title: IgG subclass profile among anti-Glutathione S-transferase T1 antibodies in post-transplant de novo immune hepatitis.
abstract: 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-GSTT 1 and IgG4-GSTT 1. 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-GSTT 1 /IgG4-GSTT 1 in samples from close to the time of diagnosis seemed to be important. The novel finding of abundant IgG4-GSTT 1 in liver transplantation is intriguing, but their possible role in pathogenesis of de novo IH remains unknown.
authors.affiliation: Department of Immunology, Instituto de Biomedicina de Sevilla (IBIS)/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Aguilera
authors.affiliation: Department of Immunology, Instituto de Biomedicina de Sevilla (IBIS)/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Martinez-Bravo
authors.affiliation: Digestive Diseases Service, Instituto de Biomedicina de Sevilla (IBIS)/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Sousa
authors.affiliation: Department of Immunology, Instituto de Biomedicina de Sevilla (IBIS)/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Antonio Jesús
authors.initials: AJ
authors.lastname: Pozo-Borrego
authors.affiliation: Department of Immunology, Instituto de Biomedicina de Sevilla (IBIS)/Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Núñez-Roldán
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D005982:Glutathione Transferase / Q000276:immunology*; D006084:Graft Rejection; D006085:Graft Survival; D019693:Hepatitis, Autoimmune / Q000097:blood / Q000209:etiology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification* / Q000276:immunology; D008107:Liver Diseases / Q000601:surgery*; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011379:Prognosis; D012307:Risk Factors; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase
keywords: GSTT1 mismatch; IgG4-related diseases; donor-specific immune response; liver allograft rejection