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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