed in patients with DSA, and argues that lack of C4d deposition does not exclude antibody-mediated chronic rejection.

• Authors: T Hirohashi, S Uehara, C M Chase, P DellaPelle, J C Madsen, P S Russell, R B Colvin
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 10 Issue 3 Pg. 510-7 (Mar 2010) ISSN: 1600-6143 [Electronic] United States
• PMID: 20055805 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Antibodies, Monoclonal
• Peptide Fragments
• Complement C4b
• complement C4d
• Complement System Proteins

Topics

• Animals
• Antibodies (chemistry)
• Antibodies, Monoclonal (metabolism)
• Arteries (pathology)
• Complement C4b (genetics)
• Complement System Proteins (metabolism)
• Disease Progression
• Endarteritis (immunology)
• Heart (physiology)
• Heart Transplantation (methods)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Peptide Fragments (genetics)
• Time Factors