Layla Kamal1, Pilib Ó Broin, Yi Bao, Maria Ajaimy, Michelle Lubetzky, Anjali Gupta, Graciela de Boccardo, James Pullman, Aaron Golden, Enver Akalin. 1. 1 Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, New York, NY. 2 Department of Genetics, Division of Computational Genetics, Montefiore-Einstein Center for Transplantation, Montefiore Medical Center, The University Hospital for Albert Einstein College of Medicine, Bronx, NY. 3 Department of Pathology, Albert Einstein College of Medicine, Bronx, NY. 4 Department of Mathematical Sciences, Yeshiva University, New York, NY.
Abstract
BACKGROUND: We aimed to investigate the clinical, histopathological, and molecular factors associated with allograft loss in transplant glomerulopathy (TGP) patients. METHODS: Of the 525 patients who underwent clinically indicated kidney biopsies, 52 (10%) had diagnosis of TGP. Gene expression profiles of 28 TGP and 11 normal transplant kidney biopsy samples were analyzed by Affymetrix HuGene 1.0 ST expression arrays. RESULTS: Over a median follow up of 23 months (1-46 months) after the diagnosis of TGP by biopsy, 17 patients (32%) lost their allografts at a median of 16 months (1-44 months). There was no difference between the 2 groups in terms of any demographic variables, serum creatinine, panel reactive antibody levels, donor-specific antibody frequency, or mean fluorescence intensity values. Patients who lost their allograft had a significantly higher median spot protein to creatinine ratio 2.81 (1.20-6.00) compared to no graft loss patients 1.16 (0.15-2.53), (P < 0.01), and a trends toward a higher mean chronic glomerulopathy (cg) score (1.65 ± 0.93 vs 1.11 ± 0.93) (P = 0.05). There was also no difference in microvascular inflammation or any other Banff injury scores between the 2 groups. Although 117 gene transcripts were upregulated in both groups, 86 and 57 were upregulated in graft loss and functioning allograft groups, respectively. There were significantly increased levels of intragraft endothelial cell-associated transcripts, gene transcripts associated with complement cascade, interleukins and their receptors and granulysin in graft loss patients compared to patients with a functioning allograft. CONCLUSION: Our results demonstrate differential intragraft gene expression profiles in TGP patients with allograft loss.
BACKGROUND: We aimed to investigate the clinical, histopathological, and molecular factors associated with allograft loss in transplant glomerulopathy (TGP) patients. METHODS: Of the 525 patients who underwent clinically indicated kidney biopsies, 52 (10%) had diagnosis of TGP. Gene expression profiles of 28 TGP and 11 normal transplant kidney biopsy samples were analyzed by Affymetrix HuGene 1.0 ST expression arrays. RESULTS: Over a median follow up of 23 months (1-46 months) after the diagnosis of TGP by biopsy, 17 patients (32%) lost their allografts at a median of 16 months (1-44 months). There was no difference between the 2 groups in terms of any demographic variables, serum creatinine, panel reactive antibody levels, donor-specific antibody frequency, or mean fluorescence intensity values. Patients who lost their allograft had a significantly higher median spot protein to creatinine ratio 2.81 (1.20-6.00) compared to no graft loss patients 1.16 (0.15-2.53), (P < 0.01), and a trends toward a higher mean chronic glomerulopathy (cg) score (1.65 ± 0.93 vs 1.11 ± 0.93) (P = 0.05). There was also no difference in microvascular inflammation or any other Banff injury scores between the 2 groups. Although 117 gene transcripts were upregulated in both groups, 86 and 57 were upregulated in graft loss and functioning allograft groups, respectively. There were significantly increased levels of intragraft endothelial cell-associated transcripts, gene transcripts associated with complement cascade, interleukins and their receptors and granulysin in graft loss patients compared to patients with a functioning allograft. CONCLUSION: Our results demonstrate differential intragraft gene expression profiles in TGPpatients with allograft loss.
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Authors: Qiang Zhang; Klemens Budde; Danilo Schmidt; Fabian Halleck; Michael Duerr; Marcel G Naik; Manuel Mayrdorfer; Wiebke Duettmann; Frederick Klauschen; Birgit Rudolph; Kaiyin Wu Journal: Front Med (Lausanne) Date: 2021-07-02