Influence of donor and recipient HLA locus mismatching on development of obliterative bronchiolitis after lung transplantation

Obliterative bronchiolitis (OB) after lung transplantation is the end result of multiple immunologic, virologic, genetic, and environmental effects on the transplanted lung. In this study, we first analyzed risk factors for OB in a single-center population of 152 lung transplant recipients. We then...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2001-02, Vol.163 (2), p.437-442
Main Authors: SCHULMAN, Larry L, WEINBERG, Alan D, MCGREGOR, Carlton C, SUCIU-FOCA, Nicole M, ITESCU, Silviu
Format: Article
Language:English
Subjects:
Adult
Biological and medical sciences
Bronchiolitis Obliterans - etiology
Cytomegalovirus Infections - etiology
Female
Graft Rejection - etiology
Histocompatibility Testing
HLA-A Antigens - genetics
HLA-DR Antigens - genetics
Humans
Lung Transplantation
Male
Medical sciences
Middle Aged
Pneumonia, Viral - etiology
Postoperative Complications - etiology
Risk Factors
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgery of the respiratory system
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Summary:Obliterative bronchiolitis (OB) after lung transplantation is the end result of multiple immunologic, virologic, genetic, and environmental effects on the transplanted lung. In this study, we first analyzed risk factors for OB in a single-center population of 152 lung transplant recipients. We then examined the influence of donor and recipient HLA mismatching on progression to OB, and on the identified risk factors for OB. The median time to onset of OB for the entire study population was 2.7 yr. The significant risk factors for OB by multivariate analyses were grade A2 or A3 acute rejection (p = 0.0126) and cytomegalovirus (CMV) pneumonitis (p = 0.0358). The only significant HLA risk factor for OB was mismatching at the HLA-A locus (p = 0.0144). On the basis of Cox proportional hazards modeling, a predictive formula was derived to estimate the risk of OB after lung transplantation. Although mismatching at the HLA-DR locus was a significant risk factor for CMV pneumonitis in recipients exposed to CMV before transplantation (p = 0.0199), and protected against acute rejection, it did not independently protect against OB. These results indicate that HLA mismatches between donors and recipients significantly influence the development of OB both directly, and indirectly, by influencing the major risk factors for OB.
ISSN:1073-449X
1535-4970
DOI:10.1164/ajrccm.163.2.2005031