ABSTRACT
We report the case of a sensitized woman who underwent successful transplantation after a desensitization protocol, with an optically normal 8-day biopsy. At 3 months, she developed active antibody-mediated rejection (AMR) due to preformed donor-specific antibodies. It was decided to treat the patient with daratumumab, an anti-CD38 monoclonal antibody. The mean fluorescence intensity of donor-specific antibodies decreased, pathologic signs of AMR regressed, and kidney function returned to normal. A molecular assessment of biopsies was retrospectively performed. By doing so, regression of the molecular signature of AMR was evidenced between the second and third biopsies. Interestingly, the first biopsy revealed a gene expression profile of AMR, which helped retrospectively classify this biopsy as AMR, illustrating the relevance of molecular phenotyping of biopsy in high-risk situations such as desensitization.
Subject(s)
Kidney Transplantation , Female , Humans , Retrospective Studies , Kidney Transplantation/adverse effects , Isoantibodies/adverse effects , Antibodies, Monoclonal/therapeutic use , Graft Rejection/drug therapy , Graft Rejection/etiology , Graft Rejection/prevention & control , BiopsyABSTRACT
HLA-DQA1*01:80 differs from HLA-DQA1*01:04:01 by one nucleotide substitution in codon -18 in exon 1.
Subject(s)
Alleles , HLA-DQ alpha-Chains , High-Throughput Nucleotide Sequencing , HLA-DQ alpha-Chains/genetics , Humans , Sequence Analysis, DNAABSTRACT
HLA-C*04:438 differs from HLA-C*04:01:01 by one nucleotide substitution in codon 237 in exon 4.
Subject(s)
Alleles , HLA-C Antigens , High-Throughput Nucleotide Sequencing , Exons/genetics , Genes, MHC Class I , HLA-C Antigens/genetics , HumansABSTRACT
De novo donor-specific antibodies (dnDSA) are associated with antibody-mediated rejection (ABMR) and allograft loss. We tested Immucor* (IM) Luminex Single-antigen beads (LSAB) assay and C3d-fixing antibodies in the setting of dnDSA and subclinical (s) ABMR. This retrospective multicentric study included 123 patients biopsied because of the presence of subclinical de novo DSA detected by One Lamda* Labscreen (MFI > 1000). In 112 patients, sera of the day of the biopsy were available and tested in a central lab with IM Lifecodes LSAB and C3d fixing antibodies assays. In 16 patients (14.3%), no DSA was detected using Immucor test. In 96 patients, at least one DSA was determined with IM. Systematic biopsies showed active sABMR in 30 patients (31.2%), chronic active sABMR in 17 patients (17.7%) and no lesions of sABMR in 49 KT recipients (51%). Intensitity criteria (BCM, BCR and AD-BCR) of DSA were not statistically different between these 3 histological groups. The proportion of patients with C3d-fixing DSA was not statistically different between the 3 groups and did not offer any prognostic value regarding graft survival. Performing biopsy for dnDSA could not be guided by the intensity criteria of IM LSAB assay. C3d-fixing DSA do not offer added value.