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Antibodies to self-antigens predispose to primary lung allograft dysfunction and chronic rejection.
Ann Thorac Surg. 2010 Oct; 90(4):1094-101.AT

Abstract

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)-1β (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.

Authors+Show Affiliations

Department of Surgery, Division of Cardiothoracic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

20868794

Citation

Bharat, Ankit, et al. "Antibodies to Self-antigens Predispose to Primary Lung Allograft Dysfunction and Chronic Rejection." The Annals of Thoracic Surgery, vol. 90, no. 4, 2010, pp. 1094-101.
Bharat A, Saini D, Steward N, et al. Antibodies to self-antigens predispose to primary lung allograft dysfunction and chronic rejection. Ann Thorac Surg. 2010;90(4):1094-101.
Bharat, A., Saini, D., Steward, N., Hachem, R., Trulock, E. P., Patterson, G. A., Meyers, B. F., & Mohanakumar, T. (2010). Antibodies to self-antigens predispose to primary lung allograft dysfunction and chronic rejection. The Annals of Thoracic Surgery, 90(4), 1094-101. https://doi.org/10.1016/j.athoracsur.2010.06.009
Bharat A, et al. Antibodies to Self-antigens Predispose to Primary Lung Allograft Dysfunction and Chronic Rejection. Ann Thorac Surg. 2010;90(4):1094-101. PubMed PMID: 20868794.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Antibodies to self-antigens predispose to primary lung allograft dysfunction and chronic rejection. AU - Bharat,Ankit, AU - Saini,Deepti, AU - Steward,Nancy, AU - Hachem,Ramsey, AU - Trulock,Elbert P, AU - Patterson,G Alexander, AU - Meyers,Bryan F, AU - Mohanakumar,Thalachallour, PY - 2010/01/22/received PY - 2010/05/25/revised PY - 2010/06/01/accepted PY - 2010/9/28/entrez PY - 2010/9/28/pubmed PY - 2010/10/22/medline SP - 1094 EP - 101 JF - The Annals of thoracic surgery JO - Ann. Thorac. Surg. VL - 90 IS - 4 N2 - 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)-1β (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. SN - 1552-6259 UR - https://www.unboundmedicine.com/medline/citation/20868794/Antibodies_to_self_antigens_predispose_to_primary_lung_allograft_dysfunction_and_chronic_rejection_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0003-4975(10)01295-6 DB - PRIME DP - Unbound Medicine ER -