Antibodies to conformational epitopes of soluble liver antigen define a severe form of autoimmune liver disease.

Prevalence and clinical relevance of antibodies to soluble liver antigen (tRNP((Ser)Sec)/SLA) in autoimmune hepatitis (AIH) have been investigated using partially purified or prokaryotically expressed antigen. The aim of this study was to improve the detection of anti-tRNP((Ser)Sec)/SLA by establishing an immunoassay that was able to identify antibodies directed to conformational epitopes and to investigate the clinical implication of this autoantibody in autoimmune liver disease. By using eukaryotically expressed tRNP((Ser)Sec)/SLA as target in a radioligand assay (RLA), 81 patients with autoimmune liver disease (AILD) (33 type 1 AIH, 31 type 2 AIH, and 17 autoimmune sclerosing cholantitis [ASC]), 147 pathologic, and 56 healthy controls were investigated. RLA results were compared with those obtained using a commercial enzyme-linked immunosorbent assay (ELISA) and immunoblot. Reactivity to tRNP((Ser)Sec)/SLA was present in 58% of patients with type 1 and type 2 AIH, 41% with ASC, but in only 3 pathologic controls. RLA was similarly disease-specific but remarkably more sensitive than ELISA and immunoblot. A prospective study showed that anti-tRNP((Ser)Sec)/SLA-positive patients run a severe clinical course, having worse histology, needing longer to achieve remission, relapsing and requiring liver transplantation or dying more frequently than anti-tRNP((Ser)Sec)/SLA negative patients. Anti-tRNP((Ser)Sec)/SLA production was favored by the possession of DR3 and A1-B8-DR3 in AIH type 1 and ASC, and prevented by the possession of A2 in all 3 types of AILD, particularly in type 2 AIH. In conclusion, anticonformational tRNP((Ser)Sec)/SLA reactivity is frequent in type 1 and type 2 AIH and ASC, defining patients with a worse prognosis.
AuthorsYun Ma, Manabu Okamoto, Mark G Thomas, Dimitrios P Bogdanos, Agnel R Lopes, Bernard Portmann, James Underhill, Ralf Dürr, Giorgina Mieli-Vergani, Diego Vergani
JournalHepatology (Baltimore, Md.) (Hepatology) Vol. 35 Issue 3 Pg. 658-64 (Mar 2002) ISSN: 0270-9139 [Print] United States
PMID11870381 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Autoantibodies
  • Autoantigens
  • Epitopes
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • liver antigen LA-1
  • Autoantibodies (analysis)
  • Autoantigens (immunology)
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes
  • Hepatitis, Autoimmune (diagnosis, immunology)
  • Histocompatibility Antigens Class I (analysis)
  • Histocompatibility Antigens Class II (analysis)
  • Humans
  • Immunoblotting
  • Prospective Studies
  • Radioligand Assay

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: