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. 1998 May;42(5):721–726. doi: 10.1136/gut.42.5.721

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

L Muratori 1, M Cataleta 1, P Muratori 1, M Lenzi 1, F Bianchi 1
PMCID: PMC1727121  PMID: 9659171

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. 



Keywords: autoantibodies; immunoblotting; LKM1; LC1; immunosuppression

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Figure 2 .

Figure 2

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(A) Representative behaviour of liver cytosol antibody type 1 (LC1) concentration and serum alanine aminotransferase (ALT) levels during immunosuppression in patient 19. LC1 immunoreactivity against the 58 kDa (kD) human liver cytosolic (HLC) polypeptide was evaluated by immunoblotting visualised by enhanced chemiluminescence and quantified by densitometric analysis. A clear correlation was observed between LC1 concentration and ALT levels. (B) Independent behaviour of LC1 with respect to liver/kidney microsomal antibody type 1 (LKM1) in patient 13. LKM1 reactivity against the 50 kDa human liver microsomal (HLM) protein—that is, CYP2D6—remained essentially unchanged. An additional 52 kDa band, corresponding to residual human IgG both in microsomal and cytosolic fractions, is also evident. 


Figure 1 .

Figure 1

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Liver cytosol antibody type 1 (LC1) (A) and liver/kidney microsomal antibody type 1 (LKM1) (B) concentrations were evaluated at onset and during treatment induced remission in patients with type 2 autoimmune hepatitis. LC1, but not LKM1, was decreased significantly by immunosuppressive therapy during which biochemical and immunological parameters were normalised (F test = 87.84 p = 0.0001; factorial analysis of variance). 


Figure 3 .

Figure 3

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Liver cytosol antibody type 1 (LC1) (A; patient 12) and liver/kidney microsomal antibody type 1 (LKM1) (B; patient 9) concentrations were sequentially reported in parallel with serum alanine aminotransferase (ALT) levels. ALT flares occurred during immunosuppression withdrawal. LC1 concentration reflects ALT levels at onset, during the first remission, during hepatic flares, and again during the subsequent remission. LKM1 concentration, on the other hand, was consistently elevated throughout follow up, independent of biochemical remission or ALT flares. 


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