Disease relevance of SEPSECS

• Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis [1].
• Methods We tested 2000 serum samples from patients with various liver diseases and controls for SLA autoantibodies by inhibition ELISA [1].
• Expressed in Escherichia coli, SLA-p35 showed dose-dependent and complete blocking of reactivity to native SLA antigen after preabsorption with the 35-kd recombinant protein [2].
• Autoantibodies against a soluble liver antigen (SLA) were detected in 23 patients with HBsAg-negative chronic active hepatitis (CAH) but not in 502 patients with various other hepatic and non-hepatic disorders or 165 healthy blood donors [3].
• All individuals presented with the cutaneous clinical form of leishmaniasis and were analyzed for proliferative responses to LACK antigen and SLA, frequency of lymphocyte subpopulations (analyzed ex vivo), and antigen-induced (LACK and SLA) cytokine production at the single-cell level (determined by flow cytometry) [4].

High impact information on SEPSECS

• Autoantibodies to soluble liver antigen (SLA) and to liver and pancreas antigen (LP) have been described as disease specific, occurring in about 30% of all patients with autoimmune hepatitis, but no standardised assays are available [1].
• Identified clones were tested against a panel of serum samples positive for SLA and LP autoantibodies and control serum samples, and the epitope mapped by deletion mutants and exonuclease digestion [1].
• CONCLUSIONS: Glutathione S-transferase subunit proteins represent the major autoantigen in anti-SLA-positive AIH [5].
• The insertion of the putative retrotransposon was shown to interfere with gene expression, with no SLA transcripts being detected by RNA gel blot analysis in a self-incompatible B. oleracea var botrytis line carrying an interrupted SLA gene [6].
• However, analysis of seven B. oleracea var botrytis lines exhibiting both self-compatible and self-incompatible phenotypes showed that these lines carry an S allele very similar or identical to that of the B. oleracea var acephala line and that the SLA gene is interrupted by an insert in all seven lines [6].

Chemical compound and disease context of SEPSECS

• We previously described autoantibodies against a UGA serine tRNA-protein complex (tRNP(Ser)Sec) in patients with type-1 autoimmune hepatitis [1] and now define the specificity and frequency of this autoantibody and the DNA sequence encoding the tRNA(Ser)Sec-associated antigenic protein [7].
• Autoimmune hepatitis is subdivided into two major types: AIH type 1 is characterized by the detection of ANA, SMA, ANCA, anti-ASGP-R, and anti-SLA/LP [8].
• 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 [9].
• OBJECTIVE: To investigate the effects of the peroxidase system (LP, H2O2, SCN) and its components on the activity of glucosyltransferase D (GtfD) originating from Streptococcus mutans (S. mutans) [10].

Biological context of SEPSECS

• We have performed immunoscreening of a human liver gene expression library with an anti-SLA-positive serum [2].
• This study aims to map the exact epitope(s) recognized by SLA/LP autoantibodies and to assess the role of molecular mimicry between microbial antigens and self-epitopes [11].
• Recent cloning data relating to the target antigen(s) of autoantibodies in autoimmune hepatitis patients that react with a soluble liver antigen (SLA) and a liver-pancreas antigen (LP) have revealed that these two autoantibodies are identical and that the cloned antigen shows 99% amino acid sequence homology with tRNP(Ser)Sec [7].
• Recognition of xeno-(HLA, SLA) major histocompatibility complex antigens by mouse cytotoxic T cells is not H-2 restricted: a study with transgenic mice [12].
• The number of functional SLA classical class I genes, as defined by serology, probably varies from one to four, depending on the haplotype [13].

Anatomical context of SEPSECS

• Thus 19 patients had antibodies to nuclei and 96 to actin but none to liver-kidney microsomes, hereby suggesting that antibody to liver-pancreas antigen may define another subgroup of autoimmune hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)[14]
• These data and absorption studies with cell organelles indicate that liver-pancreas antigen is a cytosolic protein [14].
• In swine, the major histocompatibility complex (Mhc) or swine leukocyte antigen (SLA) is located on chromosome 7 and divided by the centromere [13].
• Human peripheral blood CD4+ lymphocytes showed strong proliferation in response to NPICs, likely because of occasional swine leukocyte antigen (SLA) class II+ cells in the NPIC preparations [15].
• Membranes were labeled with SLA or SLC, and the analogs in the outer leaflet were selectively reduced at 4C using 6-O-phenylascorbic acid [16].

Associations of SEPSECS with chemical compounds

• Therefore we used a new theoretical method called fold recognition and could show that the SLA/LP sequence is compatible with the architecture of the superfamily of pyridoxal phosphate (PLP; vitamin B6)-dependent transferases [17].
• PBSCs mobilized with pSCF/pIL-3 were infused into an SLA-matched recipient conditioned with cyclophosphamide (50 mg/kg) and total body irradiation 1150 cGy [18].
• To study the biological implications of this modification, CaCo-2 cells were incubated with either LA or sulphated lithocholic acid (3-sulpholithocholic acid, SLA), and in some experiments with taurine-conjugated lithocholic acid [19].
• Patients treated with gemcitabine had a similar 10-month LP rate (62% vs. 61%), 10-month DM rate (55% vs. 47%), 1-year OS rate (42% vs. 28%), and median OS duration (11 months vs. 9 months) to patients treated with 5 FU (all p = NS) [20].
• Altrenogest (ALT), a synthetic progestogen, and exogenous gonadotropins were administered to the Swine Leukocyte Antigen (SLA) inbred miniature pig that typically has a reduced ovulation rate and small litter size [21].

Other interactions of SEPSECS

• In conclusion, the exquisite epitope specificity and IgG subtype are evidence for the maturity of the SLA/LP autoantibody response; a specific autoantigen-driven process underlying the immunopathogenesis is likely [11].

Analytical, diagnostic and therapeutic context of SEPSECS

• Autoantibodies to soluble liver antigen and liver pancreas (SLA/LP) have been described as specific markers for Autoimmune Hepatitis (AIH), occurring in about 20% of patients with AIH [11].
• Anti-SLA cannot be detected by immunofluorescence [3].
• The immunoprecipitation of the SLA RNA by antibodies against common proteins does not require an association between the SLA RNA and the SL RNP [22].
• The SLA antigens were reduced and alkylated, and the component heavy and light chains were isolated by gel filtration under dissociating conditions [23].
• CONCLUSIONS: Antibodies to SLA/LP can be reliably detected by these standardised immunoassays based on recombinant antigen [24].

References