Respiratory Infections Following Lung Transplantation Leads to De Novo Development of Antibodies to Both Donor HLA and Lung Associated Self-Antigens and Increases the Risk for Bronchiolitis Obliterans Syndrome

K. George,¹ M. Gunasekaran,¹ M. Sharma,¹ F. Zhou,¹ A. Limaye,³ R. Hachem,² T. Mohanakumar.¹

¹Surgery, Washington Univ, St. Louis, MO
²Medicine, Washington Univ, St. Louis, MO
³Medicine, Univ Washington, Seattle, WA.

Meeting: 2015 American Transplant Congress

Abstract number: B202

Keywords: Antibodies, Graft failure, Lung infection, Lung transplantation

Session Information

Session Name: Poster Session B: Lung- All Topics

Session Type: Poster Session

Date: Sunday, May 3, 2015

Session Time: 5:30pm-6:30pm

Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Background: It is accepted that lower respiratory tract infections (LRI) post lung transplantation (LTx) are a risk factor for the development of Bronchiolitis Obliterans Syndrome (BOS). A significant correlation between the development of antibodies (Abs) to donor HLA and lung associated self-antigens (self-Ags) Collagen V (Col-V) and K-alpha 1 tubulin (Kα1T) in the development of BOS have been demonstrated.

Objective: To determine if LRI following LTx contributes to the development of donor specific antibodies (DSA) as well as Abs to lung associated self–Ags (Ka1T and Col-V), and to define its impact in the development of BOS.

Methods: Retrospective analysis (2000-2014) of patients 18 years or older with respiratory failure and underwent single or bilateral LTx were identified. Patients were stratified into history of prior LTI after transplantation and those without history of LRI. Ab concentrations were measured by ELISA. T-test was used to determine if a significant difference of DSAs, Abs to lung specific self-Ag, PRA values and development of BOS were seen amongst both groups. Bivariate analysis was used to determine if history of LTx and LRI were associated with development of DSA and Abs to self-Ag. Multivariable logistic regression was use to assess the combination of the presence of LRI, DSA, and Abs to self-Ag on the development of BOS.

Results: Sixty patients met our inclusion criteria. The etiologies necessitating LTx were chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and cystic fibrosis. On T-test analysis there was a significantly higher presence of DSA and Abs for self-Ag among those with history of LTI. Bivariate analysis documented a significant association among patients with LRI and the development of DSA and Abs to self-Ag. On multivariable logistic regression the combination of infection, DSA, and Abs to self-Ag was a significant predictor for development and/or progression of BOS.

Conclusion: LRI have been shown to be an independent risk factor for the development and progression of BOS. Our results for the first time demonstrate that LRI can also augment immune responses leading to de novo development of both DSA and self-Ags increasing the risk for development of BOS following human LTx.

To cite this abstract in AMA style:

George K, Gunasekaran M, Sharma M, Zhou F, Limaye A, Hachem R, Mohanakumar T. Respiratory Infections Following Lung Transplantation Leads to De Novo Development of Antibodies to Both Donor HLA and Lung Associated Self-Antigens and Increases the Risk for Bronchiolitis Obliterans Syndrome [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/respiratory-infections-following-lung-transplantation-leads-to-de-novo-development-of-antibodies-to-both-donor-hla-and-lung-associated-self-antigens-and-increases-the-risk-for-bronchiolitis-obliterans/. Accessed May 6, 2025.

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