Liver/kidney microsomal antibody type 1 and liver cytosol antibody type 1 concentrations in type 2 autoimmune hepatitis

Abstract

Background-Liver/kidney microsomal antibody type 1 (LKM1) and liver cytosol antibody type 1 (LC1) are the serological markers of type 2 autoimmune hepatitis (AIH). Aims-Since LKM1 and LC1 react against two distinct liver specific autoantigens (cytochrome P450IID6 (CYP2D6) and a 58 kDa cytosolic polypeptide respectively), the aim was to see whether LKM1 and LC1 concentrations correlate with liver disease activity. Patients-Twenty one patients with type 2 AIH were studied.Methods-All sera were tested by indirect immunofluorescence, counterimmunoelectrophoresis, and immunoblotting visualised by enhanced chemiluminescence. To evaluate LKM1 and LC1 levels, the 50 kDa microsomal reactivity (corresponding to CYP2D6) and the 58 kDa cytosolic reactivity were quantified by densitometric analysis. Results-Seven patients were positive for LKM1, nine for LC1, and five for both. Serial serum samples at onset and during immunosuppressive treatment were analysed in 13 patients (four positive for LKM1, six positive for LC1 and three positive for both). During remission, LKM1 concentration remained essentially unchanged in six of seven patients, and decreased in only one. Conversely, in two of nine patients, LC1 was completely lost, and, in the remaining seven, LC1 concentration was reduced by more than 50%. After immunosuppression tapering or withdrawal, flare ups of liver necrosis ensued with increasing LC1 concentration, but not LKM1. Conclusions-LC1 concentration, at variance with that of LKM1, parallels liver disease activity, and its participation in the pathogenic mechanisms of liver injury can be hypothesised. (Gut 1998;42:721-726)

Forkhead box p3+ regulatory T cell underlies male resistance to experimental type 2 autoimmune hepatitis

“…Interestingly, anti-LC1 autoantibody titers were found to parallel disease activity in type 2 AIH patients. 19 These observations suggest that a loss of B cell tolerance against hepatic autoantigens could be an initial and fundamental step in the development of late-onset liver autoimmunity.…”

Distinct epitopes on formiminotransferase cyclodeaminase induce autoimmune liver cytosol antibody type 1

“…The latter is suggested by the finding that global levels of circulating LC1 seem to parallel, at least biochemically, the occurrence of liver damage in LC1-positive patients with autoimmune hepatitis. 6 It is likely that there is a relationship between the B-cell (and possibly T-cell) epitope spreading process and the exacerbations and remissions of autoimmune liver disease. FIG.…”

“…1,2 In addition, serum LC1 concentrations appear to fluctuate in parallel with aminotransferase levels, an observation that suggests a possible role of LC1 autoreactivity in the pathogenic mechanisms leading to hepatocyte injury. 6 In a recent report, Lapierre et al after screening a complementary DNA (cDNA) library of HepG2 cells with an LC1-positive serum isolated a clone with high sequence homology to pig formiminotransferase cyclodeaminase (FTCD), and showed that a construct encoding the C-terminal portion of FTCD can be recognized by LC1 antibodies. 7 FTCD is a mammalian metabolic enzyme involved in the conversion of histidine to glutamic acid, 8 and is most highly expressed in the liver.…”

Autoimmune liver serology: Current diagnostic and clinical challenges

“…Anti-SLA antibodies denote patients with a more severe course of AIH and a propensity for relapse after corticosteroid withdrawal compared to their negative counterparts [49,81,121,122] . AIH-2 patients with anti-LC1 antibodies have histologically more severe disease compared to those without anti-LC1 antibodies [35,123,124] . PBC AMA titres do not seem to be associated with disease severity but those of the IgG3 subclass may identify patients prone to develop more severe disease compared to those without AMA-IgG3 [116,125] .…”