Mounting evidence suggests that autoantibodies can develop during pulmonary disease progression before lung transplant, termed pre-existing autoantibodies, and may participate in allograft injury after transplantation. (CPD). The number of LTx performed annually in the US is usually rapidly increasing, and Astragaloside III the demand for donor lungs far exceeds availability. Despite the improved surgical techniques and post-transplant management, Astragaloside III the long-term survival has not significantly improved over the last decade and remains the lowest compared to other solid organ Tx (1). According to the International Society of Heart and Lung Transplantation (ISHLT) registry data, median survival after lung transplantation is usually 6.5 years, the worst amongst all solid organ transplantation, and is, in large part, the result of chronic allograft dysfunction (CLAD). Primary graft dysfunction (PGD) is usually a common early complication after LTx, and a major risk factor for development of CLAD. PGD occurs within the first 72 hours after transplantation and factors such as the recipients underlying lung disease, donor medical history, recipient/donor interaction, severity of post-Tx complications all play an integral part in determining LTx success. Arguably, organ transplantation was made possible through optimization of surgical techniques and subsequent manipulation of the immune system. Significant improvements have been made in controlling the recipients immune system post-transplant, largely by modulating T cell immune responses. While modulation of adaptive immunity is essential for graft survival other factors occurring earlier in the transplant process also play a role in graft injury. Initial immune-mediated graft injury occurs upon reperfusion, referred to as ischemia reperfusion injury (IRI). Following IRI, activation of innate and adaptive immune response drives targeted graft damage. This damage manifests as post-Tx complications such as PGD, acute rejection, and CLAD, all of which predispose to increased risk of mortality. The generally accepted model of immune-mediated graft damage proposes a feed-forward mechanism starting with donor graft injury, IRI-mediated immune activation and graft damage, thereby promoting subsequent adaptive immune activation and T cell specific graft damage. However, this model does not take into account the recipients lung specific pre-Tx Astragaloside III immune system. Patients with end-stage lung diseases, such as chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) often have autoimmunity, which is usually increasingly being recognized as a potential driver of graft injury post transplantation (2,3). The presence of a lung-specific autoreactive immune system pre-transplant may well predispose targeted attack of the donor lung upon implantation, and further exacerbate the alloimmune effector mechanisms activated post-transplant. Immune-mediated graft damage remains a major obstacle, and manipulation of the recipient immune system currently only occurs upon transplantation. Therefore, gaining a better understanding of the immune factors present within the LTx recipient prior to transplantation and how these factors contribute to shaping post-transplant graft outcomes can have a significant impact on the patient outcome. In this review, we will focus on the impact of pulmonary disease-associated autoantibodies and pulmonary disease-specific autoantibodies in LTx, and postulate on the clinical significance of autoantibodies identified in patients. == Pulmonary Diseases and Autoimmunity: Autoantibodies == Over the last 20 years, accumulated data proports a role for autoimmunity in pulmonary disease pathogenesis and progression of certain lung pathologies (4). How pulmonary disease autoimmunity arises and its influence on disease progression is not fully understood; however, it is generally accepted that autoimmune factors, Astragaloside III such as autoantibodies and autoreactive T cells, play critical roles in disease perpetuation. Autoantibodies are antibodies produced by the immune system with reactivity to self-antigens. Multiple mechanisms can render host molecules antigenic, interestingly, those same mechanisms can occur during or as a result of pulmonary disease onset. For example, environmental exposure to pollutants, such as those found in cigarette smoke, a major risk factor for COPD development, can drive mutations and post-translational modifications such as oxidation, carbonylation, Akt2 and citrullination to pulmonary peptides.
