Clinical and Molecular Significance of Microvascular Inflammation Negative Transplant Glomerulopathy.

M. Lubetzky,¹ N. Hayde,¹ P. O Broin,² Y. Bao,¹ E. Akalin.¹

¹Montefiore Medical Center, Bronx
²National University of Ireland Galway University, Galaway, Ireland

Meeting: 2017 American Transplant Congress

Abstract number: B59

Keywords: Gene expression, Graft survival, Rejection

Session Information

Session Name: Poster Session B: Antibody Mediated Rejection in Kidney Transplant Recipients II

Session Type: Poster Session

Date: Sunday, April 30, 2017

Session Time: 6:00pm-7:00pm

Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Transplant glomerulopathy (TGP) with donor specific antibodies (DSA) and microvascular inflammation (MVI) is due to chronic antibody mediated rejection (CAMR). We reported previously that intragraft gene profiles of DSA negative (DSA-)TGP is different than DSA+ TGP, however, some DSA+ TGP do not have MVI and some DSA- TGP have MVI. We aimed to assess whether clinical outcomes and genomics of MVI negative (MVI-neg) TGP is different than MVI positive (MVI-pos) TGP.

For-cause kidney biopsies from 2009 to 2014 were reviewed and 100 TGP cases were identified. TGP was classified as MVI-pos, g+ptc ≥2, or MVI-neg, g+ptc<2. 44 patients had biopsy samples for gene profiling; 17 MVI-pos TGP, 15 MVI-neg TGP, and 12 normal. Subgroup analysis of 10 MVI-neg, DSA- biopsies was compared to 5 MVI-neg, DSA+ biopsies.

There was no difference in terms of sex, race or type of transplant between the MVI-pos (n=51) and MVI-neg groups (n=49). More MVI-pos TGP had graft loss when compared to MVI-neg (64.7% versus 55.1%), but this was not significant (p=0.40). There was no difference in graft survival in the MVI-neg group patients who were DSA+ compared to DSA- (p=0.81). Pathogenesis based transcripts revealed increased expression of gamma interferon and rejection (GRIT) and DSA associated transcripts (DSAST) when MVI-pos TGP was compared to normal. When MVI-neg TGP was compared to normal, increased expression of Cytotoxic T cell (CAT), T-regulatory cell (TREG), and B cell associated transcripts (BAT) were observed but not GRIT or DSAST. There was no difference in gene expression of MVI-neg with or without DSA.

Gene expression profiles of TGP in the absence of MVI involve an upregulation of cellular immune responses distinct from CAMR and that is irrespective of the presence of DSA. Clinically, the prognosis of TGP remains poor even in the absence of MVI and DSA.

Pathogenesis Based Transcripts	MVI-pos TGP vs normal	MVI-neg TGP vs normal	MVI-neg/DSA- vs normal	MVI-neg/DSA+ vs MVI-neg/DSA-
GRIT	0.02	0.08	0.07	0.31
CAT	0.002	0.014	0.016	0.26
TREG	0.01	0.02	0.014	0.30
BAT	0.11	0.04	0.05	0.45
NKAT	0.17	0.19	0.26	0.31
CMAT	0.02	0.08	0.04	0.66
DSAST	0.009	0.13	0.39	0.08
ENDAT	0.31	0.42	0.38	0.56

CITATION INFORMATION: Lubetzky M, Hayde N, O Broin P, Bao Y, Akalin E. Clinical and Molecular Significance of Microvascular Inflammation Negative Transplant Glomerulopathy. Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Lubetzky M, Hayde N, Broin PO, Bao Y, Akalin E. Clinical and Molecular Significance of Microvascular Inflammation Negative Transplant Glomerulopathy. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/clinical-and-molecular-significance-of-microvascular-inflammation-negative-transplant-glomerulopathy/. Accessed November 22, 2024.

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