Anti LKM autoantibodies are differentiated from anti-mitochondrial antibodies using indirect immunofluorescence on stomach, kidney and liver tissue. Anti mitochondrial antibodies stain distal renal tubules whereas anti LKM antibodies do not – both stain proximal tubules. Anti LKM antibody is not a unique entity, it compasses 3 types of anti LKM antibody, namely anti LKM-1, anti LKM-2, and anti LKM-3 (δ agent). These can be distinguished from each other by unique immunofluorescent staining patterns.LKM-1 is found on cells in the third portion of the proximal renal tubules and on hepatocytes. (May also react with cells in bronchial, oesophageal and duodenal epithelium).
The immunofluorescent (IF) of anti LKM-2 is highly characteristic with liver centrilobular distribution in male mouse liver, heterogenity of the third portion of the proximal renal tubule and fetal liver negativity.
For detection of LKM-3, IF staining requires testing on human pancreas, this shows exocrine positivity, unlike any of the other anti LKM antibodies (Ab’s). LKM antibodies are found only in a small number of patients with autoimmune chronic active hepatitis and drug induced hepatitis, but are highly specific.
Anti-LKM-1 antibodies react with a protein identified as cytochrome P450 11D6. The 66kD band was shown to be NADPH cytochrome (P450) reductase – a microsomal enzyme catalysing the oxidase metabolism of a variety of drugs such as antihypertensives (debrisoquine), β blockers (bufuralol) and antiarmythmic drugs (sparlein). The autoantibodies are usually IgG and the levels appear to monitor disease activity.
Anti LKM-2 recognise human and rat P450 11C77.
Anti-LKM-3 recognise UDP-glucuronosyl transferase.
Identification of a sub-groups of patients with autoimmune chronic active hepatitis especially in children.
Antibodies recognising LKM-1 are found in a rare subset of patients with Type 2 chronic active hepatitis occurring usually in young patients. These autoantibodies are not associated with anti-nuclear or anti-smooth muscle antibodies which characterise the more common Type 1 chronic active hepatitis.CAH associated with anti LKM-1 is a very rare disease (5/1,000,000). It predominantly effects females (ratio F/M 8:1) and commonly occurs in childhood. This form of hepatitis is also strongly associated with other autoimmune diseases (esp insulin dependent diabetes, autoimmune thyroid disease and vitiligo) but other non-organ specific autoantibodies such as anti-smooth muscle antibodies are seldom found.
Anti LKM-2 was associated with tienilic acid induced hepatitis. Tienilic acid has since been withdrawn from the market.
Anti LKM-3 is found in chronic delta hepatitis.
LKM antibodies are also found in patients with chronic active hepatitis due to hepatitis C infection – usually in middle aged males of mediterranean extraction. Levels in true autoimmune disorders are usually greater than in virally induced disease.
Anti-LKM antibodies are occasionally found in adult patients who have no apparent liver disease. There is no clear correlation with any disease.
Serum Separator Tube (SST)
Indirect immunfluorescence mouse tissue (liver, kidney, stomach).
Assay range notes
Positive samples titre 1:40-1:640
5 – 7 days
Immunology The James Cook University Hospital