We studied the relative immunogenicity of HLA-A, -B, -C, -DR and -DQ MM (serological) in a cohort of 291 kidney transplant patients from the BENEFIT and BENEFIT-EXT trials who received a calcineurin inhibitor (cyclosporine) as first-line immunosuppression.

A total of 1129 MM were studied. From these MM, 60 de novo DSA (dnDSA) appeared. DQ MM were significantly more immunogenic than MM from other loci (Figure 1A), accounting for 35% of all dnDSA produced. Among the highly immunogenic MM (≥10% immunogenicity and MM frequency≥7), DQ5 and DQ7 were the most immunogenic, in that 45% of MM led to the formation of dnDSA, followed by DQ2 (29%), DQ8 (22%), DQ6 (14%), DQ4 (14%), A29 (11%), A28 (11%), A1 (11%), A24 (10%), DR3 (10%), and A11 (10%) (Figure 1B). The less immunogenic MM (<10% immunogenicity and MM frequency<7) included: A2, A23, A26, A32, B8, B27, B45, B50, B51, B57, Cw5, Cw6, and Cw7 (for HLA class I); and DR3, DR4, DR13, DR14, DR16, DR17, and DQ3 (for HLA class II). Lastly, 95% of MM did not lead to the formation of dnDSA (Figure 1C).

With the use of a calcineurin inhibitor as first-line immunosuppression, MM at DQ loci are the most immunogenic compared to MM from other HLA loci. To prevent development of dnDSA and antibody mediated graft injury, highly immunogenic MM (upper-left quadrant in Figure 1B) should be considered in donor/recipient matching. Many MM did not induce dnDSA (listed below the plot in Figure 1), and may not be immunogenic.

CITATION INFORMATION: Jucaud V., Roberts M., Gebel H., Bray R., Everly M. Determining the Relative Immunogenicity of HLA Mismatches with Calcineurin Inhibitor Immunosuppression: An Analysis of the BENEFIT and BENEFIT-EXT Renal Transplant Cohort Am J Transplant. 2017;17 (suppl 3).

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