SUBSTITUTION OF ENZYME DEFECTS OF THE LIVER: SYNGENEIC TRANS- PLANTATION OF HEPATIC TISSUE INTO SPLEEN IN A RAT MODEL

H. L6sqen, T. Yamamoto, G. Brunner Division of Clin. Pharmacology, Univ. G6ttingen, FRG

Transplantation (Tx) o£ normal hepatic tissue into the spleen o£ an organism with a hepatic enzyme defect theoretically might be an effective form of enzyme substitution. To test this hypothesis we have studied in the rat the morphology and several enzyme activities of the proliferated hepatic tissue after syngeneie Tx into the spleen of 5xI06 isolated adult hepatocy- tes (H) and, for comparison, o£ 200 mg fetal liver tissue (FLT). Eighteen months after Tx of H up to 45% o£ the spleen was occupied by hepatic tissue showing morphological structures nearly comparable to those o£ a normal liver. Histochemical analysis revealed glycogen granules, G-6 phosphatase and intraeellular albumin. In this hepatic tissue activities of ALT(cytosol), GIIPDH (cytosol),and NADPH-cytochrom e reduetase (microsomes) were reduced to 15-30% of normal liver. Activities o£ AST (homogenate) were comparable to controls , and of GIDH (homogenate) increased to 190%. A portacaval shunt increased activities 3-5 fold (n=2). Tx of FLT led to a 35% hepatization of the spleen already after three months. Histologically about 50% of the hepatic tissue was composed o£ proliferated bile ducts. In contrast to H-Tx, all enzyme activities of proliferated FLT were reduced to <5% of normal liver. It is concluded that Tx o£ FLT results in a much faster proliferation of the transplant but without production of useful amounts of enzymes. Tx of H, however, has the potential to supply liver function to an extent of approxi- mately 5% of a normal liver. This might be sufficient for substitution of some enzyme defects in man.

DIFFERENT SUBCLASS DISTRIBUTION FOR SUBTYPES OF ANTIHITOCHO.~DRIAL AND LIVER KIDNEY i, IICROSOt4AL ANTIBODIES IN AUTOIr, I~.IUNE LIVER DISEASES

M. Manns, G. Gerken, A. Kyriatsoulis, M.Staritz, K.H. I'leyer zum BUschen---felde I. Department of Internal Medicine, University of

14ainz, FRG.

Antimitochondrial antibodies (AMA) are associated with primary biliary cirrhosis (PBC); different PBC specific subtypes have been described (J Hepatol 1, Suppl. 2, 279, 1985). Liver kidney microsomal antibodies (LKM) are markers for a subgroup of autoimmune type chronic active hepatitis (CAH-AI). All these autoantibodies are predominantly IgG. Heavy chain isotype expression of immunoglobulins is thought to be regulated by both antigen and regulatory T-cells. Therefore we evaluated the distribution of the autoantibcdies within the IgG subclasses. We analysed sera from 20 patients (pt) with PBC, all positive for AMA by indirect immunofluorescence (IF); 10 sera were positive for subtype anti p62, I 0 for subtype anti p48. Furthermore I 0 LKM positive and for control 5 antinuclear antibody (ANA) positive sera from patients with SLE were included. IgG subclasses of autoant~es were determined by IF on rat kidney (AMA) and liver (LKM, ANA) tissue sections using subclass specific mouse monoclonal antibodies: NL 1 6 (anti IgG1 ), GOM-2 (anti IgG2), ZG-4 (anti IgG3), RJ-4 (anti IgG4). Results were expressed as end point titers. PBC sera with subtypes anti p62 were all positive for subclass IgG1 and IgG3, 6/10 for IgG2 and 1/10 for IgG4. All 10 sera with AMA subtype anti p48 were positive for IgG1, 5/10 for IgG2, 3/10 for IgG3 and 2/10 for IgG4. LKM antibodies were all positive for subclass IgG1, 1/10 for IgG2, 0/10 for IgG3 but 7/10 for IgG4. All 5 sera from SLE were positive for ANA in all subclasses. - Incidence and titers of subclass specific autoantilxxlies did not correlate with total subclass concentrations. The different IgG subclass distribution of these autoantibcdies may be regarded as evidence for different specific defects in immunoregulation in subgroups of PBC and CAH-AI.

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