2. introduction
The liver is an important organ with responsibility
for many critical functions (for example,
metabolism of protein and fats, storage, bile acid
production and detoxification (toxic drugs &
chemicals). Inability to perform these functions
leads to liver disease. In this section, autoimmune
liver disease (such as autoimmune hepatitis (AIH),
primary biliary cirrhosis (PBC), primary sclerosing
cholangitis (PSC), and autoimmune
cholangiopathy and overlap syndromes)
3. Autoimmune liver diseases
A variety of clinical signs and symptoms may be
associated with the liver disease and the
evidence of autoimmune involvement is
characterized by chronic progressive
inflammation and hyper gamma globulinaemia
and the presence of specific high tire auto-
antibodies is often evident.
4. Primary Biliary Cirrhosis (PBC):
Anti-mitochondrial antibodies (AMA) are
associated with this disease and affects
older females with an incident of 90%. The
cause is unknown but it is thought that
infection might be a trigger. The most
common target for these antibodies is M2
antigen, the pyruvate dehydrogenase
complex. A number of the subunits of the
pyruvate dehydrogenase may be targeted.
5. Autoimmune hepatitis (AIH)
This affects about 90% of younger female patients and
is categorised by seropositivity for antinuclear antibody
(ANA) and/or smooth muscle or antibodies to liver
kidney microsomes (LKM). Type 1 AIH is associated with
high titre of ANA and /or AMA, whereas type 2 AIH is
associated with LKM. There are several antigens
identified associated with AIH, for example, liver
kidney microsome, liver cytosolic (LC-1), liver
cytokeratine, glutathione-S-transferase, soluble liver
antigen, actin in smooth muscle and ANA.
9. Note:
Anti-mitochondria antibodies (AMAs) are observed on rat or
mouse kidney sections .Cytoplasmic speckling can also be
seen in liver. The antibodies are important in the
investigation of liver disease such as chronic active hepatitis,
autoimmune hepatitis and PBC. Mitochondria antibodies can
be detected in patient serum years before symptoms
manifest. The assay is 95% specific for the disease. In PBC
the mitochondria antigen is pyruvate dehydrogenase. A
simple ELISA assay can be performed to confirm the
presence of M2 antibodies that are relevant to PBC.
10.
11. Other mitochondrial antibodies can also be viewed by
immunofluorescence. The clinical significance of these
antibodies is described in Table 1.
12. Liver-kidney microsomal antibodies (LKM) bind to both cytochrome
P450 in hepatocytes and proximal renal tubes in rodent tissue .Three
types have been characterized. LKM-1 is associated with 2a and 2b
autoimmune chronic active hepatitis. LKM-2 and LKM-3 are associated
with drug induced hepatitis and hepatitis-δ respectively.
13. Immunofluorescence pattern of LKM1 antibodies on liver (left) and
kidney (right). Staining of proximal tubules can be observerved on the
kidney, whereas distal tubules remain unstained.
14. Revision notes:
Several subtypes of anti-liver-kidney microsomal antibodies (LKM) are known.
LKM-1 antibodies associated with autoimmune chronic active hepatitis recognize P450 2D6, a
cytochrome P450 mono-oxygenase. The frequent association of anti-LKM-1 antibodies and
hepatitis C virus (HCV) infections and the probable existence of an infectious and autoimmune
form of anti-LKM-1-associated hepatitis, requiring different therapeutically strategies,
necessitates the exact determination of anti-LKM-1 specificities.
The recently recognized association of anti-LKM-1 antibody and HCV infection was confirmed
by the results of this study. In anti-HCV and HCV-RNA-positive patients with anti-LKM-1
antibodies there was a preponderance of males with higher mean age and lower antibody
titres. The results support the hypothesis of the existence of an autoimmune as well as an
infectious (HCV triggered) subgroup of anti-LKM-1-positive hepatitis.
15. Remember: Liver/kidney
microsomal antibody type 1
(LKM1) is the marker of type
2 autoimmune hepatitis
(AIH) and is detected in up to
6% of patients with hepatitis
C virus (HCV) infection.
16. The presence of LKM1
in the plasma
membrane was
investigated by
indirect
immunofluorescence.
17. TEST
Screening test for detection of IgG autoantibodies against Smooth muscle,
Mitochondria and Liver Kidney Microsomal antigens.
Clinical Indications:
Primary Biliary Cirrhosis
Autoimmune hepatitis
Please note: Low titre antibodies may be found in normal
people and in a variety of diseases without an autoimmune
basis, such as inflammation and cancer. The prevalence of
these antibodies increases with age, but in general titres
of greater that 1/80 are often significant disease
indicators. Low or absent titres do not exclude disease in
the presence of relevant clinical features
18. Specimen
Serum
Volume
7 ml
Container
Red top tubeVacutainer red top
Collection
Samples should be transported to the laboratory immediately
Lab Handling
Aliquot and store at 4°C prior to testing and at -20°C or below for 3
months after receipt
19. Causes for Rejection
Unlabelled/inadequately labelled sample
Inadequately completed request form
Delay in sample reaching laboratory
Reference Range
Sera are screened at a dilution of 1/20 (paediatric samples 1/10). In general titres
greater or equal to 1/80 are often significant. Samples found to be anti mitochondrial
positive will be referred for M2 antibodies. Samples found to be positive at 1/20 may
be referred for other Liver Specific Antibodies if clinical details and pattern observed
indicate testing.
Below are listed the most common reported antibodies and their main clinical
association:
Mitochondrial antibody - Primary Biliary Cirrhosis, autoimmune thyroiditis and
Sjogren's syndrome.
Smooth muscle antibody - autoimmune hepatitis, viral infections, SLE and RA.
Liver Kidney Microsomal Antibody- Autoimmune and drug induced hepatitis infections
