Peripheral Blood Immune Response-Related Gene Analysis for Evaluating the Development of Subclinical Antibody-Mediated Rejection

T. Yamamoto,¹ K. Iwasaki,² K. Murotani,³ A. Takeda,⁴ M. Tsujita,⁴ T. Hiramitsu,⁴ N. Goto,⁴ S. Narumi,⁴ Y. Watarai,⁴ K. Uchida,² T. Kobayashi.⁵

¹Xenotransplantation, University of Alabama at Birmingham, Birmingham, AL
²Kidney Disease and Transplant Immunology, Aichi Medical University, Nagakute, Japan
³Biostatistics, Aichi Medical University, Nagakute, Japan
⁴Kidney Center, Nagoya Daini Red Cross Hospital, Nagoya, Japan
⁵Renal Transplant Surgery, Aichi Medical University, Nagakute, Japan.

Meeting: 2018 American Transplant Congress

Abstract number: A24

Keywords: Gene expression, HLA antibodies, Kidney transplantation

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: Noninvasive methods for the early diagnosis of chronic antibody-mediated rejection (cAMR) are desired for patients with de novo (dn) donor-specific HLA antibody (DSA) because of the lack of effective methods other than graft biopsy. The aim of this study to elucidate the clinical relevance of immune-related gene expression in peripheral blood of kidney transplant recipients. Materials and Methods: Fourteen key molecules (Foxp3, CTLA-4, CCR7, TGF-β, IGLL-1, IL-10, ITCH, CBLB, Bcl-6, CXCR5, granzyme B, CIITA, Baff, TOAG-1/TCAIM) related to regulatory/cytotoxic function of immune cells were examined in the peripheral blood of 93 kidney transplant recipients by RT-PCR. The expression levels were compared among patients who had clinical cAMR with dn DSA (group A, N=16), subclinical cAMR with dn DSA (group B, N=17), negative cAMR with dn DSA (group C, N=21), and clinically stable function without dn DSA (group D, N=39). Results: On multivariate analysis, CIITA mRNA expression levels in groups B and C (potential risk groups for clinical cAMR) were significantly lower than those in group D (p < 0.01). Moreover, the CTLA-4 mRNA expression in group A (clinical cAMR group due to dn DSA) was significantly higher than that in groups B and C (p < 0.01). However, no biomarker could effectively differentiate between groups B and C. ROC curve analysis suggested that CIITA [area under the curve (AUC) = 0.902] and CTLA-4 (AUC = 0.785) may serve as valuable biomarkers of the stage of dn DSA production and clinical cAMR, respectively. Conclusions: In addition to dn DSA screening, monitoring of CIITA and CTLA-4 in peripheral blood could offer useful information on the time course of the development of cAMR.

CITATION INFORMATION: Yamamoto T., Iwasaki K., Murotani K., Takeda A., Tsujita M., Hiramitsu T., Goto N., Narumi S., Watarai Y., Uchida K., Kobayashi T. Peripheral Blood Immune Response-Related Gene Analysis for Evaluating the Development of Subclinical Antibody-Mediated Rejection Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Yamamoto T, Iwasaki K, Murotani K, Takeda A, Tsujita M, Hiramitsu T, Goto N, Narumi S, Watarai Y, Uchida K, Kobayashi T. Peripheral Blood Immune Response-Related Gene Analysis for Evaluating the Development of Subclinical Antibody-Mediated Rejection [abstract]. https://atcmeetingabstracts.com/abstract/peripheral-blood-immune-response-related-gene-analysis-for-evaluating-the-development-of-subclinical-antibody-mediated-rejection/. Accessed May 8, 2025.

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