Not All HLA Mismatches Are Equal: Determining the Relative De Novo DSA Induction Capacity of HLA Mismatches

V. Jucaud,¹ L. Rebellato,² K. Briley,² A. Maldonado,³ C. Haisch,² P. Bolin,² S. Kendrick,⁴ H. Jones,⁴ K. McLawhorn,⁴ D. Leeser,² M. Everly.¹

¹Terasaki Research Institute, Los Angeles, CA
²East Carolina University, Greenville, NC
³Vidant Medical Center, Greenville, NC
⁴Eastern Nephrology Associates, Greenville, NC.

Meeting: 2018 American Transplant Congress

Abstract number: 515

Keywords: HLA antibodies, HLA antigens, Immunogenicity, Kidney transplantation

Session Information

Session Name: Concurrent Session: Kidney Donor Selection / Management Issues - 2

Session Type: Concurrent Session

Date: Tuesday, June 5, 2018

Session Time: 4:30pm-6:00pm

Presentation Time: 4:30pm-4:42pm

Location: Room 6E

We studied the immunogenicity, defined as the development of de novo DSA (dnDSA), of HLA-A, -B, -DR and -DQ MM (serological) in a cohort of 197 kidney transplant patients from ECU (Greenville, NC). The cohort is predominantly African-American patients receiving kidneys from mostly Caucasian donors, and who received calcineurin inhibitors as first-line immunosuppression. Patients were screened for dnDSA using Single Antigen Beads 1, 3, 6, 12 months post-transplant, and bi-annually thereafter.

A total of 977 MM were studied, of which 244 led to the formation of dnDSA. DQ MM were significantly more immunogenic than MM from other loci (Figure 1A), accounting for 44% of all dnDSA produced. Among the highly immunogenic MM (≥25% immunogenicity and MM frequency≥8), DQ5 MM were the most immunogenic where 64% MM led to the formation of dnDSA, followed by DQ7 (62%), DQ4 (56%), DQ6 (55%), DQ2 (49%), A30 (45%), DQ8 (44%), A1 (41%), B57 (38%), A11 (35%), DQ9 (33%), B51 (29%), DR7 (29%), and A32 (25%) (Figure 1B). The MM with low immunogenicity (<25% immunogenicity and MM frequency<8) include: A2, A3, A23, A24, A26, A29, A34, A36, A66, A68, B7, B8 B13, B18, B27, B38, B41, B42, B44, B45, B50, B52, B53, B58, B60, B61, and B64 (for HLA class I); and DR1, DR103, DR4, DR8, DR10, DR11, DR12 DR13, DR15, and DR17(for HLA class II). Last, 75% of MM did not lead to the formation of dnDSA despite the high frequency of some (Figure 1C).

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

CITATION INFORMATION: Jucaud V., Rebellato L., Briley K., Maldonado A., Haisch C., Bolin P., Kendrick S., Jones H., McLawhorn K., Leeser D., Everly M. Not All HLA Mismatches Are Equal: Determining the Relative De Novo DSA Induction Capacity of HLA Mismatches Am J Transplant. 2017;17 (suppl 3).

To cite this abstract in AMA style:

Jucaud V, Rebellato L, Briley K, Maldonado A, Haisch C, Bolin P, Kendrick S, Jones H, McLawhorn K, Leeser D, Everly M. Not All HLA Mismatches Are Equal: Determining the Relative De Novo DSA Induction Capacity of HLA Mismatches [abstract]. https://atcmeetingabstracts.com/abstract/not-all-hla-mismatches-are-equal-determining-the-relative-de-novo-dsa-induction-capacity-of-hla-mismatches/. Accessed November 23, 2024.

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