[Frontiers in Bioscience E4, 2378-2388, June 1, 2012]

Autoimmunity and lung transplantation

Ankit Bharat1, Thalachallour Mohanakumar2

1Department of Surgery and Cardiothoracic Surgery, Washington University School of Medicine, Campus Box 8109, 660 S. Euclid Avenue, St. Louis, MO 63110, 2Department of Pathology and Immunology, Washington University School of Medicine, Box 8109-3328 CSRB, 660 S. Euclid Avenue, St. Louis, MO 63110

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Clinical risk factors for BOS
3.1. Primary graft rejection
3.2. Acute cellular rejection
3.3. Humoral rejection
3.4. Respiratory viral infection
3.5. Gastroesophageal reflux
3.6. Autoimmunity
4. Pre-existing autoimmunity and its role in lung allograft rejection
4.1. Chronic inflammation in patients with end-stage lung disease can lead to autoimmunity
4.2. Pre-existing autoimmunity induces primary lung allograft dysfunction
5. De novo autoimmunity following lung transplantation
5.1. Lung transplantation provides an optimal environment for lung tissue specific autoimmunity
5.2. Autoimmunity in the pathogenesis of obliterative airway disease in animal models
6. De novo autoimmunity and its role in the pathogenesis of BOS
7. Alloimmunity and induction of de novo autoimmunity
8. Loss of Regulatory T cells and autoimmunity 9.Concluding remarks
10. References

1. ABSTRACT

Lung transplantation is a viable treatment option for a variety of end-stage lung diseases. Since the first successful human lung transplant about 20 years ago, tremendous progress has been made in this field. However, lung allografts have the poorest long term survival compared to other solid organs. The predominant reason for this is the development of chronic rejection, also known as bronchiolitis obliterans syndrome (BOS). Although the traditional view supports alloimmunity as the major cause of chronic rejection, emerging evidence reveals a complex interplay of multiple etiologies including perioperative stressors, inflammation, and autoimmunity along with alloimmunity. Identification of autoimmunity in the pathogenesis of BOS is an exciting recent finding in lung transplantation and promises to introduce novel strategies for future therapeutic interventions. In this review, we discuss recent studies and concepts related to the role of autoimmunity in the development of BOS.