Research Topic

A Hill of Needs: Current State of the Art and Knowledge Gaps for Non-HLA Antibodies in Allograft Transplantation

About this Research Topic

Antibodies recognizing the highly polymorphic human leukocyte antigen (HLA) on allograft endothelium of transplanted organs contribute to rejection and graft loss. However, antigens other than HLA, termed redundantly as non-HLA antigens, auto-antigens or anti-endothelial cell antigens, are also being considered as targets of humoral immune allograft injury. Association with poor allograft outcomes (rejection and graft loss), and synergistic or additive effects in the context of HLA DSA predominate the themes emerging from the body of clinical studies in pre- and post-transplant patients. Mechanisms underlying the immune context for non-HLA antibody production and antibody effector functions, as well as diagnostic criteria for allograft pathology remain open to further discovery. Current clinical laboratory tests for non-HLA antibodies range from fairly non-specific and insensitive to high-throughput multiplex platforms offering significant sensitivity and specificity, but with limitations (lack of standardized reference sera and established quality control/assurance) contributing to weak consensus for clinical utility of non-HLA antibody tests.

The goal of this research topic is to present the current rational and state of the art for testing transplant patients for non-HLA antibodies. We explore the strengths and limitations of various testing platforms, association of non-HLA antibodies with allograft pathology and transplant outcomes, and key advances and knowledge gaps in our understanding of the mechanisms underlying non-HLA antibody production and effector function.

We welcome submissions of Review, Mini-Review, Opinion, as well as Original Research articles focusing on, but now strictly limited to the following topics that will further define the clinical utility of non-HLA antibody testing in this patient population:
1) Non-HLA Antibody Identification- current clinical laboratory methods for antibody detection; state of the art- Luminex detection assays; assay strengths and gaps; issues of regulatory and quality assurance; methods for further antibody discovery
2) Clinical utility of Non-HLA antibody tests- testing of pre-transplant vs post-transplant patients for non-HLA antibodies; longitudinal non-HLA antibody patterns; graft pathology and transplant outcomes in the context of non-HLA antibodies alone or in context with HLA donor specific antibodies; synergistic effects with non-HLA and donor specific antibodies
3) Non-HLA antibody production and Immune Context- mechanisms of non-HLA antibody production (immune triggers; autoimmune disease; vesicles; ischemia reperfusion; infection; healthy individuals vs autoimmune or other diseases that underly native organ failure and need for transplant), non-HLA alloimmunity vs autoimmunity
4) Non-HLA Antibody Effector Function- current knowledge of affinity; strength; antigen expression; antibody expression patterns; association with cytokine profiles or immune cell repertoire.

Dr. Hickey receives a share of royalty received on sales of the Lifecodes Non-HLA Antibody kit, managed by UCLA. The other Topic Editors declare no competing interests with regards to the Research Topic


Keywords: Non-HLA antibody, allograft transplantation, sensitization, auto-antibody, anti-endothelial cell antibody, Luminex detection, high-throughput multiplex, allograft pathology, antibody effector mechanism, antibody production


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Antibodies recognizing the highly polymorphic human leukocyte antigen (HLA) on allograft endothelium of transplanted organs contribute to rejection and graft loss. However, antigens other than HLA, termed redundantly as non-HLA antigens, auto-antigens or anti-endothelial cell antigens, are also being considered as targets of humoral immune allograft injury. Association with poor allograft outcomes (rejection and graft loss), and synergistic or additive effects in the context of HLA DSA predominate the themes emerging from the body of clinical studies in pre- and post-transplant patients. Mechanisms underlying the immune context for non-HLA antibody production and antibody effector functions, as well as diagnostic criteria for allograft pathology remain open to further discovery. Current clinical laboratory tests for non-HLA antibodies range from fairly non-specific and insensitive to high-throughput multiplex platforms offering significant sensitivity and specificity, but with limitations (lack of standardized reference sera and established quality control/assurance) contributing to weak consensus for clinical utility of non-HLA antibody tests.

The goal of this research topic is to present the current rational and state of the art for testing transplant patients for non-HLA antibodies. We explore the strengths and limitations of various testing platforms, association of non-HLA antibodies with allograft pathology and transplant outcomes, and key advances and knowledge gaps in our understanding of the mechanisms underlying non-HLA antibody production and effector function.

We welcome submissions of Review, Mini-Review, Opinion, as well as Original Research articles focusing on, but now strictly limited to the following topics that will further define the clinical utility of non-HLA antibody testing in this patient population:
1) Non-HLA Antibody Identification- current clinical laboratory methods for antibody detection; state of the art- Luminex detection assays; assay strengths and gaps; issues of regulatory and quality assurance; methods for further antibody discovery
2) Clinical utility of Non-HLA antibody tests- testing of pre-transplant vs post-transplant patients for non-HLA antibodies; longitudinal non-HLA antibody patterns; graft pathology and transplant outcomes in the context of non-HLA antibodies alone or in context with HLA donor specific antibodies; synergistic effects with non-HLA and donor specific antibodies
3) Non-HLA antibody production and Immune Context- mechanisms of non-HLA antibody production (immune triggers; autoimmune disease; vesicles; ischemia reperfusion; infection; healthy individuals vs autoimmune or other diseases that underly native organ failure and need for transplant), non-HLA alloimmunity vs autoimmunity
4) Non-HLA Antibody Effector Function- current knowledge of affinity; strength; antigen expression; antibody expression patterns; association with cytokine profiles or immune cell repertoire.

Dr. Hickey receives a share of royalty received on sales of the Lifecodes Non-HLA Antibody kit, managed by UCLA. The other Topic Editors declare no competing interests with regards to the Research Topic


Keywords: Non-HLA antibody, allograft transplantation, sensitization, auto-antibody, anti-endothelial cell antibody, Luminex detection, high-throughput multiplex, allograft pathology, antibody effector mechanism, antibody production


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

31 August 2021 Abstract
29 December 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

31 August 2021 Abstract
29 December 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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