Clinical Significance and Therapeutic Potential of Orosomucoid 1 for Chronic Active Antibody Mediated Rejection in Kidney Transplant Recipients

H. Higuchi,^1,2 K. Hotta,¹ D. Iwami,¹ J-.J. Jiang,² D. Kamimura,² Y. Arima,² T. Atsumi,² Y. Takada,^1,2 H. Harada,³ M. Murakami,² N. Shinohara.¹

¹Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
²Division of Molecular Psychoimmunology, Institute for Genetic Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan
³Department of Kidney Transplant Surgery, Sapporo City General Hospital, Sapporo, Hokkaido, Japan.

Meeting: 2018 American Transplant Congress

Abstract number: A22

Keywords: Inflammation, Kidney transplantation, Nuclear factor-kappa B (NF-kB), Rejection

Session Information

Session Name: Poster Session A: Biomarkers, Immune Monitoring and Outcomes

Session Type: Poster Session

Date: Saturday, June 2, 2018

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

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

Location: Hall 4EF

［Background］We reported a molecular mechanism to develop chronic inflammation (CI), called the inflammation amplifier (IA). IA is activated by concomitant activation of NFkB and STAT3 in non-immune cells and enhances NFkB activation, proliferates inflammatory mediators such as IL-6 and chemokines. We suggested that Orosomucoid1 (ORM1) is a candidate gene regulating IA by a shRNA-mediated genome wide-screening. Therefore, we investigated the contribution of ORM1 during chronic active antibody mediated rejection (CAAMR) process in kidney allograft (KA) and the potential for new diagnostic biomarker and therapeutic targets.［Methods/Results］We measured serum and urinary ORM1 in kidney transplant recipients (KTR), compared clinical data among patient groups with normal histology, interstitial fibrosis and tubular atrophy, or CAAMR. Urinary ORM1 in CAAMR were significantly high compared to KTR with no rejection, while serum ORM1 and urinary NAG levels showed no difference. Immunohistochemistry of allograft biopsy samples showed strong expression of ORM1, phosphorylated NFkB and STAT3 in tubular cells in CAAMR samples. To address the underline molecular mechanism, we used renal proximal tubule epithelial cells (RPTEC) for in vitro assay. ORM1 was induced in RPTEC after IA activation. Furthermore, inhibition of ORM1 by siRNA suppressed IA activation. In contrast, addition of ORM1 increased the expression of NFkB-target genes, also exacerbated NFkB-mediated inflammation development in vivo.【Conclusion】CI induced by IA activation play an important role in developing CAAMR. We suggest that ORM1 is a non-invasive biomarker and a possible therapeutic target for CAAMR.

CITATION INFORMATION: Higuchi H., Hotta K., Iwami D., Jiang J-.J., Kamimura D., Arima Y., Atsumi T., Takada Y., Harada H., Murakami M., Shinohara N. Clinical Significance and Therapeutic Potential of Orosomucoid 1 for Chronic Active Antibody Mediated Rejection in Kidney Transplant Recipients Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Higuchi H, Hotta K, Iwami D, Jiang J-J, Kamimura D, Arima Y, Atsumi T, Takada Y, Harada H, Murakami M, Shinohara N. Clinical Significance and Therapeutic Potential of Orosomucoid 1 for Chronic Active Antibody Mediated Rejection in Kidney Transplant Recipients [abstract]. https://atcmeetingabstracts.com/abstract/clinical-significance-and-therapeutic-potential-of-orosomucoid-1-for-chronic-active-antibody-mediated-rejection-in-kidney-transplant-recipients/. Accessed November 25, 2024.

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