PMID- 20868794
OWN - NLM
STAT- MEDLINE
DCOM- 20101021
LR  - 20211020
IS  - 1552-6259 (Electronic)
IS  - 0003-4975 (Print)
IS  - 0003-4975 (Linking)
VI  - 90
IP  - 4
DP  - 2010 Oct
TI  - Antibodies to self-antigens predispose to primary lung allograft dysfunction and 
      chronic rejection.
PG  - 1094-101
LID - 10.1016/j.athoracsur.2010.06.009 [doi]
AB  - 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 
      antibodies whereas in the PGD negative group, only 14.6% had antibodies (p = 
      0.03). Antibody positive patients demonstrated high levels of proinflammatory 
      cytokines interleukin (IL)-1beta (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.
CI  - Copyright (c) 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All 
      rights reserved.
FAU - Bharat, Ankit
AU  - Bharat A
AD  - Department of Surgery, Division of Cardiothoracic Surgery, Washington University 
      School of Medicine, St. Louis, MO 63110, USA.
FAU - Saini, Deepti
AU  - Saini D
FAU - Steward, Nancy
AU  - Steward N
FAU - Hachem, Ramsey
AU  - Hachem R
FAU - Trulock, Elbert P
AU  - Trulock EP
FAU - Patterson, G Alexander
AU  - Patterson GA
FAU - Meyers, Bryan F
AU  - Meyers BF
FAU - Mohanakumar, Thalachallour
AU  - Mohanakumar T
LA  - eng
GR  - R01 HL056643/HL/NHLBI NIH HHS/United States
GR  - HL056643/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - Netherlands
TA  - Ann Thorac Surg
JT  - The Annals of thoracic surgery
JID - 15030100R
RN  - 0 (Autoantibodies)
RN  - 0 (Autoantigens)
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type V)
RN  - 0 (Tubulin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Autoantibodies/*immunology
MH  - Autoantigens/*immunology
MH  - Bronchiolitis Obliterans/*immunology
MH  - Chronic Disease
MH  - Collagen Type I/immunology
MH  - Collagen Type V/immunology
MH  - Female
MH  - Graft Rejection/immunology
MH  - Humans
MH  - Lung Transplantation/adverse effects/*immunology
MH  - Male
MH  - Middle Aged
MH  - Primary Graft Dysfunction/*immunology
MH  - Risk Factors
MH  - Tubulin/immunology
PMC - PMC3433047
MID - NIHMS401630
EDAT- 2010/09/28 06:00
MHDA- 2010/10/22 06:00
PMCR- 2012/09/04
CRDT- 2010/09/28 06:00
PHST- 2010/01/22 00:00 [received]
PHST- 2010/05/25 00:00 [revised]
PHST- 2010/06/01 00:00 [accepted]
PHST- 2010/09/28 06:00 [entrez]
PHST- 2010/09/28 06:00 [pubmed]
PHST- 2010/10/22 06:00 [medline]
PHST- 2012/09/04 00:00 [pmc-release]
AID - S0003-4975(10)01295-6 [pii]
AID - 10.1016/j.athoracsur.2010.06.009 [doi]
PST - ppublish
SO  - Ann Thorac Surg. 2010 Oct;90(4):1094-101. doi: 10.1016/j.athoracsur.2010.06.009.