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Hum Immunol. 2017 Nov;78(11-12):692-698. doi: 10.1016/j.humimm.2017.09.004. Epub 2017 Oct 9.

Accelerated humoral renal allograft rejection due to HLA-C14 mediated allosensitization to HLA-Bw6.

Author information

1
Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: persaud@wustl.edu.
2
Department of Laboratories, Barnes-Jewish Hospital, St. Louis, MO 63110, USA.
3
Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
4
Division of Nephrology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
5
Division of Anatomic and Molecular Pathology, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
6
Division of Laboratory and Genomic Medicine, Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: cliu32@wustl.edu.

Abstract

OBJECTIVES:

To investigate immunological mechanisms underlying accelerated antibody-mediated rejection (AMR) of a living-related renal allograft in a patient with no detectable antibodies to donor human leukocyte antigens (HLA) in pre-transplant sera.

METHODS:

Pre- and post-transplant HLA antibody specificities were determined by single-antigen bead assay, and crossmatching was performed by flow cytometry- and complement-dependent cytotoxicity-based methods. Intermediate- and high-resolution HLA typing were performed by molecular methods.

RESULTS:

Pre-transplant patient serum reacted weakly against Bw6-positive beads; cytotoxicity and flow crossmatches were negative. The patient was mismatched for the donor antigens B62 and C10 (Bw6-positive). Following transplantation, strong antibody responses against B62, C10, and all Bw6-positive beads were detected. This reactivity was initially masked by complement interference, but became apparent at 1:20 dilution. High-resolution typing suggested that the anti-C16 antibody reactivity detected was an allele-specific response to donor C16:01 (Bw6-positive) but not recipient C16:02 (Bw6-negative). Alloimmunization likely occurred during pregnancy, during which HLA-C14 (Bw6-positive) was the only mismatched paternal HLA Class I allele.

CONCLUSIONS:

Sensitization to HLA-Bw6 via exposure to paternal HLA-C14 during pregnancy likely predisposed this patient to AMR. The case demonstrates the immunogenicity of HLA-C14-associated Bw6 epitopes in vivo and the clinical significance of low-level antibodies to HLA-Bw6.

KEYWORDS:

Alloimmunization; Crossmatch; HLA; Kidney; Transplantation

PMID:
29024716
DOI:
10.1016/j.humimm.2017.09.004
[Indexed for MEDLINE]

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