Several studies have highlighted the low sensitivity of C4d immunohistochemistry
for the diagnosis of AMR in lung and other grafts (1,2); the addition of novel
biomarkers of capillary inflammation and endothelial injury could therefore increase
sensitivity of the diagnosis. Thus, novel immunohistochemical (see section “Immunohistochemistry”)
and molecular biomarkers are under investigation. The majority of preliminary
studies have been performed in kidney or heart transplantation. Sellares et al (3)
concluded that changes in AMR-associated gene expression (mostly in endothelial or NK cells)
correlated with the presence of capillary lesions or DSA and may be a good predictor of graft
failure independent of C4d staining. Expression of endothelial activation and injury transcripts
in biopsies has been proposed by Hildago et al and Sis et al (4,5) as new markers to better
understand the pathogenesis of AMR. Moreover, these markers could also be useful to predict
graft outcomes and define AMR even in C4d-negative kidney biopsies of recipients with elevated
levels of antibodies.
Fiorella Calabrese (Pathologist, University Hospital of Padua, Italy)
References :
1. Wallace WD, Li N, Andersen CB, Arrossi AV, Askar M, Berry GJ, DeNicola MM, Neil DA, Pavlisko EN, Reed EF, Remmelink M, Sam Weigt S, Weynand B, Zhang JQ, Budev MM, Farver CF. Banff study of pathologic changes in lung allograft biopsy specimens with donor-specific antibodies. J Heart Lung Transplant. 2016;35(1):40-8.
2. Djamali A, Kaufman DB, Ellis TM, Zhong W, Matas A, Samaniego M. Diagnosis and management of antibody-mediated rejection: current status and novel approaches. Am J Transplant.2014; 14(2):255-71.
3. Sellarés J, Reeve J, Loupy A, Mengel M, Sis B, Skene A, de Freitas DG, Kreepala C, Hidalgo LG, Famulski KS, Halloran PF. Molecular diagnosis of antibody-mediated rejection in human kidney transplants. Am J Transplant. 2013;13(4):971-83.
4. Hidalgo LG, Sis B, Sellares J, Campbell PM, Mengel M, Einecke G, Chang J, Halloran PF. NK cell transcripts and NK cells in kidney biopsies from patients with donor-specific antibodies: evidence for NK cell involvement in antibody-mediated rejection. Am J Transplant. 2010;10(8):1812-22.
5. Sis B, Jhangri GS, Bunnag S, Allanach K, Kaplan B, Halloran PF. Endothelial gene expression in kidney transplants with alloantibody indicates antibody-mediated damage despite lack of C4d staining. Am J Transplant.2009;9(10):2312-23.
