Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics

Baeres, M; Herkel, Johannes; Czaja, Albert J.; Wies, Ingrid; Kanzler, Stephan; Cançado, Eduardo Luiz Rachid; Porta, Gilda; Nishioka, Mikio; Simon, Tracey G.; Daehnrich, Cornelia; Schlumberger, Wolfgang; Galle, Peter R.; Lohse, Ansgar W.

doi:10.1136/gut.51.2.259

Cited by 172 publications

(186 citation statements)

References 28 publications

(23 reference statements)

Supporting

Mentioning

153

Contrasting

Unclassified

Order By: Relevance

“…In addition, anti-soluble liver antigen (anti-SLA) antibodies serve as highly specific serological markers for AIH and exhibit 99% specificity for diagnosing this disease (30)(31)(32)(33). Anti-SLA antibodies have been found in 11%-22% of white North American and northern European adult patients with type 1 AIH and are common (18%-44% incidence) in children with type 1 and type 2 AIH (30,(34)(35)(36).…”

Section: Traf6δtec Mice Exhibit Classic Hallmarks Of Aih Such As Thementioning

confidence: 99%

Medullary thymic epithelial cell depletion leads to autoimmune hepatitis

Bonito

Aloman²,

Fiel³

et al. 2013

J. Clin. Invest.

View full text Add to dashboard Cite

TRAF6, an E3 ubiquitin protein ligase, plays a critical role in T cell tolerance by regulating medullary thymic epithelial cell (mTEC) development. mTECs regulate T cell tolerance by ectopically expressing self-antigens and eliminating autoreactive T cells in the thymus. Here we show that mice with mTEC depletion due to conditional deletion of Traf6 expression in murine thymic epithelial cells (Traf6ΔTEC mice) showed a surprisingly narrow spectrum of autoimmunity affecting the liver. The liver inflammation in Traf6ΔTEC mice exhibited all the histological and immunological characteristics of human autoimmune hepatitis (AIH). The role of T cells in AIH establishment was supported by intrahepatic T cell population changes and AIH development after transfer of liver T cells into immunodeficient mice. Despite a 50% reduction in natural Treg thymic output, peripheral tolerance in Traf6ΔTEC mice was normal, whereas compensatory T regulatory mechanisms were evident in the liver of these animals. These data indicate that mTECs exert a cell-autonomous role in central T cell tolerance and organ-specific autoimmunity, but play a redundant role in peripheral tolerance. These findings also demonstrate that Traf6ΔTEC mice are a relevant model with which to study the pathophysiology of AIH, as well as autoantigen-specific T cell responses and regulatory mechanisms underlying this disease.

show abstract

Section: Traf6δtec Mice Exhibit Classic Hallmarks Of Aih Such As Thementioning

confidence: 99%

Medullary thymic epithelial cell depletion leads to autoimmune hepatitis

Bonito

Aloman²,

Fiel³

et al. 2013

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Its presence identifies patients with a more severe disease and a worse outcome. It is also associated with HLA-DR3 (28,29) .Anti-LC1 is the second marker of AIH-2, detected in 24% to 32% of patients with anti-LKM1 and rarely as the only marker of AIH-2. It occurs mainly in young patients with an aggressive disease course with rapid progression to cirrhosis (30,31) .…”

Section: Diagnosismentioning

confidence: 99%

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

Bittencourt

Cançado

Couto

et al. 2015

Arq. Gastroenterol.

View full text Add to dashboard Cite

-In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology.

show abstract

“…Progress has been made in the definition of other autoantibodies frequently present in AIH but undetectable by IFL including antibodies against SLA/LP [51,[81][82][83][84][85] and ASGPR. Most of anti-SLA/LP positive patients are also positive for ANA, SMA or anti-LKM1, but occasionally anti-SLA is present in isolation and, in this case, its detection is of diagnostic importance [81,86] .…”

Section: Sla/lp and Asgprmentioning

confidence: 99%

“…Most of anti-SLA/LP positive patients are also positive for ANA, SMA or anti-LKM1, but occasionally anti-SLA is present in isolation and, in this case, its detection is of diagnostic importance [81,86] . The identification of the molecular target of anti-SLA/LP antibodies as the UGA serine tRNA-associated protein has led to the development of ELISA or dot-blot assays increasingly replacing the conventional inhibition ELISA originally used for anti-SLA antibody detection [51,83] . Recent studies investigating the exact role of this protein have shown that SLA/LP is a selenocysteine synthase but how the biosynthesis of selenocysteine may relate to the pathogenesis of AIH is not known [87] .…”

Section: Sla/lp and Asgprmentioning

confidence: 99%

“…Over the last decade there has been a steady increase in the use of the liver-related autoantibody tests to assist both diagnosis and clinical research into AiLD [55] . This increase has been attributed mainly to the introduction of molecularly based assays for the testing of antibodies to F-actin [70][71][72][73][74][75] , CYP2D6 [152] and SLA [83,122,153] in AIH, and for evaluating antibodies to sp100 and gp210 in PBC [92,[94][95][96]154] . Of concern, results for these antibody specificities may be promulgated by laboratories without authentication from externally or independently monitored quality assurance programmes (QAP).…”

Section: Emerging Issues: Diagnostic Accuracy Quality Assurance and mentioning

confidence: 99%

See 1 more Smart Citation

Autoimmune liver serology: Current diagnostic and clinical challenges

Bogdanos¹,

Invernizzi²,

Mackay³

et al. 2008

WJG

193

170

View full text Add to dashboard Cite

Liver-related autoantibodies are crucial for the correct diagnosis and classification of autoimmune liver diseases (AiLD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis variants in adults and children. AIH-1 is specified by anti-nuclear antibody (ANA) and smooth muscle antibody (SMA). AIH-2 is specified by antibody to liver kidney microsomal antigen type-1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1). SMA, ANA and anti-LKM antibodies can be present in de-novo AIH following liver transplantation. PBC is specified by antimitochondrial antibodies (AMA) reacting with enzymes of the 2-oxo-acid dehydrogenase complexes (chiefly pyruvate dehydrogenase complex E2 subunit) and disease-specific ANA mainly reacting with nuclear pore gp210 and nuclear body sp100. Sclerosing cholangitis presents as at least two variants, first the classical primary sclerosing cholangitis (PSC) mostly affecting adult men wherein the only (and nonspecific) reactivity is an atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA), also termed perinuclear anti-neutrophil nuclear antibodies (p-ANNA) and second the childhood disease called autoimmune sclerosing cholangitis (ASC) with serological features resembling those of type 1 AIH. Liver diagnostic serology is a fast-expanding area of investigation as new purified and recombinant autoantigens, and automated technologies such as ELISAs and bead assays, become available to complement (or even compete with) traditional immunofluorescence procedures. We survey for the first time global trends in quality assurance impacting as it does on (1) manufacturers/purveyors of kits and reagents, (2) diagnostic service laboratories that fulfill clinicians' requirements, and (3) the end-user, the physician providing patient care, who must properly interpret test results in the overall clinical context.

show abstract

Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics

Cited by 172 publications

References 28 publications

Medullary thymic epithelial cell depletion leads to autoimmune hepatitis

Medullary thymic epithelial cell depletion leads to autoimmune hepatitis

Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver

Autoimmune liver serology: Current diagnostic and clinical challenges

Contact Info

Product

Resources

About