Which is More Important for Predicting De Novo DSA Production, B Cell Epitope (EPLET) or T Cell Epitope (PIRCHE) Analysis ?
1Aichi Medical University School of Medicine, Nagakute, Japan, 2Nagoya Daini Red Cross Hospital, Nagoya, Japan, 3PIRCHE AG, Berlin, Germany, 4UMC Utrecht, Utrecht, Netherlands
Meeting: 2022 American Transplant Congress
Abstract number: 120
Keywords: Epitopes, Histocompatibility, HLA antibodies, Kidney transplantation
Topic: Clinical Science » Kidney » 45 - Kidney Chronic Antibody Mediated Rejection
Session Information
Session Name: Kidney Complications: Chronic Antibody Mediated Rejection & Immune Mediated Late Graft Failure
Session Type: Rapid Fire Oral Abstract
Date: Sunday, June 5, 2022
Session Time: 5:30pm-7:00pm
Presentation Time: 6:40pm-6:50pm
Location: Hynes Room 302
*Purpose: De novo donor-specific antibodies (dnDSA) can cause chronic ABMR, resulting in poor prognosis. Recently, mismatch at B cell epitope level, i.e. EPLET mismatch, has been reported to be associated with dnDSA production. Similar results have also been demonstrated for T cell epitope matching, i.e. PIRCHE score. In the study of kidney transplant recipients with non-donor specific HLA antibodies, shared T cell epitope-positive patients showed early dnDSA production and death censored graft failure. Such donor reactive memory T cells could be estimated by PIRCHE. We investigated whether the significance of EPLET and PIRCHE analysis differs depending on the presence or absence of donor-specific sensitization history.
*Methods: Subgroup analysis of the previous study was performed. 691 living donor kidney transplants without preformed DSA between 2008 and 2015 were divided into two groups, (A) recipients with prior pregnancy, receiving a kidney from husband or child and (B) recipients with no prior donor-specific immunization. Only Class II dnDSA (DR and DQ) were considered. EPLET mismatches and PIRCHE scores were determined by HLAMatchmaker ver 3.1 (antibody-verified, DRB and DQB) and PIRCHE web service, respectively.
*Results: Twelve and 88 developed dnDSA in (A) potentially sensitized patients (n=112) and (B) unsensitized patients (n=579), respectively. EPLET mismatches of dnDSA (+) and dnDSA (-) were 9.3±4.3 vs 7.4±3.7 (p=0.2358) and 7.9±3.3 vs 5.2±4.1 (p<0.001) in (A) and (B) group, respectively. PIRCHE scores of dnDSA (+) and dnDSA (-) were 391±179 vs 268±138 (p=0.0135), 248±124 vs 193±135 (p<0.001) in (A) and (B), respectively. Univariate analysis revealed a significant difference in EPLET mismatch, PIRCHE score and acute T cell mediated rejection between dnDSA(+) and dnDSA(-). Multivariate analysis showed dnDSA was significantly associated with PIRCHE score in (A), whereas EPLET mismatch was more significant in (B) (Table 1).
*Conclusions: EPLET mismatch and PIRCHE score were effective in predicting dnDSA production particularly in patients without and with sensitization history of donor HLA, respectively. This suggests that B cell epitopes are related to primary response, whereas T cell epitopes are associated with memory response more closely, after kidney transplantation.
| (A) Potentially sensitized (n=112) | (B) Unsensitized (n=579) | |
| EPLET mismatch (DRB+DQB) | 1.094(0.910-1.325) p=0.3389 | 1.096(1.035-1.157) p=0.0020 |
| In(PIRCHE score+1) | 4.098(1.055-19.029) p=0.0409 | 1.442(1.048-2.086) p=0.0224 |
| Acute T cell mediated rejection | 7.189(1.513-27.364) p=0.0167 | 2.197(1.241-3.675) p=0.0082 |
To cite this abstract in AMA style:
Kobayashi T, Tomosugi T, Sakamoto S, Ashimine S, Iwasaki K, Niemann M, Spierings E, Miwa Y, Okumura M, Ishiyama K, Takeda A, Goto N, Narumi S, Watarai Y. Which is More Important for Predicting De Novo DSA Production, B Cell Epitope (EPLET) or T Cell Epitope (PIRCHE) Analysis ? [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/which-is-more-important-for-predicting-de-novo-dsa-production-b-cell-epitope-eplet-or-t-cell-epitope-pirche-analysis/. Accessed November 21, 2024.« Back to 2022 American Transplant Congress