title: Dysregulated MicroRNA Expression and Chronic Lung Allograft Rejection in Recipients With Antibodies to Donor HLA.
abstract: The pathogenesis of chronic rejection, Bronchiolitis Obliterans Syndrome (BOS) following lung transplantation (LT) is poorly understood. We hypothesized that development of antibodies to HLA (DSA) is associated with dysregulation of microRNA (miRNA) that predisposes BOS. Towards this, miRNA profiling of mononuclear cells from 10 stable LT (DSA(-) BOS(-) ), 10 LT with DSA(+) BOS(-) (DSA group) and 10 LT with DSA(+) BOS(+) (BOS group) were performed. Prediction by mirPath indicated that differential miRNAs in DSA(+) BOS(-) compared to stable are significantly up-regulated (relative fold >2, p < 0.05) for TGF-β and B cell receptor signal pathways. A total of seventy-four miRNAs were up-regulated and six miRNAs were down regulated in LT with DSA(+) BOS(+) when compared to stable (relative fold >2, p < 0.05). There was also significant enrichment of cell cycle and gap junction pathways. An inverse correlation between expression of two key miRNAs and their target genes were observed: miR-369-5p and miR-548d were down regulated in DSA(+) LT while their gene targets in TGF-β signal pathways were up-regulated. In addition, miR-628-5p and miR-134 were down regulated and their target genes (B cell development) were up-regulated. Therefore, we conclude that alloimmunity induced changes in miRNAs affecting the TGF-β and B cell receptor signal pathways play important roles in BOS development.
authors: Department of Surgery, Washington University School of Medicine, St. Louis, MO.
authors: Z
authors: Z
authors: Xu
authors: Department of Surgery, Washington University School of Medicine, St. Louis, MO.
authors: D
authors: D
authors: Nayak
authors: Department of Genetics, Washington University School of Medicine, St. Louis, MO.
authors: W
authors: W
authors: Yang
authors: Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors: G
authors: G
authors: Baskaran
authors: Department of Surgery, Washington University School of Medicine, St. Louis, MO.
authors: S
authors: S
authors: Ramachandran
authors: Department of Surgery, Washington University School of Medicine, St. Louis, MO.
authors: N
authors: N
authors: Sarma
authors: Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors: A
authors: A
authors: Aloush
authors: Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors: E
authors: E
authors: Trulock
authors: Department of Medicine, Washington University School of Medicine, St. Louis, MO.
authors: R
authors: R
authors: Hachem
authors: Department of Surgery, Washington University School of Medicine, St. Louis, MO.
authors: G A
authors: GA
authors: Patterson
authors: Department of Surgery, Washington University School of Medicine, St. Louis, MO.|Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
authors: T
authors: T
authors: Mohanakumar
mesh_terms: D064591:Allografts; D001989:Bronchiolitis Obliterans / Q000150:complications / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006084:Graft Rejection / Q000209:etiology* / Q000473:pathology; D006085:Graft Survival; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D016040:Lung Transplantation; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D014019:Tissue Donors; D016212:Transforming Growth Factor beta / Q000235:genetics; D066027:Transplant Recipients
chemical_list: D006680:HLA Antigens; D007518:Isoantibodies; D035683:MicroRNAs; D016212:Transforming Growth Factor beta
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