Alloantibody Levels and Capillary Endothelial Ultrastructural Features in Positive Crossmatch (+XM) Kidney Allografts
LD Cornell, JM Burns, MD Stegall. Mayo Clinic, Rochester, MN
Background: Glomerular and peritubular capillary endothelial cells show reactive changes in acute humoral rejection (AHR). We sought to determine whether antibody-mediated injury, as detected by electron microscopy (EM), correlates with alloantibody levels in +XM kidney allografts.
Design: A retrospective review was performed of consecutive +XM, ABO-compatible allografts during a two-year period. Protocol and indication biopsies with EM and serologic data from the time of biopsy were reviewed. EMs were reviewed without knowledge of antibody status and were categorized into groups, based on the presence (>25% of area) of reactive-appearing endothelial cells (REC) in glomerular (Glom) and peritubular capillaries (PTC). Corresponding donor-specific antibody (DSA) measurements by T and B cell flow crossmatch (FXM) and single-antigen beads for HLA class I and II (SAB-DSA-I, -II) were reported as mean fluorescence channel shift and as the mean fluorescence index (MFI), respectively. AHR was defined as C4d positivity with histologic evidence of acute tissue injury.
Results: Forty-one biopsies from 33 patients had electron microscopy performed and had serum DSA measurements near the time of biopsy. The mean time of biopsy post-transplant was 2.8 mos (range, 0-18). Most cases showed normal glomerular and PTC endothelial cells. Features of RECs included cell enlargement, loss of fenestrations, and cytoplasmic protrusions. The Glom and PTC REC groups showed higher T- and B-FXM channel shifts, higher MFI for SAB-DSA-I and -II, and a higher percentage of C4d positivity and AHR compared to the groups with normal endothelium.
EM Capillary Reactivity and Serum DSA LevelsFXM and SAB expressed as mean (std dev)
|Group||T-FXM||B-FXM||SAB-DSA I||SAB-DSA II||% C4d positive||% AHR|
|Glom-Normal (n=21)||111 (+/-140), n=16||160 (+/-138), n=16||1014 (+/-2090), n=13||3315 (+/-4289), n=13||5%||0%|
|Glom-REC (n=19)||236 (+/-148), n=12||356 (+/-133), n=12||5071 (+/-4748), n=14||6846 (+/-5504), n=14||70%||53%|
|PTC-Normal (n=25)||115 (+/-168), n=21||220 (+/-177), n=21||3080 (+/-4548), n=19||4218 (+/-4658), n=19||24%||8%|
|PTC-REC (n=16)||259 (+/-118), n=10||356 (+/-129), n=10||4502 (+/-3686), n=12||8032 (+/-5156), n=12||69%||50%|
Conclusions: The presence RECs in glomeruli and PTCs correlates with the serum level of DSA, and with C4d positivity and AHR. These findings may be useful in evaluating the effectiveness of new complement-inhibitory drugs that block complement at the level of the endothelium but do not affect serum DSA levels.
Category: Kidney (does not include tumors)
Monday, March 9, 2009 9:00 AM
Platform Session: Section G 1, Monday Morning