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Role of CMV, BKV, and Immunosupression Non-Adherence in Early and Late De Novo Donor Specific Anti-HLA Antibody Development and Outcomes

M. Everly,1 L. Rebellato,2 K. Briley,2 A. Maldonado,3 P. Bolin,2 C. Haisch,2 W. Kendrick,4 S. Kendrick,4 C. Morgan,2 R. Harland,2 P. Terasaki.1

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

Meeting: 2015 American Transplant Congress

Abstract number: A87

Keywords: Alloantibodies, Cytomeglovirus, Polyma virus, Survival

Session Information

Session Name: Poster Session A: Kidney Antibody Mediated Rejection

Session Type: Poster Session

Date: Saturday, May 2, 2015

Session Time: 5:30pm-7:30pm

 Presentation Time: 5:30pm-7:30pm

Location: Exhibit Hall E

This analysis aims to identify appropriate de novo DSA (dnDSA) screening points and delineate the post-transplant (txp) scenarios preceding dnDSA development to aid in clinical understanding and therapeutic decision making.

Methods: All pre-txp DSA negative, HLA-mismatched primary renal txp patients transplanted between 3/99 and 12/10 (n=341) were included if they developed dnDSA post-txp (n=107). Serum was collected pre-txp and post-txp at 1, 3, 6, 9, 12 months and bi-annually, thereafter. The sera were retrospectively tested for HLA IgG antibodies via LABScreen single antigen bead assay.

Results: 107 patients (31%) were found to develop dnDSA over the 3 -14 years of post-txp follow-up. dnDSA development was highest early post-txp (first 24 months post-txp) compared to late post-transplant (>24 months post-txp) (Figs A&B). Specifically, dnDSA was highest in the first 6 months post-txp and rates declining thereafter. When investigating post-txp events that preceded dnDSA, we determined that 37% of dnDSA had a pre-dnDSA history for infection (especially polyoma or cytomegalovirus (BKV or CMV) infection). dnDSA preceeded by BKV or CMV was 3-fold higher in the first 24 months post-txp. Non-adherence (documented and suspected) was found in 17% of dnDSA cases overall with rates 2-fold higher later (>24 months) post-txp (Figs C&D). Overall, 39% of total dnDSA cases had no significant events prior to dnDSA. Actual 3-year post-dnDSA survival (n=99) in those with pre-dnDSA BKV, CMV, or non-adherence was significantly poorer (Fig, p=0.04).

Conclusion: Overall these findings indicate that (1) most dnDSA occur in the first 6-months post-txp, (2) Early dnDSA is related to infection especially BKV and CMV, (3) late dnDSA is more commonly related to non-adherence and (4) dnDSA following non-adherence or BKV/CMV results in significantly poorer outcomes.

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To cite this abstract in AMA style:

Everly M, Rebellato L, Briley K, Maldonado A, Bolin P, Haisch C, Kendrick W, Kendrick S, Morgan C, Harland R, Terasaki P. Role of CMV, BKV, and Immunosupression Non-Adherence in Early and Late De Novo Donor Specific Anti-HLA Antibody Development and Outcomes [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/role-of-cmv-bkv-and-immunosupression-non-adherence-in-early-and-late-de-novo-donor-specific-anti-hla-antibody-development-and-outcomes/. Accessed May 8, 2025.

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