IgG subclass profile among anti-Glutathione S-transferase T1 antibodies in post-transplant de novo immune hepatitis

• Published in: Clinical transplantation Vol. 30; no. 3; pp. 210 - 217
• Main Authors: Aguilera, Isabel, Martinez-Bravo, Maria José, Sousa, Jose Manuel, Pozo-Borrego, Antonio Jesús, Núñez-Roldán, Antonio
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.03.2016
• Subjects: Adolescent; Adult; Aged; Autoantibodies - blood; donor-specific immune response; Female; Follow-Up Studies; Glutathione Transferase - immunology; Graft Rejection; Graft Survival; GSTT1 mismatch; Hepatitis, Autoimmune - blood; Hepatitis, Autoimmune - etiology; Humans; IgG4-related diseases; Immunoglobulin G - blood; Immunoglobulin G - classification; Immunoglobulin G - immunology; liver allograft rejection; Liver Diseases - surgery; Liver Transplantation - adverse effects; Male; Middle Aged; Postoperative Complications; Prognosis; Risk Factors; Tissue Donors; Young Adult; GSTT1 mismatch; IgG4-related diseases; donor-specific immune response; liver allograft rejection
• ISSN: 0902-0063; 1399-0012
• DOI: 10.1111/ctr.12675

Although the pathogenic pathways leading to de novo immune hepatitis (IH) are not completely understood, we have shown strong evidences of an antidonor response against Glutathione S‐transferase T1 (GSTT1), an antigen exclusively expressed in the donor liver. The first sign of this process is the production of GSTT1 antibodies that, in 25% of the cases, will precede de novo IH. Because the presence of the antibodies is not sufficient to trigger the disease, we aimed to study GSTT1 IgG subclasses in a group of 18 liver transplant patients, 12 that developed de novo IH and 6 that remained free of disease. Surprisingly, the predominant subclasses were IgG1‐GSTT1 and IgG4‐GSTT1. The presence of IgG4‐expressing plasma cells was also investigated in 10 available liver biopsies. Six biopsies coinciding with diagnosis showed a mean value of 32.8 IgG4+ plasma cells/hpf vs. 5.55 in patients without the disease. We have not found a distinctive GSTT1‐IgG profile in patients with de novo IH, but the ratio IgG1‐GSTT1/IgG4‐GSTT1 in samples from close to the time of diagnosis seemed to be important. The novel finding of abundant IgG4‐GSTT1 in liver transplantation is intriguing, but their possible role in pathogenesis of de novo IH remains unknown.