De Novo Donor-Specific Antibody at the Time of Kidney Transplant Biopsy Associates with Microvascular Pathology and Late Graft Failure

Abstract

We studied whether de novo donor-specific antibodies (DSA) in sera from patients undergoing kidney transplant biopsies associate with specific histologic lesions in the biopsy and prognosis. DSA were assessed in 145 patients at the time of biopsy between 7 days to 31 years posttransplant. DSA was detected in 54 patients (37%), of which 32 represented de novo DSA. De novo DSA was more frequent in patients having late biopsies (34%) versus early biopsies (4%), and was usually either against class II alone or class I and II but rarely against class I alone. Microcirculation inflammation (glomerulitis, capillaritis) and damage (glomuerulopathy, capillary basement membrane multilayering), and C4d staining were associated with de novo DSA. However, the degree of scarring, arterial fibrosis and tubulo-interstitial inflammation did not correlate with the presence of de novo DSA. De novo DSA correlated with reduced graft survival after the biopsy. Thus, de novo DSA at the time of a late biopsy for clinical indication is primarily against class II, and associates with microcirculation changes in the biopsy and subsequent graft failure. We propose careful assessment of de novo DSA, particularly against class II, be performed in all late kidney transplant biopsies.

MICA Variant Promotes Allosensitization after Kidney Transplantation

“…The role of NK cells in transplant immunology has probably been underestimated, and the contribution of NK cells to graft rejection is an emerging concept supported by recent studies. [33][34][35] Our findings support the importance of endothelial expression of polymorphic MICA molecules and of possible mismatch between NK receptors and ligands expressed on recipients and donors, respectively.…”

Glomerular damage as a predictor of renal allograft loss

“…This finding agrees with recently published studies (25)(26)(27)(28)(29). Wavamunno et al (30) showed that endothelial and subendothelial ultrastructural abnormalities in glomerular and peritubular capillaries are sensitive early markers of CTG.…”

Comparison of the Treatment Efficacy of Rituximab and Plasmapheresis/Intravenous Immunoglobulin Combination with Historical Control in Chronic Antibody Mediated Rejection

“…De-novo or pre-existing donor specific, especially Class II HLA antibodies have proven to be responsible for the late immune response and chronic antibody mediated injury that leads to graft failure (8,(15)(16)(17)(18)(19). In harmony with these data, we found that all of our recipients had flow cytometric panel reactive test positive, particularly for anti-HLA Class II antibody and seven of the nine patients had donor specific Class II antibody.…”