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Ansgar W. Lohse - One of the best experts on this subject based on the ideXlab platform.

  • identification of cd4 t cell epitopes in soluble Liver Antigen Liver pancreas autoAntigen in autoimmune hepatitis
    Gastroenterology, 2008
    Co-Authors: Heiko Mix, Ansgar W. Lohse, Johannes Herkel, Robert Thimme, Golo Ahlenstiel, Eui-cheol Shin, Chella S. David, Christina Weilernormann
    Abstract:

    Background & Aims Autoimmune hepatitis (AIH) is a chronic inflammatory Liver disease associated with autoantibodies and Liver-infiltrating lymphocytes. Although autoantibodies are tested routinely to diagnose and classify AIH, Liver-infiltrating lymphocytes are regarded as the primary factor for disease pathogenesis. The purpose of this study was to identify and characterize autoAntigenic peptides within human AIH-specific soluble Liver Antigen/Liver pancreas Antigen (SLA/LP) that are targeted by CD4 + T cells and restricted by the disease susceptibility gene HLA-DRB1*0301. Methods HLA-DRB1*0301 transgenic mice were immunized with SLA/LP. Antibody and T-cell responses were analyzed with SLA/LP-overlapping peptides in enzyme immunoassay, proliferation, and enzyme-linked immunospot (ELISpot) assays. Minimal optimal T-cell epitopes were identified, characterized with cloned T-cell hybridomas, and confirmed in tetramer and ELISpot assays with AIH patients' peripheral blood mononuclear cells. Results All mice developed SLA/LP-specific IgG1/IgG2a antibodies against the same SLA/LP peptides as human beings. T cells targeted several peptides within SLA/LP, 2 of which were DR3-restricted and one overlapped the sequence recognized by human autoantibodies. Minimal optimal epitopes were mapped, DRB1*0301/epitope-tetramers were generated, and the frequency and function of HLA-DRB1*0301-restricted autoAntigen-specific T cells in AIH patients were analyzed with tetramer and interferon-γ ELISpot assays. Conclusions This study identified T-cell epitopes within SLA/LP, restricted by the disease susceptibility gene DRB1*0301 and in close proximity to the human autoantibody epitope. These results and the generated reagents now provide the opportunity to directly monitor autoreactive T cells in AIH patients in clinical studies.

  • Identification of CD4 T Cell Epitopes in Soluble Liver Antigen / Liver Pancreas AutoAntigen in Autoimmune Hepatitis
    Gastroenterology, 2008
    Co-Authors: Heiko Mix, Ansgar W. Lohse, Johannes Herkel, Christina Weiler-normann, Robert Thimme, Golo Ahlenstiel, Eui-cheol Shin, Chella S. David, Barbara Rehermann
    Abstract:

    Background & Aims Autoimmune hepatitis (AIH) is a chronic inflammatory Liver disease associated with autoantibodies and Liver-infiltrating lymphocytes. Although autoantibodies are tested routinely to diagnose and classify AIH, Liver-infiltrating lymphocytes are regarded as the primary factor for disease pathogenesis. The purpose of this study was to identify and characterize autoAntigenic peptides within human AIH-specific soluble Liver Antigen/Liver pancreas Antigen (SLA/LP) that are targeted by CD4 + T cells and restricted by the disease susceptibility gene HLA-DRB1*0301. Methods HLA-DRB1*0301 transgenic mice were immunized with SLA/LP. Antibody and T-cell responses were analyzed with SLA/LP-overlapping peptides in enzyme immunoassay, proliferation, and enzyme-linked immunospot (ELISpot) assays. Minimal optimal T-cell epitopes were identified, characterized with cloned T-cell hybridomas, and confirmed in tetramer and ELISpot assays with AIH patients' peripheral blood mononuclear cells. Results All mice developed SLA/LP-specific IgG1/IgG2a antibodies against the same SLA/LP peptides as human beings. T cells targeted several peptides within SLA/LP, 2 of which were DR3-restricted and one overlapped the sequence recognized by human autoantibodies. Minimal optimal epitopes were mapped, DRB1*0301/epitope-tetramers were generated, and the frequency and function of HLA-DRB1*0301-restricted autoAntigen-specific T cells in AIH patients were analyzed with tetramer and interferon-γ ELISpot assays. Conclusions This study identified T-cell epitopes within SLA/LP, restricted by the disease susceptibility gene DRB1*0301 and in close proximity to the human autoantibody epitope. These results and the generated reagents now provide the opportunity to directly monitor autoreactive T cells in AIH patients in clinical studies.

  • Selenocysteine, soluble Liver Antigen/ Liver-pancreas, and autoimmune hepatitis
    Hepatology (Baltimore Md.), 2007
    Co-Authors: Johannes Herkel, Michael P. Manns, Ansgar W. Lohse
    Abstract:

    The trace element selenium is found in proteins as selenocysteine (Sec), the 21st amino acid to participate in ribosome-mediated translation. The substrate for ribosomal protein synthesis is selenocysteinyl-tRNASec. Its biosynthesis from seryl-tRNASec has been established for bacteria, but the mechanism of conversion from Ser-tRNASec remained unresolved for archaea and eukarya. Here, we provide evidence for a different route present in these domains of life that requires the tRNASec-dependent conversion of O-phosphoserine (Sep) to Sec. In this two-step pathway, O-phosphoseryl-tRNASec kinase (PSTK) converts Ser-tRNASec to SeptRNASec. This misacylated tRNA is the obligatory precursor for a Sep-tRNA:Sec-tRNA synthase (SepSecS); this protein was previously annotated as SLA/LP. The human and archaeal SepSecS genes complement in vivo an Escherichia coli Sec synthase (SelA) deletion strain. Furthermore, purified recombinant SepSecS converts SeptRNASec into Sec-tRNASec in vitro in the presence of sodiumselenite and purified recombinant E. coli selenophosphate synthetase (SelD). Phylogenetic arguments suggest that Sec decoding was present in the last universal common ancestor. SepSecS and PSTK coevolved with the archaeal and eukaryotic lineages, but the history of PSTK is marked by several horizontal gene transfer events, including transfer to non-Sec-decoding Cyanobacteria and fungi.

  • murine Liver Antigen presenting cells control suppressor activity of cd4 cd25 regulatory t cells
    Hepatology, 2005
    Co-Authors: C Wiegard, Johannes Herkel, Christian Frenzel, Karljosef Kallen, Edgar Schmitt, Ansgar W. Lohse
    Abstract:

    CD4(+)CD25(+) regulatory T cells (Treg) are important mediators of peripheral immune tolerance; however, whether Treg participate also in hepatic immune tolerance is not clear. Therefore, we tested the potential of Treg to suppress stimulation of CD4(+) T cells by Liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC), or hepatocytes. In the absence of Treg, all 3 types of Liver cells could stimulate CD4(+) T cell proliferation; in the presence of Treg, however, CD4(+) T cell proliferation was suppressed. Interaction with KC even stimulated the expansion of the Treg population; LSEC or hepatocytes, in contrast, could not induce proliferation of Treg. Because Liver inflammation can be induced by infection, we tested the potential of Liver cells to modify Treg suppressor activity in the presence of microbial signals. In the presence of immune-stimulatory CpG-oligonucleotides, LSEC, KC, and hepatocytes could indeed overcome Treg-mediated suppression; in the presence of lipopolysaccharide (LPS), however, only KC and hepatocytes, but not LSEC, could overcome Treg suppressor activity. Hepatocytes from mice with deficient toll-like receptor-4 signaling failed to abrogate Treg suppression in response to LPS, indicating that overcoming Treg suppressor activity was indeed a response of the Liver cell and not of the Treg. In conclusion, Treg can suppress CD4(+) T cell stimulation by Liver cells. However, in response to microbial signals, the Liver cells can overcome the suppressive activity of Treg. Thus, Liver cells may facilitate the transition from hepatic immune tolerance to hepatic inflammation by controlling Treg suppressor activity.

  • antibodies to soluble Liver Antigen Liver pancreas and hla risk factors for type 1 autoimmune hepatitis
    The American Journal of Gastroenterology, 2002
    Co-Authors: Albert J. Czaja, Peter T. Donaldson, Ansgar W. Lohse
    Abstract:

    Antibodies to soluble Liver Antigen/Liver pancreas and HLA risk factors for type 1 autoimmune hepatitis

Albert J. Czaja - One of the best experts on this subject based on the ideXlab platform.

  • Management of Recalcitrant Autoimmune Hepatitis
    Current Hepatitis Reports, 2013
    Co-Authors: Albert J. Czaja
    Abstract:

    Recalcitrant autoimmune hepatitis occurs in 7 % of patients treated with conventional corticosteroid regimens. High dose prednisone alone or a lower dose combined with azathioprine is the first line treatment. Doses are reduced after each month of improvement until clinical stability is achieved. Laboratory tests improve in 75 %, but histological resolution eventuates in only 20 %. Second line therapy with calcineurin inhibitors can be instituted for non-response or treatment intolerance, and mycophenolate mofetil is another option. Composite experiences indicate that 93-98 % of patients treated with cyclosporine or tacrolimus improve, whereas mycophenolate mofetil is effective in only 10 % with recalcitrant disease. Rituximab, rapamycin, non-mitogenic monoclonal antibodies to CD3, abatacept, and mesenchymal stem cell transplantation are plausible but untested rescue treatments. Problematic patients can be identified early by clinical phenotype, mathematical models, antibodies to soluble Liver Antigen, and rapidity of response to conventional corticosteroid treatment. Salvage therapies must not delay or supersede Liver transplantation.

  • Advances in the Current Treatment of Autoimmune Hepatitis
    Digestive Diseases and Sciences, 2012
    Co-Authors: Albert J. Czaja
    Abstract:

    Current treatment strategies for autoimmune hepatitis are complicated by frequent relapse after drug withdrawal, medication intolerance, and refractory disease. The objective of this review is to describe advances that have improved treatment outcomes by defining the optimum objectives of initial therapy, managing relapse more effectively, identifying problematic patients early, and incorporating the new pharmacological interventions that have emerged as frontline and salvage therapies. Initial corticosteroid treatment should be continued until serum aminotransferase, γ-globulin, and immunoglobulin G levels are normal, and maintenance of this improvement for 3–8 months before Liver tissue assessment. Improvement to normal Liver tissue is the ideal histological result that justifies drug withdrawal, but it is achievable in only 22 % of patients. Minimum portal hepatitis, inactive cirrhosis, or minimally active cirrhosis is the most common treatment end point. Relapse after drug withdrawal warrants institution of a long-term maintenance regimen, preferably with azathioprine. Mathematical models can identify problematic adult patients early, as also can clinical phenotype (age ≤30 years and HLA DRB1*03), rapidity of treatment response (≤24 months), presence of antibodies to soluble Liver Antigen, and non-white ethnicity. The calcineurin inhibitors (cyclosporine and tacrolimus) can be effective in steroid-refractory disease; mycophenolate mofetil can be corticosteroid-sparing and effective for azathioprine intolerance; budesonide combined with azathioprine can be effective for treatment-naïve, non-cirrhotic patients. Standard treatment regimens for autoimmune hepatitis can be upgraded without adjustments that require major new expertise.

  • Prognostic implications of antibodies to Ro/SSA and soluble Liver Antigen in type 1 autoimmune hepatitis
    Liver international : official journal of the International Association for the Study of the Liver, 2011
    Co-Authors: Aldo J. Montano-loza, Zakera Shums, Gary L. Norman, Albert J. Czaja
    Abstract:

    Background: Antibodies to soluble Liver Antigen are frequently co-expressed with antibodies to ribonucleoprotein/Sjogren's syndrome A (Ro/SSA) in autoimmune hepatitis. Aims: Our goals were to evaluate the prognostic implications of antibodies to Ro/SSA in type 1 autoimmune hepatitis and to determine their independence from antibodies to soluble Liver Antigen. Methods: Three hundred and seventy-six serum samples from 170 patients were tested by enzyme immunoassays. Results: Sixty-five patients (38%) had antibodies to Ro52; 11 patients (6%) had antibodies to Ro60; and 27 patients had antibodies to soluble Liver Antigen (16%). Twenty-six patients with antibodies to Ro52 had antibodies to soluble Liver Antigen (40%), and 26 patients with antibodies to soluble Liver Antigen had antibodies to Ro52 (96%). Patients with antibodies to Ro52 and antibodies to soluble Liver Antigen had a higher frequency of human leucocyte Antigen (HLA) DRB1*03 (78 vs 50%, P=0.05) and lower occurrence of HLA DRB1*04 (22 vs 57%, P=0.01) than patients with antibodies to Ro52 alone. Antibodies to Ro52 alone [hazard ratio (HR), 2.90; 95% confidence interval (CI), 1.18–7.14, P=0.02] and antibodies to Ro52 in conjunction with antibodies to soluble Liver Antigen (HR, 2.98; 95% CI, 1.07–8.43, P=0.04) were independently associated with the development of cirrhosis and hepatic death or Liver transplantation. Conclusions: Antibodies to Ro52 alone and antibodies to Ro52 in conjunction with antibodies to soluble Liver Antigen are independently associated with a poor prognosis in type 1 autoimmune hepatitis. The prognostic implications ascribed to antibodies to soluble Liver Antigen may reflect their almost invariable concurrence with antibodies to Ro52.

  • Autoantibodies as Prognostic Markers in Autoimmune Liver Disease
    Digestive Diseases and Sciences, 2010
    Co-Authors: Albert J. Czaja
    Abstract:

    Certain autoantibodies in autoimmune Liver disease have prognostic implications that are under-utilized and under-developed. The goals of this review are to indicate progress in characterizing the autoantibodies with prognostic connotations and to indicate the feasibility and importance of discovering other markers. Prime source and review articles in English were selected by a Medline search through 2010. Antibodies to soluble Liver Antigen, actin, Liver cytosol type 1, asialoglycoprotein receptor, chromatin, cyclic citrullinated peptide, and uridine glucuronosyltransferases have been associated with the occurrence, severity, and progression of autoimmune hepatitis, and antibodies to Sp100, gp210, and centromere have had similar implications in primary biliary cirrhosis. Antibodies to soluble Liver Antigen have shown the most promise in autoimmune hepatitis as they have been associated with severe histological changes, long durations of treatment, relapse after drug withdrawal, and high frequency of Liver failure. Antibodies to the nuclear rim pore protein, gp210, have shown the most promise in primary biliary cirrhosis as they have been associated with severe interface hepatitis, lobular inflammation, and progression to Liver failure. The major limitations of the autoantibodies have been their lack of standardized assays, low negative predictabilities, and fluctuating levels. Performance parameters will improve as critical pathogenic pathways, comprehensive testing batteries, and standardized assays through international exchange workshops are developed. Progress has been made in identifying the serological markers of prognosis in autoimmune Liver disease, and they promise to reflect critical disease mechanisms and enhance patient management.

  • Nonstandard antibodies as prognostic markers in autoimmune hepatitis.
    Autoimmunity, 2004
    Co-Authors: Albert J. Czaja, Zakera Shums, Gary L. Norman
    Abstract:

    Background: Antibodies to actin, chromatin, soluble Liver Antigen/Liver pancreas and Liver cytosol type 1 have been ascribed prognostic value in autoimmune hepatitis. Aim: Evaluate the performance parameters of these nonstandard autoantibodies and determine the critical battery for clinical application.Methods: All antibodies were tested concurrently by enzyme immunoassay in 106 patients who had reached a treatment outcome. Tests were repeated in 149 serum samples obtained later to assess durability of the findings.Results: Antibodies to chromatin and soluble Liver Antigen/Liver pancreas were superior to the other markers in predicting relapse. Patients with antibodies to chromatin and/or soluble Liver Antigen/Liver pancreas relapsed more frequently than patients without these markers (100 versus 79%, p

Fernando Alvarez - One of the best experts on this subject based on the ideXlab platform.

  • Mouse Liver-specific CD8(+) T-cells encounter their cognate Antigen and acquire capacity to destroy target hepatocytes.
    Journal of autoimmunity, 2012
    Co-Authors: Sylvie Chabot, Kathie Béland, Fernando Alvarez, Amin Fakhfakh, Alain Lamarre, Michael B. A. Oldstone, Idriss Djilali-saiah
    Abstract:

    CD8+ T-cell immune response to Liver Antigens is often functionally diminished or absent. This may occur via deletion of these autoaggressive T-cells, through the acquisition of an anergic phenotype, or via active suppression mediated by other cell populations. We generated a double transgenic model in which mice express CD8+ T-cells specific for the lymphocytic choriomeningitis virus nucleoprotein (LCMV-NP) and LCMV-NP as a hepatic neo-autoAntigen, to study the immunological response of potentially Liver Antigen autoaggressive CD8+ T-cells. Autoreactive transgenic CD8+ T-cells were analyzed for functionality and cytotoxic effector status. Despite severe peripheral deletion of Liver-specific CD8+ T-cells, a fraction of autoreactive NP-specific CD8+ T-cells accumulate in Liver, resulting in hepatocyte injury and production of auto-antibodies in both male and female mice. NP-specific intrahepatic T-cells showed capacity to proliferate, produce cytokines and up-regulate activation markers. These data provide in vivo evidence that autoreactive CD8+ T-cells are activated in the Liver and developed an inflammatory process, but require additional factors to cause severe autoimmune destruction of hepatocytes. Our new model will provide a valuable tool for further exploration of the immunological response involved in inflammatory Liver diseases, including autoimmune hepatitis.

  • Anti-soluble Liver Antigen (SLA) antibodies in chronic HCV infection.
    Autoimmunity, 2004
    Co-Authors: Susana Vitozzi, Pascal Lapierre, Idriss Djilali-saiah, Gabriel Marceau, Kathie Béland, Fernando Alvarez
    Abstract:

    Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble Liver Antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-Liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA Antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble Liver Antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the Antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the Liver injury of patients chronically infected by HCV needs further investigation.

  • Anti-soluble Liver Antigen/Liver-pancreas (SLA/LP) antibodies in pediatric patients with autoimmune hepatitis.
    Autoimmunity, 2002
    Co-Authors: Susana Vitozzi, Pascal Lapierre, Idriss Djilali-saiah, Fernando Alvarez
    Abstract:

    Antibodies against soluble Liver Antigen/Liver-pancreas (SLA/LP) have been associated with severe autoimmune hepatitis (AIH) and poor outcome, but most of these reports have focused on adult patients. The aim of this study was to assess the prevalence and clinical significance of anti-SLA/LP antibodies in a pediatric population with AIH. We developed a quantitative enzyme-linked immunoassay (ELISA), a Western blot (WB) and an immunoprecipitation assay (IPA) based on recombinant cDNA from activated Jurkat cells. The specificity of these tests was validated by testing 200 serum samples from healthy subjects, and from patients with Liver and non-Liver diseases. Anti-SLA/LP antibodies were found in patients with type 1 and type 2 AIH. The prevalence of these antibodies in patients with type 1 AIH was: 42% when tested by ELISA, 15% by WB and 50% by IPA. In patients with type 2 AIH, the prevalence rates were 42% by ELISA, 18% by WB and 44% by IPA. The mean titer values for anti-SLA/LP antibodies was significantly higher in type 2 AIH (1:1,300 +/- 339) than in type 1 AIH (1:600 +/- 71; p < 0.0001) and closely associated with higher titers of anti-Liver kidney microsome type 1 (LKM1) and anti-Liver cytosol type 1 (LC1) antibodies in sera. The presence of anti-SLA/LP showed a significant female preponderance in type 1 and 2 AIH patients (p = 0.0003 and p = 0.003, respectively), and was significantly correlated with a lower age at diagnosis (p = 0.05) in type 1 AIH patients. In conclusion, anti-SLA/LP antibodies in pediatric patients are associated with both type 1 and 2 AIH.

Gary L. Norman - One of the best experts on this subject based on the ideXlab platform.

  • Prognostic implications of antibodies to Ro/SSA and soluble Liver Antigen in type 1 autoimmune hepatitis
    Liver international : official journal of the International Association for the Study of the Liver, 2011
    Co-Authors: Aldo J. Montano-loza, Zakera Shums, Gary L. Norman, Albert J. Czaja
    Abstract:

    Background: Antibodies to soluble Liver Antigen are frequently co-expressed with antibodies to ribonucleoprotein/Sjogren's syndrome A (Ro/SSA) in autoimmune hepatitis. Aims: Our goals were to evaluate the prognostic implications of antibodies to Ro/SSA in type 1 autoimmune hepatitis and to determine their independence from antibodies to soluble Liver Antigen. Methods: Three hundred and seventy-six serum samples from 170 patients were tested by enzyme immunoassays. Results: Sixty-five patients (38%) had antibodies to Ro52; 11 patients (6%) had antibodies to Ro60; and 27 patients had antibodies to soluble Liver Antigen (16%). Twenty-six patients with antibodies to Ro52 had antibodies to soluble Liver Antigen (40%), and 26 patients with antibodies to soluble Liver Antigen had antibodies to Ro52 (96%). Patients with antibodies to Ro52 and antibodies to soluble Liver Antigen had a higher frequency of human leucocyte Antigen (HLA) DRB1*03 (78 vs 50%, P=0.05) and lower occurrence of HLA DRB1*04 (22 vs 57%, P=0.01) than patients with antibodies to Ro52 alone. Antibodies to Ro52 alone [hazard ratio (HR), 2.90; 95% confidence interval (CI), 1.18–7.14, P=0.02] and antibodies to Ro52 in conjunction with antibodies to soluble Liver Antigen (HR, 2.98; 95% CI, 1.07–8.43, P=0.04) were independently associated with the development of cirrhosis and hepatic death or Liver transplantation. Conclusions: Antibodies to Ro52 alone and antibodies to Ro52 in conjunction with antibodies to soluble Liver Antigen are independently associated with a poor prognosis in type 1 autoimmune hepatitis. The prognostic implications ascribed to antibodies to soluble Liver Antigen may reflect their almost invariable concurrence with antibodies to Ro52.

  • Nonstandard antibodies as prognostic markers in autoimmune hepatitis.
    Autoimmunity, 2004
    Co-Authors: Albert J. Czaja, Zakera Shums, Gary L. Norman
    Abstract:

    Background: Antibodies to actin, chromatin, soluble Liver Antigen/Liver pancreas and Liver cytosol type 1 have been ascribed prognostic value in autoimmune hepatitis. Aim: Evaluate the performance parameters of these nonstandard autoantibodies and determine the critical battery for clinical application.Methods: All antibodies were tested concurrently by enzyme immunoassay in 106 patients who had reached a treatment outcome. Tests were repeated in 149 serum samples obtained later to assess durability of the findings.Results: Antibodies to chromatin and soluble Liver Antigen/Liver pancreas were superior to the other markers in predicting relapse. Patients with antibodies to chromatin and/or soluble Liver Antigen/Liver pancreas relapsed more frequently than patients without these markers (100 versus 79%, p

  • Frequency and significance of antibodies to soluble Liver Antigen/Liver pancreas in variant autoimmune hepatitis.
    Autoimmunity, 2002
    Co-Authors: Albert J. Czaja, Zakera Shums, Gary L. Norman
    Abstract:

    Background: Antibodies to soluble Liver Antigen/Liver pancreas are highly specific markers of autoimmune hepatitis. Aims: Determine the frequency and clinical significance of these antibodies in the variant syndromes. Methods: Antibodies to soluble Liver Antigen/Liver pancreas were determined in 28 patients with variant forms, including 10 with cryptogenic chronic hepatitis and 18 with cholestatic variants. One hundred and seventy-two patients with classical autoimmune hepatitis were similarly tested. Results: Seven of the 28 patients with variant forms had the antibodies, and this frequency was not statistically different than that in classical disease (25 vs. 12%, p = 0.08). Antibodies were most common in patients with cryptogenic chronic hepatitis (40%). Seropositive patients were indistinguishable from seronegative patients with variant forms, and they responded as well to corticosteroid therapy as patients with autoimmune hepatitis. Relapse after corticosteroid withdrawal invariably occurred in the s...

  • Soluble Liver Antigen (SLA) antibody detection by ELISA and multiplexing technologies
    Clinical and Applied Immunology Reviews, 2002
    Co-Authors: Zakera Gandhi, Angsar Lohse, Johannes Herkel, Gary L. Norman
    Abstract:

    Abstract Objective: Develop and evaluate assays for the detection of antibodies to soluble Liver Antigen (SLA). SLA, also known as Liver/pancreas antibody, was found to be 100% specific for autoimmune hepatitis (AIH) in a recent study of 2000 sera collected from individuals with various disease conditions and healthy individuals (Wies et al., Lancet 2000; 355:1510). Although SLA antibodies occur in only about 30% of patients with autoimmune hepatitis, they are found in some individuals with AIH who are negative for other autoantibodies. Methods: Specimens from patients with autoimmune hepatitis, non-autoimmune Liver disease, various autoimmune conditions, as well as specimens from healthy individuals were tested by the INOVA QUANTA Lite™ SLA (Soluble Liver Antigen) ELISA. The ELISA test uses a recombinant SLA Antigen. The feasibility of simultaneous detection of antibodies to SLA, LKM-1, and M-2 antibodies was also determined using the QuantaPlex™ test system (Luminex). Results: Site 1 (San Diego): Testing of 132 specimens from normal, healthy individuals with ages ranging from 5 to 69 years old, resulted in a specificity of 100% (132/132). A second panel, consisting of 10 clinically-defined samples obtained from Dr. Lohse (5 positive and 5 negative), was tested and in complete agreement with the results obtained in the Mainz laboratory by an inhibition ELISA assay and western blot analysis. A panel of 18 specimens positive for various autoimmune or disease antibodies, including GBM, LKM-1, ANA, SLE, M-2 and GPA, were all found to be negative on the SLA ELISA. The multiplex assay was able to clearly discriminate and identify SLA, LKM-1, and M-2 positive samples and offers a promising new methodology for evaluation of patients with suspected Liver disease. Site 2 (Mainz): A panel of 200 sera were tested. These included 32 SLA/LP positive AIH sera, 18 SLA/LP negative AIH sera, 100 sera from viral hepatitis patients, 15 sera from patients with non-AIH Liver diseases and sera from 35 patients with various disease conditions. 31 of the 32 SLA positive sera were clearly positive and one was equivocal. Excluding the equivocal result, the sensitivity was 100%. Conclusions: Our data show that with the exclusion of the 1 equivocal result, the SLA ELISA test had 100% specificity and 100% sensitivity. No cross-reactivity was seen with sera positive for other autoimmune makers. Availability of assays for detection of SLA antibodies will provide a new marker to assist in the diagnosis of patients with autoimmune hepatitis. Detection of SLA antibodies is especially valuable for testing the 10–15% of AIH patients who are negative for conventional autoantibodies.

Peter T. Donaldson - One of the best experts on this subject based on the ideXlab platform.