Increase in anti-Gal IgM level is associated with early graft failure in intraportal porcine islet xenotransplantation.
BACKGROUND
Anti-Gal is a major antibody induced in non-human primates (NHPs) after xenotransplantation. To understand the mechanism of graft rejection, we investigated the association between anti-Gal responses and graft failure in NHP recipients of porcine islet transplantation (PITx).


METHODS
Intraportal PITx was performed in 35 diabetic NHPs, and graft function was monitored. Early graft failure (EGF) was defined as loss of graft function within a month after PITx. Seven, 19, nine NHPs received immunosuppression (IS) without CD40 pathway blockade (Group I), with anti-CD154 (Group II), and with anti-CD40 (Group III), respectively. The anti-Gal levels on day 0 and day 7 of PITx were measured by ELISA.


RESULTS
The frequency of EGF was significantly lower in Group II (26.3%) than in Group I (100%, P=0.0012) and Group III (77.8%, P=0.0166). While levels of anti-Gal IgG in Group I and anti-Gal IgM in Group III increased on day 7 compared with day 0 (P=0.0156 and 0.0273), there was no increase in either on day 7 in Group II. The ratio of anti-Gal IgM or IgG level on day 7 to that on day 0 (Ratio7/0) was significantly higher in recipients with EGF than without EGF (P=0.0009 and 0.0027). ROC curve analysis of anti-Gal IgM Ratio7/0 revealed an area under the curve of 0.789 (P=0.0003).


CONCLUSIONS
IS with anti-CD154 suppressed anti-Gal responses and prevented EGF in PITx. Anti-Gal IgM Ratio7/0, being associated with EGF, is a predictive marker for EGF.
Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea. kangheejung@hallym.ac.kr.
Hee Jung
HJ
Kang
Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea.
Haneulnari
H
Lee
Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea.
Eun Mi
EM
Park
Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, Korea.
Jong Min
JM
Kim
Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, Korea.
Jun Seop
JS
Shin
Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, Korea.
Jung Sik
JS
Kim
Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, Korea.|Department of Microbiology and Immunology, Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea.
Chung Gyu
CG
Park
Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul, Korea.
Sang Joon
SJ
Kim
D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D019540:Area Under Curve; D019013:CD40 Antigens / Q000276:immunology; D023201:CD40 Ligand / Q000276:immunology; D004187:Disaccharides / Q000276:immunology*; D004815:Epidermal Growth Factor / Q000097:blood; D006084:Graft Rejection / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016381:Islets of Langerhans Transplantation; D008253:Macaca mulatta; D012372:ROC Curve; D013552:Swine; D014183:Transplantation, Heterologous
D000906:Antibodies; D019013:CD40 Antigens; D004187:Disaccharides; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; C055075:galactosyl-(1-3)galactose; D023201:CD40 Ligand; D004815:Epidermal Growth Factor
Antibody; Early graft failure; Gal; Islets; Non-human primate; Pig; Xenotransplantation