Unexpected immunoresponse to Gal and APA antigens in diabetic type 1 patients receiving neonatal pig islets after 6 years.
Cotransplantation of porcine islets and Sertoli cells into preimplanted subcutaneous devices improve metabolic control in type 1 diabetic patients, and survive grafted for more than 4 years. We report here, further assessment of the endocrine and porcine nature of the surviving cells and the immune responses elicited toward Gal alpha(1,3)-Gal beta(1,4)-GlcNAc (Gal) antigen in patients who received a second and third transplants. No immunosuppressive drugs were administered. We were able to immunostain insulin- and glucagon-positive cells in all biopsies of patients and Sertoli cell markers in 60.9% of biopsies. Additionally, all biopsies tested, amplified the porcine COII gene. Patients demonstrated an increase in antipig antibodies in response to the first transplant with a decreasing response toward the second and third transplants. In all transplants, the IgG levels promptly returned to basal values after 3-4 months. The long-term survival of porcine cells and the reduced humoral immune response to multiple transplants indicate a form of tolerance. We have not been able to find CD25-positive cells, indicating that it is probably an immune accommodation of the graft.
Valdés-González
Rafael A
RA
Department of Surgery, Faculty of Medicine, UNAM, Mexico City, Mexico. rvaldes@xenomexico.org
Dorantes
Luis M
LM
Garibay
G Nayely
GN
Bracho-Blanchet
Eduardo
E
Dávila-Pérez
Roberto
R
Terán
Luis
L
Ormsby
Christopher E
CE
Ayala-Sumuano
Jorge-Tonatiuh
JT
Copeman
Laura
L
White
David J G
DJ
D000293:Adolescent; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D001706:Biopsy; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000601:surgery*; D005500:Follow-Up Studies; D006085:Graft Survival / Q000276:immunology; D006388:Hemagglutinins / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000145:classification / Q000276:immunology; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D012708:Sertoli Cells / Q000378:metabolism; D013552:Swine; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000276:immunology* / Q000473:pathology; D014312:Trisaccharides / Q000276:immunology*
D000906:Antibodies; D000941:Antigens; D006388:Hemagglutinins; D007074:Immunoglobulin G; D014312:Trisaccharides; C076569:alpha-galactosyl epitope