Increase in Anti-Gal IgM Level is Associated With Early Graft Failure in Intraportal Porcine Islet Xenotransplantation.
10.3343/alm.2015.35.6.611
- Author:
Hee Jung KANG
1
;
Haneulnari LEE
;
Eun Mi PARK
;
Jong Min KIM
;
Jun Seop SHIN
;
Jung Sik KIM
;
Chung Gyu PARK
;
Sang Joon KIM
Author Information
1. Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea. kangheejung@hallym.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
Pig;
Non-human primate;
Islets;
Xenotransplantation;
Antibody;
Gal;
Early graft failure
- MeSH:
Animals;
Antibodies/blood/immunology;
Antigens, CD40/immunology;
Area Under Curve;
CD40 Ligand/immunology;
Disaccharides/*immunology;
Epidermal Growth Factor/blood;
Graft Rejection/*immunology;
Immunoglobulin G/blood;
Immunoglobulin M/*blood;
Immunosuppressive Agents/therapeutic use;
*Islets of Langerhans Transplantation;
Macaca mulatta;
ROC Curve;
Swine;
Transplantation, Heterologous
- From:Annals of Laboratory Medicine
2015;35(6):611-617
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
