Antibodies liver-kidney microsome

Czaja, A.J., Manns, M.P., Homburger, H.A. Frequency and significance of antibodies to liver/kidney microsome Type 1 in adults with chronic active hepatitis. Gastroenterology 1992 103 1290-1295... 

In 25 children with chronic hepatitis C, pretreatment positivity for liver/kidney microsomal type 1 (LKM-1) antibodies was associated with more frequent treatment-limiting increases in serum alanine transaminase activity (256). Withdrawal of interferon alfa-2b because of hypertransaminasemia was required in three of four LKM-1 positive children compared with two of the 21 LKM-1 negative children. Although none developed features of autoimmune hepatitis, careful surveillance of hepatic function is recommended in LKM-l-positive patients. 

Collectively, several antibodies (mostly antinuclear, antithyroid, parietal cell, liver/kidney microsome, and smooth muscle antibodies, and rheumatoid factor) can be detected before interferon alfa treatment in about one-third of patients. Increased titers or the occurrence of various autoantibodies were observed in 4-30% of previously autoantibody-negative patients (21,156). These autoantibodies do not affect the response to... 

Porta G, Gayotto L, Alvarez F. Anti-liver-kidney microsome antibody-positive autoimmune hepatitis presenting as fulminant liver failure. J Pediatr Gastroenterol Nutr 1990 11 138-40. 

Homberg, J.C. Andre, C. Abuaf, N. A New and Anti-liver Kidney Microsome Antibody in Tienilic Acid Induced Hepatitis, Clin. Exp. Immunol. 55, 561-570 (1984). 

Autoimmune hepatitis (AIH). Chronic autoimmune-mediated hepatic inflammation characterized by antinuclear (ANA), smooth muscle (SMA)/anti-F-actin, liver-kidney microsomal (LKM), and soluble liver antigen (SLA) antibodies. Autoimmune hepatitis constitutes 10-20% of all cases of chronic hepatitis, ft may be idiopathic (Alff type 1, 2, and 3), part of autoimmune polyendocrine syndrome type 1 (APECED hepatitis), or drug-induced. See also -liver-kidney microsomal antibodies, liver-specific antigens. 

Liver-kidney microsomal antibodies (LKM). Autoantibodies directed against cytochrome P450 and uridine diphosphate (UDP)-glucuronosyltransferase (UGT) antigens typically found in patients... 

AIH is associated with the presence of liver- and nonliver-related autoantibodies m plasma. These are helpful in diagnosis, but are not likely to be the cause of liver injury. The most important antibodies for diagnosis include antinuclear antibody (ANA), antismooth muscle antibody (ASMA), and antiliver-kidney microsomal antigen type 1 (LKMi). A variety of other autoantibodies are found frequently in AIH, some of which are found in other disorders. A summary of the most common autoantibodies, their associations, and their molecular targets (when known) is given... 

Similar in vivo labeling studies contributed other important information they demonstrated that the rate of protein synthesis was different in different tissues. Although the proteins of liver, kidney, intestinal mucosa, spleen, pancreas, bone marrow, and testicles are rapidly labeled, labeling is slow in muscle, brain, erythrocyte, and skin. Within a given tissue, some proteins are labeled faster than others. In the pancreas, the hydrolytic enzymes incorporate amino acids more rapidly than other proteins. The label appears sooner in some cell fractions than in others. After in vivo administration of antigens, 50% of the antibodies can be recovered in the microsomal fraction only a few minutes after injection. It was also shown that under conditions of net protein synthesis, labeled amino acids injected in mice are first recovered in the microsomes, then in the supernatant, and later in the zymogen granules of the pancreas. 

Fig. 5.13 Antibodies (type 1) against microsomes from liver and kidney (LKM) or against endoplasmic reticulum (AER). Antigenic substrate kidney. Green fluorescence of the cytoplasm, particularly in the third segment of proximal tubules. The distal tubules are negative (40 x) (134)...

In the reconstituted systems the reductase proved not to be specific for a particular cytochrome P450. The enzyme from liver could reduce the to-monooxygenase from kidney and vice versa and its antibody was effective in inhibiting the NADPH-mediated cytochrome c reduction in spleen microsomes. 

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