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Am J Transplant. 2010 Mar;10(3):510-7. doi: 10.1111/j.1600-6143.2009.02958.x. Epub 2010 Jan 5.

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

Author information

1
Transplantation Division, Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, MA, USA.

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.

PMID:
20055805
PMCID:
PMC3252386
DOI:
10.1111/j.1600-6143.2009.02958.x
[Indexed for MEDLINE]
Free PMC Article

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