Thursday, July 3, 2014

Antibody-Mediated Rejection Despite Inhibition of Terminal Complement

Background : Terminal complement blockade has been shown to decrease the incidence of early acute antibody-mediated rejection (eAMR) in the first month after positive crossmatch kidney transplant recipients, yet some patients still develop eAMR.
Methods : The current study investigated possible mechanisms of eAMR despite eculizumab treatment. Of the 26 patients treated with eculizumab, 2 developed clinical eAMR and another patient developed histologic signs of eAMR without graft dysfunction (“subclinical eAMR”). Twenty three did not have histologic injury on early surveillance biopsies.
Results : All 26 patients had therapeutic levels of eculizumab and showed complete blockade of complement in hemolytic assays. High levels of donor-specific alloantibody (DSA) including total IgG, IgG3 and C1q+ DSA were present in patients with and without eAMR and none correlated well with eAMR. In contrast, IgM DSA was present in only 4 patients after transplantation: the 2 patients with clinical eAMR, 1 patient with subclinical AMR and 1 patient without eAMR (p=0.006 correlation with eAMR). Both clinical eAMR episodes were easily treated with plasma exchange which removed IgM more completely and rapidly than IgG, resulting in normalization of function and histology.
Conclusion : These data suggest a possible role of anti-donor IgM DSA in the pathogenesis of eAMR in patients treated with terminal complement blockade (read more) Print this post

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