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Searching for Recipient-HLA Class II and Donor-HLA-Derived Peptide Complexes Inducing Protective Effect against De Novo Donor-Specific HLA Antibodies Formation in Kidney Transplantation

T. Tomosugi,1 K. Iwasaki,1 M. Okumura,1 Y. Matsuoka,1 K. Horimi,1 M. Okada,2 Y. Watarai,2 T. Kobayashi.1

1Kidney Transplant Surgery, Aichi Medical University, Nagakute, Aichi, Japan
2Transplant and Endocrine Surgery, Nagoya Daini Red Cross Hospital, Nagoya, Aichi, Japan.

Meeting: 2018 American Transplant Congress

Abstract number: C36

Keywords: Allorecognition, HLA antibodies, Kidney transplantation, MHC class II

Session Information

Session Name: Poster Session C: Kidney Chronic Antibody Mediated Rejection

Session Type: Poster Session

Date: Monday, June 4, 2018

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall 4EF

De novo donor-specific HLA antibodies (dnDSA) are recognized as a risk factor for late deterioration of renal allograft function. dnDSA production occurs via the indirect allorecognition pathway in which donor HLA is processed by the recipient's antigen-presenting cells and presented via recipient HLA class II to CD4+ T cells. Recently, complex comprising particular HLA class II and peptide has been reported to play a protective roll against producing the peptide-specific antibodies through the induction of peptide-specific regulatory T cells in the model of Goodpasture disease.

Here we hypothesize that complex comprising particular recipient-HLA class II and donor-HLA-derived peptide may also have a protective effect against dnDSA formation in kidney transplantation, and attempted to show some supportive data.

A total of 923 adult living donor kidney transplants without preformed DSA between 1983 and 2017 were analyzed. HLA types (at least HLA-A, B, DRB1) for donor-recipient pairs were determined, and pre- and posttransplant surveillance for dnDSA had been achieved by Luminex-based assays.

In the present study, dnDSA had been detected in 147 recipients. Some complexes tended to be seen more in dnDSA negative group. For example, while recipient DRB1*04:05 and donor DRB1*09:01 complex was seen in 42 cases among dnDSA negative group (n=776), this complex was only seen in 2 cases among dnDSA positive group (n=147) (5.4% vs 1.4%, p<0.05).

With the purpose of validating the protective effect of these complexes, we performed mixed lymphocyte reaction assays (MLR). In cases which contained statistically protective complex, proliferation of recipient CD4+ T cell co-cultured with donor PBMC tended to be suppressed compared with cases which didn't contain protective complex, though there was no statistically significant difference (Stimulation Index 1.73±1.17 vs 7.92±7.54, p=0.07).

These results suggest the possibility that a certain HLA class II and peptide complex may play a protective role in alloreactive immune response against dnDSA formation in kidney transplantation.

CITATION INFORMATION: Tomosugi T., Iwasaki K., Okumura M., Matsuoka Y., Horimi K., Okada M., Watarai Y., Kobayashi T. Searching for Recipient-HLA Class II and Donor-HLA-Derived Peptide Complexes Inducing Protective Effect against De Novo Donor-Specific HLA Antibodies Formation in Kidney Transplantation Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Tomosugi T, Iwasaki K, Okumura M, Matsuoka Y, Horimi K, Okada M, Watarai Y, Kobayashi T. Searching for Recipient-HLA Class II and Donor-HLA-Derived Peptide Complexes Inducing Protective Effect against De Novo Donor-Specific HLA Antibodies Formation in Kidney Transplantation [abstract]. https://atcmeetingabstracts.com/abstract/searching-for-recipient-hla-class-ii-and-donor-hla-derived-peptide-complexes-inducing-protective-effect-against-de-novo-donor-specific-hla-antibodies-formation-in-kidney-transplantation/. Accessed June 4, 2025.

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