Immunosuppressive activity of serum taken from a liver transplant recipient after withdrawal of immunosuppressants.
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.
Hsu
Li-Wen
LW
Liver Transplantation Program and Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Kaohsiung, Taiwan.
Goto
Shigeru
S
Nakano
Toshiaki
T
Lai
Chia-Yun
CY
Lin
Yu-Chun
YC
Kao
Ying-Hsien
YH
Chen
Shu-Hui
SH
Cheng
Yu-Fan
YF
Jawan
Bruno
B
Chiu
King-Wah
KW
Chen
Chao-Long
CL
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
D001798:Blood Proteins; D016207:Cytokines; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D003208:Concanavalin A; D015847:Interleukin-4; D007371:Interferon-gamma