Antibodies to Self-Antigens Predispose to Primary Lung Allograft Dysfunction and Chronic Rejection

被引:103
作者
Bharat, Ankit
Saini, Deepti
Steward, Nancy
Hachem, Ramsey
Trulock, Elbert P.
Patterson, Alexander
Meyers, Bryan F.
Mohanakumar, Thalachallour [1 ]
机构
[1] Washington Univ, Sch Med, Dept Surg,Div Pulm Med, Div Cardiothorac Surg,Dept Internal Med, St Louis, MO 63110 USA
关键词
BRONCHIOLITIS OBLITERANS SYNDROME; PRIMARY GRAFT DYSFUNCTION; V COLLAGEN; TRANSPLANTATION; IMMUNITY; INJURY; HLA;
D O I
10.1016/j.athoracsur.2010.06.009
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background. Primary graft dysfunction (PGD) is a known risk factor for bronchiolitis obliterans syndrome (BOS) after lung transplantation. Here, we report that preformed antibodies to self-antigens increase PGD risk and promote BOS. Methods. Adult lung transplant recipients (n = 142) were included in the study. Primary graft dysfunction and BOS were diagnosed based on International Society for Heart and Lung Transplantation guidelines. Antibodies to self-antigens k-alpha-1 tubulin, collagen type V, and collagen I were quantitated using standardized enzyme-linked immunosorbent assays, and cytokines were analyzed using Luminex immunoassays (Biosource International, Camirillo, CA). Human leukocyte antigen (HLA) antibodies were measured using Flow-PRA (One Lambda, Canoga Park, CA). Results. Lung transplant recipients with pretransplant antibodies to self-antigens had increased risk of PGD (odds ratio 3.09, 95% confidence interval: 1.2 to 8.1, p = 0.02) compared with recipients without. Conversely, in patients with PGD, 34.7% were positive for pretransplant antibodieswhereas in the PGD negative group, only 14.6% had antibodies (p = 0.03). Antibody positive patients demonstrated high levels of proinflammatory cytokines interleukin (IL)-1 beta (2.1-fold increase), IL-2 (3.0), IL-12 (2.5), IL-15 (3.0), and chemokines interferon-inducible protein-10 (3.9) and monocyte chemotactic protein-1 (3.1; p < 0.01 for all). On 5-year follow-up, patients without antibodies showed greater freedom from development of HLA antibodies compared with patients who had antibodies (class I: 67% versus 38%, p = 0.001; class II: 71% versus 41%, p < 0.001). Patients with pretransplant antibodies were found to have an independent relative risk of 2.3 (95% confidence interval: 1.7 to 4.5, p = 0.009) for developing BOS. Conclusions. Presence of antibodies to self-antigens pretransplant increases the risk of PGD immediately after transplant period and BOS on long-term follow-up. Primary graft dysfunction is associated with an inflammatory cascade that augments the alloimmune (anti-HLA) response that predisposes to BOS. (Ann Thorac Surg 2010;90:1094-101) (c) 2010 by The Society of Thoracic Surgeons
引用
收藏
页码:1094 / 1100
页数:7
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