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. 2023 Mar 17;12(6):2335.
doi: 10.3390/jcm12062335.

Complement Binding Anti-HLA Antibodies and the Survival of Kidney Transplantation

Claudia M Muñoz-Herrera  1   2   3   4 , Juan Francisco Gutiérrez-Bautista  1   3   5 , Miguel Ángel López-Nevot  1   3   5
Affiliations

Complement Binding Anti-HLA Antibodies and the Survival of Kidney Transplantation

Claudia M Muñoz-Herrera et al. J Clin Med. .

Abstract

Background: Antibody-mediated rejection (AMR) is one of the most important challenges in the context of renal transplantation, because the binding of de novo donor-specific antibodies (dnDSA) to the kidney graft triggers the activation of the complement, which in turn leads to loss of transplant. In this context, the objective of this study was to evaluate the association between complement-fixing dnDSA antibodies and graft loss as well as the possible association between non-complement-fixing antibodies and transplanted organ survival in kidney transplant recipients.

Methods: Our study included a cohort of 245 transplant patients over a 5-year period at Virgen de las Nieves University Hospital (HUVN) in Granada, Spain.

Results: dnDSA was observed in 26 patients. Of these patients, 17 had non-complement-fixing dnDSA and 9 had complement-fixing dnDSA.

Conclusions: Our study demonstrated a significant association between the frequency of rejection and renal graft loss and the presence of C1q-binding dnDSA. Our results show the importance of the individualization of dnDSA, classifying them according to their ability to activate the complement, and suggest that the detection of complement-binding capacity by dnDSA could be used as a prognostic marker to predict AMR outcome and graft survival in kidney transplant patients who develop dnDSA.

Keywords: AMR, antibody-mediated rejection; DSA, donor-specific antibodies; complement-fixing DSA; dnDSA, de novo donor-specific antibodies; kidney graft; renal transplant.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Association between the presence of complement-binding dnDSA and rejection events. A higher number of rejection events was observed in patients who developed C1q-binding dnDSA, with respect to those who did not bind complement (p = 0.009).
Figure 2
Figure 2
Kaplan–Meier curves to determine renal graft survival, according to the presence or absence of dnDSA. Lower renal graft survival is observed in patients who develop dnDSA.
Figure 3
Figure 3
Kaplan–Meier curves to determine renal graft survival according to C1q-binding capacity by dnDSAs. Lower renal graft survival is observed in patients who develop complement-binding dnDSAs, whereas survival is similar for the other two populations.
Figure 4
Figure 4
Association between the presence of complement-binding dnDSA and renal graft loss. Renal graft loss was observed in patients who developed C1q-binding DSA, with respect to those who did not (p = 0.002).
Figure 5
Figure 5
Association between MFI values and C1q binding capacity. Non-binding dnDSA comprise MFI values below 5000, whereas C1q-binding dnDSA are more related to MFI values above 10,000 (p = 0.017).
See this image and copyright information in PMC

References

    1. Hernández D., Alonso-Titos J., Armas-Padrón A.M., Ruiz-Esteban P., Cabello M., López V., Fuentes L., Jironda C., Ros S., Jiménez T., et al. Mortality in Elderly Waiting-List Patients Versus Age-Matched Kidney Transplant Recipients: Where Is the Risk? Kidney Blood Press. Res. 2018;43:256–275. doi: 10.1159/000487684. - DOI - PubMed
    1. Kaballo M.A., Canney M., O’Kelly P., Williams Y., O’Seaghdha C.M., Conlon P.J. A Comparative Analysis of Survival of Patients on Dialysis and after Kidney Transplantation. Clin. Kidney J. 2018;11:389–393. doi: 10.1093/ckj/sfx117. - DOI - PMC - PubMed
    1. Kovesdy C.P. Clinical Trials in End-Stage Renal Disease—Priorities and Challenges. Nephrol. Dial. Transplant. 2019;34:1084–1089. doi: 10.1093/ndt/gfz088. - DOI - PubMed
    1. Robinson J., Halliwell J., Hayhurst J., Flicek P., Parham P., Marsh S. The IPD and IMGT/HLA Database: Allele Variant Databases. [(accessed on 20 May 2019)]. Available online: http://hla.alleles.org/alleles/index.html. - PubMed
    1. Edward J. A Historical Perspective on Evidence—Based Immunology. Elsevier; Amsterdam, The Netherlands: 2016. Moticka Transplantation Immunology; pp. 317–327.