Ann Lab Med.  2023 Jul;43(4):364-374. 10.3343/alm.2023.43.4.364.

Impact of Low-Level Donor-Specific Anti-HLA Antibody on Posttransplant Clinical Outcomes in Kidney Transplant Recipients

• Lee H
• Lee H
• Eum SH
• Ko EJ
• Min JW
• Oh EJ
• Yang CW
• Chung BH

• KMID: 2551954
• DOI: http://doi.org/10.3343/alm.2023.43.4.364

Abstract

Background
The clinical significance of low-level donor-specific anti-HLA antibody (low-DSA) remains controversial. We investigated the impact of low-DSA on posttransplant clinical outcomes in kidney transplant (KT) recipients.
Methods
We retrospectively reviewed 1,027 KT recipients, namely, 629 living donor KT (LDKT) recipients and 398 deceased donor KT (DDKT) recipients, in Seoul St. Mary’s Hospital (Seoul, Korea) between 2010 and 2018. Low-DSA was defined as a positive anti-HLA-DSA result in the Luminex single antigen assay (LABScreen single antigen HLA class I - combi and class II - group 1 kits; One Lambda, Canoga Park, CA, USA) but a negative result in a crossmatch test. We compared the incidence of biopsy-proven allograft rejection (BPAR), changes in allograft function, allograft survival, patient survival, and posttransplant infections between subgroups according to pretransplant low-DSA.
Results
The incidence of overall BPAR and T cell-mediated rejection did not differ between the subgroups. However, antibody-mediated rejection (ABMR) developed more frequently in patients with low-DSA than in those without low-DSA in the total cohort and the LDKT and DDKT subgroups. In multivariate analysis, low-DSA was identified as a risk factor for ABMR development. Its impact was more pronounced in DDKT (odds ratio [OR]: 9.60, 95% confidence interval [CI]: 1.79–51.56) than in LDKT (OR: 3.76, 95% CI: 0.99–14.26) recipients. There were no significant differences in other outcomes according to pretransplant low-DSA.
Conclusions
Pretransplant low-DSA has a significant impact on the development of ABMR, and more so in DDKT recipients than in LDKT recipients, but not on long-term outcomes.

Keyword

Donor-specific anti-HLA antibody; Donor-specific antibody; Kidney transplantation; Rejection; Graft survival; Infection

Figure

• 

  Fig. 1 Distribution of the patient population according to donor type and presence of pretransplant low-DSA. Abbreviations: BMT, bone marrow transplantation; DDKT, deceased donor kidney transplant; LDKT, living donor kidney transplant; low-DSA, low-level donor-specific anti-HLA antibody; no-DSA, negative donor-specific anti-HLA antibody; SOT, solid organ transplantation; XM, crossmatch.

• 

  Fig. 2 Correlation between XM positivity and HLA-DSA MFI. (A) represents CDC-XM positivity and (B) represents FCXM positivity. Abbreviations: CDC-XM, complement-dependent cytotoxicity crossmatch; FCXM, flow cytometry crossmatch; HLA-DSA, donor-specific anti-HLA antibody; MFI, mean fluorescence intensity; XM, crossmatch.

• 

  Fig. 3 Immunological characteristics of HLA-DSA according to the strength, class, and specificities of HLA-DSA. Numbers above bar graphs are median HLA-DSA MFI values. Pie graphs represent the percentage of HLA-DSA specificity within each HLA-DSA group classified by the peak MFI value. Abbreviations: DDKT, deceased donor kidney transplant; HLA-DSA, donor-specific anti-HLA antibody; LDKT, living donor kidney transplant.

• 

  Fig. 4 Development of BPAR in the first year of transplantation according to the presence of low-DSA. The incidences of overall BPAR, TCMR, and ABMR are compared in the total cohort and the LDKT and DDKT subgroups. Abbreviations: ABMR, antibody-mediated rejection; BPAR, biopsy-proven allograft rejection; DDKT, deceased donor kidney transplant; LDKT, living donor kidney transplant; no-DSA, negative donor-specific anti-HLA antibody; low-DSA, low-level donor-specific anti-HLA antibody; TCMR, T cell-mediated rejection. *P<0.05.

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