title: Immunosuppressive activity of serum taken from a liver transplant recipient after withdrawal of immunosuppressants.
abstract: In orthotopic liver transplantation (OLT), tolerance is induced in a certain combination of donors and a recipient in rats and, in some clinical cases, rejection has not occurred in OLT patients after weaning off immunosuppression. However, this mechanism has not yet been elucidated. Among our cases of liver transplantation (LTx), one OLT patient (Patient A) has not required immunosuppressive drugs for the last 5 years, following post-transplant lymphoproliferative disease (PTLD). This patient's serum interleukin-2 levels were undetectable following withdrawal of immunosuppressants. The same serum taken after discontinuing the immunosuppressants inhibited concanavalin A blast cultured cells and up-regulated the IL-4/IFN-gamma gene expression ratio. These results suggested that other proteins were induced following withdrawal of immunosuppressants. Proteomic assay demonstrated 12 differentiated spots exclusive to this patient where immunosuppressants have been discontinued. Haptoglobin, found to have immunosuppressive activity in vitro, may play an important role in the maintenance of drug-free tolerance as a natural immunological suppressor after cessation of immunosuppression. Proteomic analysis will allow us to develop a novel weaning protocol for patients on long-term immunosuppression to avoid major immunosuppressant-related complications.
authors.affiliation: Liver Transplantation Program and Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
authors.forename: Li-Wen
authors.initials: LW
authors.lastname: Hsu
authors.forename: Shigeru
authors.initials: S
authors.lastname: Goto
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Nakano
authors.forename: Chia-Yun
authors.initials: CY
authors.lastname: Lai
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.forename: Ying-Hsien
authors.initials: YH
authors.lastname: Kao
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Chen
authors.forename: Yu-Fan
authors.initials: YF
authors.lastname: Cheng
authors.forename: Bruno
authors.initials: B
authors.lastname: Jawan
authors.forename: King-Wah
authors.initials: KW
authors.lastname: Chiu
authors.forename: Chao-Long
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D001798:Blood Proteins / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000097:blood; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D016031:Liver Transplantation; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D040901:Proteomics; D023001:Transplantation Tolerance; D015854:Up-Regulation; D028761:Withholding Treatment
chemical_list: D001798:Blood Proteins; D016207:Cytokines; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D003208:Concanavalin A; D015847:Interleukin-4; D007371:Interferon-gamma