1. De novo development of dsa and autoantibodies to lung associated self-antigens is associated with upregulation of transcription factor Zbtb7a: Role in chronic rejection following human lung transplantation.
- Author
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Nayak, Deepak, Zhou, Fangyu, Hachem, Ramsey, Kreisel, Daniel, and Mohanakumar, Thalachallour
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AUTOANTIBODIES , *LUNG transplantation , *TRANSPLANTATION of organs, tissues, etc. , *IMMUNOGLOBULINS , *HLA histocompatibility antigens , *MEDICAL screening - Abstract
Aim Administration of anti-MHC class I (H-2Kb) leads to induction of transcription factor Zinc finger and BTB domain containing 7A (Zbtb7a) leading to inflammatory cascade and chronic rejection in a murine obliterative airway disease model. Development of DSA and Abs to lung-associated self-antigens (K-alpla-1 Tubulin (K α 1T) and Collagen V (Col-V) are significant risk factors in development of bronchiolitis obliterans syndrome (BOS) following human lung transplantation (LTx). The current study focused on the role of Zbtb7a in development of BOS following human LTx. Methods We analyzed 25 LTx patients that developed BOS years after LTx as well as 10 stable LTx performed at Barnes-Jewish Washington University. Kinetics of Zbtb7a expression was studied in bronchoalveolar lavage (BAL) cells. Quantitative PCR analysis was performed to evaluate mRNA levels and data was compared with the DSA, autoantibody and immunosuppression. Results Increases in the Zbtb7a expression was observed in BAL cells collected at visits immediately prior to clinical BOS diagnosis compared with earlier visits. Zbtb7a expression was significantly ( p < 0.01) increased (150%) in pre-BOS BAL cells. On the contrary, stable patients did not demonstrate any change in Zbtb7a levels. All of the BOS+ patients had developed DSA and Abs to K α 1T and Col-V. Zbtb7a expression in 13 patients who received Ab directed therapy following DSA demonstrated significant reduction along with decrease in DSA and Abs to lung self-antigens. Therefore, Zbtb7a activation is an important inducer of the DSA and autoantibody. Conclusions Up regulation of Zbtb7a was positively associated with de novo DSA and Abs to lung-associated self-antigens. Ab directed therapy significantly reduced Zbtb7a expression. We propose that Zbtb7a may be used as a prognostic marker in evaluating Ab-induced inflammation in the lung as well as efficacy of Ab directed therapy following development of DSA. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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