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2020, Number 3

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Rev Mex Traspl 2020; 9 (3)

History of a previous renal transplant as the most important event for C3d positive HLA antibodies and IgG subclass identification

Casillas-Abundis A, Alberú J, Morales-Buenrostro LE, Llorente L, Lima G, Arvizu A, De Santiago A, Vilatobá M, Granados J, Cruz R, Contreras AG, Arreola-Guerra JM

Language: English
References: 33
Page: 109-119
PDF size: 398.26 Kb.


ABSTRACT

Introduction: Antibodies against HLA antigens are the main immunologic barrier for kidney transplantation. These antibodies either preformed, or developed de novo after transplant, precede antibody-mediated rejection, which is the most important cause of graft failure. The capability to further analyze these antibodies is allowing the creation of immunologic risk profiles that are associated with higher rejection rates and graft loss. Some of the most studied risk characteristics of the antibodies are the Mean Fluorescence Intensity (MFI), HLA antigenic specificity, IgG subclasses and the antibodies’ ability to fix complement. The objective of this study is to describe the characteristics of pre-transplant HLA antibodies and the sensitizing events related to them (previous kidney transplant, pregnancies and transfusions). Material and methods: This is an observational, transversal and descriptive study. Sera samples from previously sensitized potential kidney transplant recipients were evaluated; anti-HLA antibodies were determined using single antigen beads (SAB) (Luminex), as well as IgG subclasses of these antibodies and its ability for complement activation using the C3d assay. Results: A total of 89 patients’ sera samples were analyzed, with a mean age 33.3 years (± 13.8) and 60.2% males (n = 54). History of previous kidney transplant was found in 20.4% (n = 18) of the patients, history of at least one previous pregnancy 17.2% (n = 15) of the female patients and previous transfusions in 60.2% (n = 54). A total of 1,771 anti-HLA antibodies were detected, 367 (20.1%) with at least one IgG subclass and 216 (12.1%) complement activation capacity (C3d+). The factors found to be related with a higher detection rate of IgG subclasses were: SAB MFI › 4,000 (OR 15.9, 95% CI 11.2-22.4, p = ‹ 0.01), positive C3d assay (OR 3.4, 95% CI 2.4-4.9, p = ‹ 0.01) and HLA-B specific antibodies (OR 2.3, 95% CI 1.7-3.2, p = ‹ 0.01). The factors found to be associated with a positive C3d assay were: SAB MFI › 4,000 (OR 1.15, 95% CI 1.10-1.21, p = ‹ 0.01), HLA-DQ specific antibodies (OR 4.37, 95% CI 2.21-8.66, p ‹ 0.01), HLA-DR specific antibodies (OR 10.24, 95% CI 5.07-20.65, p ‹ 0.01), HLA-B specific antibodies (OR 0.35, 95% CI 0.18-0.67, p = ‹ 0.01) and the detection of at least one IgG subclass (OR 15.8, 95% CI 7.79-32.2, p = ‹ 0.01). Patients with a history of a previous kidney transplant were found to have more anti-HLA antibodies, higher MFI titles, IgG subclasses were detected in all of these patients and they had more positive C3d antibodies. The most prevalent IgG subclass detected in this population was IgG1 (n = 351, 95.6%). Conclusions: In general, the IgG subclasses and the C3d assay were not able to detect or characterize the anti-HLA antibodies in most of the cases. Remarkably, in all the patients with history of previous kidney transplant IgG subclasses were identified and 90% of them yielded a positive C3d assay for complement activation. The ability of the assay to detect IgG subclasses and C3d positive antibodies was related with the MFI of the anti-HLA antibodies, which were significantly higher in patients with previous kidney transplant.


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