Non-HLA antibodies in transplantation: When do they matter?

Mary Carmelle Philogene, Annette M. Jackson

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations

Abstract

Purpose of review A growing interest in the contribution of non-human leukocyte antigens (non-HLA) antibodies to allograft rejection has led to the identification of multiple target antigens and investigation into the possible mechanisms of injury. Although several non-HLA antibody specificities have been identified, the largest cohorts studied are those detected using commercial assays. This review focuses on the phenotypes of injury associated with non-HLA antibody and defines in-vivo environmental characteristics that may be conducive to non-HLA antibody-mediated injury. Recent findings Mechanistic studies in animal models and clinical data suggest that an inflammatory environment, increased antigen expression, and development of neoantigens through posttranslational modifications contribute to non-HLA antibody development and their subsequent contribution to allograft injury. Furthermore, many reports show worse outcomes when HLA and non-HLA antibodies are present, suggesting possible interactions between these antibodies that lead to increased injury. Plasmapheresis and intravenous immunoglobulin are currently used to reduce HLA and non-HLA antibodies; however, therapeutic strategies targeting B cells and plasma cells simultaneously may lead to more durable antibody elimination. Summary Immune triggers that lead to non-HLA antibody formation are complex and poorly understood. The ability of non-HLA antibodies to mediate allograft injury may depend upon their specificity and affinity, density of the target antigen, and synergy with HLA antibodies.

Original languageEnglish (US)
Pages (from-to)427-432
Number of pages6
JournalCurrent opinion in organ transplantation
Volume21
Issue number4
DOIs
StatePublished - Aug 1 2016

Keywords

  • Allograft rejection
  • antibody-mediated rejection
  • non-HLA antibody
  • transplantation

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy

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