The LKM-1 (Liver Kidney Microsomes type 1) test is a chemiluminescent immunoassay (CLIA), for use on IDS automated analyzers. It is used for the quantitative determination of specific IgG class antibodies directed against Liver Kidney Microsomes type 1, in human samples of serum or plasma (EDTA and Sodium Citrate).
Autoimmune Hepatitis (AIH) is a chronic inflammation of the liver of unknown origin, in which immune tolerance to hepatocytes is lost1. The disease is detected by the presence of a number of characteristic alterations from the histological point of view, when blood tests show the presence of gamma globulins and antibodies2. The disease is found mainly in females, both of paediatric and adult ages3. It is an autoimmune process and therefore is associated, sometimes, with other autoimmune disorders such as ulcerative colitis4 and Graves’ Disease5.
Autoimmune Hepatitis is classified according to the specific autoantibodies detected, which are, for type 1, principally represented by ANA (anti-nuclear) and SMA (anti-smooth muscle) antibodies; type 2 on the contrary is typified by LKM-1 (type 1 liver kidney microsomal) antibodies; type 3 is characterised by anti-SLA (soluble liver antigen) and anti-LP (liver pancreas antigen) antibodies.
The presence of anti-LKM autoantibodies was described for the first time in 19736. It was subsequently demonstrated that these are a heterogeneous family of autoantibodies and, depending on the target antigen, are classified in three types known as anti-LKM 1, 2 and 3. Cytochrome P4502D6 was identified as the autoantigen of the anti-LKM-1 antibodies7. Cytochrome P4502C9 and UDP-glucuronosyltransferase were later identified respectively as the targets of the anti-LKM-2 and anti-LKM-3 antibodies8. While anti-LKM-2 antibodies have been associated with drug-induced hepatitis, anti-LKM-1 antibodies have been associated with type 2 AIH and are a characteristic marker for this disease, not usually associated with the presence of ANA and/or ASMA of type 1 AIH.
However, anti-LKM-1 antibodies are not specific to type 2 AIH, in that they may be found in 5-10% of the patients with chronic HCV hepatitis9, even though the epitopes recognised in HCV patients are different from those recognised in patients suffering from type 2 AIH10,11.
Anti-LKM-1 antibodies are found in around 90% of patients with type 2 AIH8 and can be identified by the IFA test using sections of mouse liver and kidney tissue. It is also possible to test for anti-LKM-1 antibodies with indirect solid phase assays, using the recombinant protein CYP2D6 with high levels of sensitivity and specificity12,13.
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- Kachar R. and Fallon M. Diagnostic criteria for autoimmune hepatitis: what is the gold standard? Hepatology, 2010. 51(1): 350-1
- Ngu JH et al. Population-based epidemiology study of autoimmune disease: a disease of older women? J Gastroenterol Hepatol, 2010. 25(10): 1681-6.
- Navaneethan U. and Shen B. Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel disease. Inflamm Bowel Dis, 2010. 16(9): 1598-619.
- Nakamura H. et al. Prevalence of interrelated autoantibodies in thyroid diseases and autoimmune disorders. J Endocrinol Invest, 2008. 31(10): 861-5.
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- Gueguen M, Meunier-Rotival M, Bernard O, Alvarez F. Anti-liver kidney microsome antibody recognizes a cytochrome P450 from IID subfamily. J Exp Med 1988; 168: 801-6.
- Philipp T, Durazzo M, Trautwein C, Alex B, Straub P, Lamb JG, et al. Recognition of uridine diphosphate glucoronisyl transferases by LKM-3 antibodies in chronic hepatitis D. Lancet 1994; 344:578-81.
- Lenzi M, Ballardini G, Fusconi M, Cassani F, Selleri L, Volta U, et al. Type 2 autoimmune hepatitis and hepatitis C virus infection. Lancet 1990; 335:258-9.
- Declos-Valee JC, Hajaoui O, Yamamoto AM, Jacqz-Aigrin E and Alvarez F. Conformational epitopes on CYP2D6 are recognized by Liver/kidney microsomal antibodies. Gastroenterology 108: 467-470.1995.
- Dalekos GN, Wedemeyer H, Obermayer-Straub P, Kayser A, Barut A, Frank H and Manns MP. Epitope mapping of cytochrome P450 2D6 autoantigen in patients with chronic hepatitis C during alpha-interferon treatment. J. Hepatol. 30(3): 366-375.1999.
- Miyakawa H, Kikazawa E, Abe K, Kikuchi K, Fujikawa H, Matsushita M, Kawaguchi N, Morizane T, Ohya K, Kako M. Detection of anti-LKM-1 (anti-CYP2D6) by enzyme-linked immunosorbent assay in adult patients with chronic liver diseases. Autoimmunity, 1999;30(2):107-14
- Kekar N, Ma Y, Davies ET, Cheeseman P, Mieli-Vergani G, Vergani D. Detection of liver kidney microsomal type 1 antibody using molecularly based immunoassay. Journal of Clinical Pathology 2002;55(12): 906-909.