Immunohistochemical study of HLA-G expression in lung transplant recipients.
Human leukocyte antigen-G (HLA-G), a nonclassical HLA class I protein, promotes immune tolerance of solid-organ allografts, yet its role in lung transplantation (LTx) is unknown. We examined the expression of HLA-G in lung allografts through immunohistochemistry by a cross-sectional study of 64 LTx recipients, classified into four groups (stable patients, acute rejection [AR], bronchiolitis obliterans syndrome [BOS] and symptomatic viral shedders). A marked expression of HLA-G in bronchial epithelial cells (BEC) was frequently observed in stable recipients (n = 18/35 [51%]), but not in patients with AR (n = 14) or with BOS (n = 8). HLA-G was also expressed by 4 of 7 symptomatic viral shedders. In addition, HLA-G-positive patients from the stable group (n = 35) experienced lower incidence of resistant AR and/or BOS during long-term follow-up, as compared with their HLA-G-negative counterparts. Finally, in vitro data showed that interferon-gamma, a cytokine present in lung allograft microenvironment, upregulated HLA-G mRNA and protein expression in primary cultured human BEC. We conclude that HLA-G expression in the bronchial epithelium of lung allograft is elevated in some LTx recipients in association with their functional stability, suggesting a potential role of HLA-G as a tolerance marker.
Brugière
O
O
Service de Pneumologie B et de Transplantation Pulmonaire, Centre Hospitalier Universitaire Bichat-Claude Bernard, Paris, France. olivier.brugiere@bch.aphp.fr
Thabut
G
G
Pretolani
M
M
Krawice-Radanne
I
I
Dill
C
C
Herbreteau
A
A
Poras
I
I
Moreau
P
P
Colombat
M
M
Danel
C
C
Dehoux
M
M
Fournier
M
M
Carosella
E D
ED
Rouas-Freiss
N
N
D000328:Adult; D001980:Bronchi / Q000378:metabolism; D001989:Bronchiolitis Obliterans / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006680:HLA Antigens / Q000096:biosynthesis*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000821:virology; D016040:Lung Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000378:metabolism; D012189:Retrospective Studies; D014777:Virus Diseases / Q000276:immunology
D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I