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. 2024 Aug 22;9(11):3318-3323.
doi: 10.1016/j.ekir.2024.08.014. eCollection 2024 Nov.

Exuberant Endothelial C5b-9 Formation in Recurrent and De Novo Posttransplant Thrombotic Microangiopathy

Sistiana Aiello  1 , Sara Gastoldi  1 , Elena Bresin  1 , Miriam Galbusera  1 , Caterina Mele  1 , Erica Daina  1 , Donata Santarsiero  1 , Giorgia Comai  2   3 , Gaetano La Manna  2   3 , Carolina Martinatto  1 , Ariela Benigni  1 , Giuseppe Remuzzi  1 , Marina Noris  1
Affiliations

Exuberant Endothelial C5b-9 Formation in Recurrent and De Novo Posttransplant Thrombotic Microangiopathy

Sistiana Aiello et al. Kidney Int Rep. .
No abstract available

Keywords: C5b-9; aHUS; complement; endothelial cells; kidney transplant.

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Figures

Figure 1
Figure 1
Ex-vivo serum-induced C5b-9 formation on endothelial cells. Human microvascular endothelial cells (HMEC-1), either unstimulated or preactivated for 10 minutes with adenosine diphosphate (ADP, 10 μmol/l) were incubated for 2 hours with serum (50% in test medium; details in Supplementary Material) from: panel a, aHUS kidney transplant (tx) patients with clinical and/or histologic signs of recurrence (yes: n = 13) and aHUS kidney transplant patients with stable graft function or with other causes of graft deterioration (no: n = 11), the colored circles indicate the 4 patients who were also studied while on chronic dialysis; panel (b), kidney transplant (tx) patients presenting with de novo TMA (n = 15) and renal transplant patients with stable graft function (n = 7); panel (c), kidney transplant patients with de novo TMA studied both before (pre) and after (post) initiation of eculizumab treatment (n = 2); panel (d), chronically dialyzed patients with a history of complement-related aHUS in the native kidneys (n = 28 on ADP-activated HMEC-1; n = 21 on unstimulated HMEC-1, 7 patients were not analyzed on unstimulated cells due to limited serum volume) and chronically dialyzed patients with other causes of end-stage renal disease (n = 11 both on ADP-activated and unstimulated HMEC-1), the colored circles indicate the 4 patients who were also studied after transplantation. Of note, 5 chronically dialyzed patients with aHUS showed elevated C5b-9 formation also on unstimulated HMEC-1; of these, 1 patient had multiple relapses, 1 patient had lost 2 grafts due to recurrences, and 1 patient had clinical signs of chronic aHUS. At the end of incubation, cells were washed, fixed, and stained with rabbit antihuman complement C5b-9 complex antibody, followed by FITC-conjugated secondary antibody. An Apotome Axio Imager Z2 (Zeiss) laser microscope was used to view the fluorescent staining on the endothelial cell surface, and the HMEC-1 area covered by C5b-9 staining was calculated using automatic edge detection (Image J software) in 15 high-power fields. For each sample, the highest and the lowest values were discarded and the mean of the other 13 fields was calculated, and values were expressed as the percentage of C5b-9 deposits induced by a pool of sera from 10 healthy controls run in parallel (reference 100%). Horizontal dashed lines are upper limit of the normal range (mean ± 2 SDs) of 35 (on ADP-activated HMEC-1) and 22 (on unstimulated HMEC-1) different healthy controls. FITC, fluorescein isothiocyanate; TMA, thrombotic microangiopathy.
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