The Impact of Therapy On the Inflammatory Infiltrate in Renal Allografts With Acute and Chronic Antibody Mediated Rejection

W. Mulley,^1,2 D. Nikolic-Paterson,^1,2 A. Longano,³ Y. Han,¹ F. Ma,¹ J. Kanellis,^1,2 S. Ramessur.^1,2

¹Department of Nephrology, Monash Health, Clayton, Vic, Australia
²Department of Medicine, Monash University, Clayton, Vic, Australia
³Department of Pathology, Monash Health, Clayton, Vic, Australia.

Meeting: 2015 American Transplant Congress

Abstract number: A113

Keywords: Antibodies, Biopsy, IVIG

Session Information

Session Name: Poster Session A: Kidney Antibody Mediated Rejection

Session Type: Poster Session

Date: Saturday, May 2, 2015

Session Time: 5:30pm-7:30pm

Presentation Time: 5:30pm-7:30pm

Location: Exhibit Hall E

Little is known about the effect of usual treatment for acute and chronic antibody mediated rejection (aAMR and cAMR) on inflammatory cells within the allograft. We studied patients treated with common regimens for refractory aAMR (n=8) and cAMR (n=8) with sufficient biopsy tissue for further staining. Treatment for aAMR was 2-4 weeks plasma exchange/low dose IVIg (PEx/IVIg) then 500mg rituximab +/- high dose IVIg (HDIVIg). Treatment of cAMR was HDIVIg then 500mg rituximab +/- further HDIVIg. Biopsies at diagnosis and after treatment were stained for macrophages (M0), neutrophils (N0), T and B-cells. Interstitial and glomerular cells were counted. Ranks were compared by paired non-parametric tests. Median days from transplant to diagnosis were 9 (aAMR) and 728 (cAMR). Median GFR at diagnosis (28.6ml/min (aAMR) and 36.4ml/min (cAMR)). All patients except one had DSA at diagnosis. In aAMR, PEX/IVIg was associated with a 3-fold increase in interstitial T-cells (p=0.036) and 86% increase in M0 (p=0.05). B-cells increased by 50% whilst N0 were 4 fold less numerous however p=ns. There was no significant change in glomerular cell numbers. After rituximab, B-cells were eliminated, there were 90% less N0 than at diagnosis (p=0.02) in interstitium and glomeruli and interstitial M0 were less than at diagnosis and after PEX/IVIg (p=0.05). Other cell types showed no significant change. cAMR biopsies had more T and B-cells relative to aAMR but fewer N0 and M0. After HDIVIg the median interstitial M0 count doubled (p=0.025) with no change in interstitial or glomerular N0, B or T-cells. Rituximab eliminated B-cells from allografts but had little impact on other cells. The fall in N0 with aAMR treatment may be due to antibody removal or a shift to chronic inflammation. The M0 increase with PEx/IVIg (aAMR) and HDIVIg (cAMR) may be due to resistance to therapy or alternatively an influx of reparative M0. T-cells increased with PEX/IVIg in aAMR but were not significantly affected by rituximab or HDIVIg. Low-dose rituximab was sufficient to deplete B-cells from allografts in AMR. Further studies will explore the effect of treatment on the phenotype and signalling pathways of infiltrating cells and other important cell types in AMR such as platelets, plasma and NK cells.

To cite this abstract in AMA style:

Mulley W, Nikolic-Paterson D, Longano A, Han Y, Ma F, Kanellis J, Ramessur S. The Impact of Therapy On the Inflammatory Infiltrate in Renal Allografts With Acute and Chronic Antibody Mediated Rejection [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/the-impact-of-therapy-on-the-inflammatory-infiltrate-in-renal-allografts-with-acute-and-chronic-antibody-mediated-rejection/. Accessed November 21, 2024.

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