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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2019, Vol. 13 Issue (3) : 298-313
HLA and lung transplantation
Liya Ju1(), Caroline Suberbielle2, Xiaofan Li3, Nuala Mooney3,4, Dominique Charron1,2,4,5
1. HLA et Medecine, “Jean Dausset” Laboratory Network, Hôpital Saint-Louis, Paris, France
2. Laboratoire Histocompatibilité, Hôpital Saint-Louis, Paris, France
3. INSERM U1160, Hôpital Saint-Louis, Université Paris Diderot, Sorbonne Paris Cité, France
4. Labex Transplantex, Strasbourg, France
5. Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
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Lung transplantation is increasingly practiced for patients with end-stage lung disease. The successful outcome of solid organ transplantation today is severely impeded by the production of alloantibodies, mainly directed against the protein products of the HLA complex of the organ donor. While the association between antibody mediated rejection and allograft damage has been well established in renal and heart transplantation, it has not yet been well characterized in lung transplantation. This review addresses the question of HLA matching in lung transplantation and current knowledge of the allogenicity of different HLA class I and II antigens. The role of the antibody mediated immune response is discussed as well as the importance of pre-transplant or de novo post-transplant circulating antibodies. Finally, potential mechanisms, which may act individually or in combination, of antibody mediated damage to solid organ transplants are considered.

Keywords human leukocyte antigen class I and II      lung transplantation      mismatch      obliterans bronchiolitis      alloantibody      antibody mediated rejection     
Corresponding Authors: Liya Ju   
Just Accepted Date: 10 May 2018   Online First Date: 05 July 2018    Issue Date: 05 June 2019
 Cite this article:   
Liya Ju,Caroline Suberbielle,Xiaofan Li, et al. HLA and lung transplantation[J]. Front. Med., 2019, 13(3): 298-313.
HLA Loci Clinical outcome References
HLA-A, -B and-DR
Poor patient survival
Poor graft survival
Idiopathic pulmonary fibrosis
Obliterative bronchiolitis
Obliterative bronchiolitis
Poor graft survival
Poor patient survival
Poor graft survival
Obliterative bronchiolitis
Bronchopulmonary sequestration
Acute rejection
Obliterative bronchiolitis
Poor graft survival
Poor patient survival
Other loci (HLA-C, HLA-DQ)
Poor graft survival [24]
Tab.1  Effect of HLA mismatch (MM) on clinical outcome after lung transplantation
Fig.1  Presence of pre-existing anti HLA antibodies is a key factor in acute rejection after lung transplantation. The analysis of pre-existing anti-HLA antibodies is highly recommended before lung transplantation.
Methods Cross-match Screening Sensitivity Comment
CDC Yes Yes + Requires donor cells
FC Yes Yes ++ Requires donor cells
ELISA No Yes ++ Can be generic and specific
LUM No Yes +++/++ Can be generic and phenotypic
LUM SAB No Yes +++ Comprehensive allele specification
PRA No Yes ++ Generic test only
Tab.2  Testing methods of HLA antibodies in lung transplantation
Fig.2  De novo HLA-class I and-class II donor specific antibodies in the clinical outcome after lung transplantation. Both de novo DSA anti class I and class II can induce the poor survival of lung transplantation. De novo HLA-DQ DSA are more frequent than HLA-DR DSA.
Fig.3  Proposed mechanisms of anti HLA antibodies inducing lung rejection. Antibodies binding to “cells” can harm the allograft by several mechanisms: direct signaling in endothelial/epithelial cells may lead to increased recruitment of innate cells and/or leukocyte activation following increased production of soluble factors (and potentially by activation of adhesion molecules).
MFI≥500 Positive threshold
MFI= 500–2000 Weak
MFI= 2000– 8000* Moderate
MFI≥8000 Strong
* MFI≥5000 is considered as being clinically significant and a trigger for treatment [102].
Tab.3  Mean fluorescent intensity (MFI) of HLA-DSA in lung transplantation
Recommendations for lung transplantation
✓ Systematic testing of pre-existing anti HLA antibody in varity list of patients
✓ HLA typing during or after LTX to obtain the degree of mismatches in order to predict the clinical outcome risks
✓ Regularity detection of HLA antibody level of dnDSA could be outcome indicator
✓ Anti-DQ dnDSA may be biomarker of CLAD, BOS and AMR
Tab.4  Recommendations for lung transplantation
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