Liver and Gastric Parietal Cell Antibodies, LKS Substrate ( ANA, AMA, SMA, LKM, GPC )

Immunology

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Description

The autoimmune liver screen utilises a composite tissue block of mouse liver, kidney and stomach to detect anti-nuclear antibodies, gastric parietal cell antibodies, anti-mitochondrial cell antibodies and liver kidney microsomal antibodies all of which can be used to assess for autoimmmune liver disease. Gastric Parietal Cell ( GPC ) antibodies are associated with atrophic gastritis ( type A ) which is associated with pernicious anaemia ( PA ). They are found in 90% of patients with pernicious anaemia and are considered by some to be an appropriate screening test, although this is only true for certain population groups such as caucasians in Europe [1]. It has been shown that African Americans with pernicious anaemia often have negative GPC antibodies but positive intrinsic factor antibodies [4]. Intrinsic factor antibodies should be used as a confirmatory test if the GPC pattern is masked by another antibody pattern on immunofluorescence ( for example, anti-mitochondrial antibodies ) [1]. The availability of Intrinsic factor immunoassays have largely replaced GPC as a screen with better predicitive values. B12 levels are not directly related to the level of GPC antibodies [1]. GPC antibodies are more common in females and increase with age. They are also associated with autoimmune thyroid disease and other autoimmune conditions such as type 1 diabetes and Sjogren's syndrome [1,2] in which PA is also more common. Anti-nuclear antibodies ( ANA ) are positive in 95-100% of patients with systemic lupus erythematosus ( SLE ), 40-70% of Sjogren's patients and 60-80% of scleroderma patients [3]. A postive ANA can also be present in patients with primary biliary cirrhosis ( PBC ), Raynauds, rheumatoid arthritis, dermatomyositis, mixed connective tissue disease and other autoimmune conditions. They are however found in low and high titre in many non-autoimmune conditions and are not diagnostic in themselves. Smooth Muscle Antibodies ( SMA ) can be found in the normal adult population, but high titres occur in patients with viral infection ( such as hepatitis B and adenovirus ) and autoimmune chronic active hepatitis. Low titres are common and not strongly associated with autoimmunity. Liver-Kidney Microsome ( LKM ), antibodies which stain cytoplasm of hepatocytes and proximal renal tubules, are rare, specific and found in a subgroup of ANA negative patients with autoimmune chronic active hepatitis ( AICAH ) - mainly type 2 AICAH. Three types of LKM have been described, LKM-1, LKM-2, LKM-3. LKM-1 can be determined by IIF, however LKM-2 and LKM-3 show similar staining patterns. Type 1 AICAH is characterised by SMA and ANA. Anti-Mitochondrial Antibodies ( AMA ) of M2 type are strongly associated with PBC although they can also be seen in other conditions such as rheumatoid arthritis, scleroderma, Sj�gren's syndrome and rare cases of AICAH. Different types of AMA are described, based on antigen specificity, designated on a numeric basis: M1 to M9. The AMA associated with PBC is usually M2a or M2b. Not all can be typed by IIF. Specific immunoassays are available for target antigens but are not often routinely used.

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Indications

ANA - connective tissue disease such as systemic lupus erythematous ( SLE ) and primary biliary cirrhosis ( PBC ). AMA - PBC. GPC - Pernicious anaemia ( PA ). SMA/LKM - Autoimmune chronic active hepatitis ( AICAH ).

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Sample Type

2mL Serum ( Gel 5mL Yellow tube ). Requests from outside Sheffield: Transport at ambient temperature via Royal Mail or Courier.

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Reference Range

Normal result = Negative ( at 1/100 dilution ).

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Turnaround Time

Within 5 days

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Testing Frequency

Twice Weekly

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References

Khan S, et al. Limiited value of testing for intrinsic factor antibodies with negative gastric parietal cell antibodies in pernicious anaemia. J Clin Pathol. 2009. 62:439-441. [Ref 1]
Bogdanos DP, Invernizzi P, Mackay IR. Autoimmune liver serology: current diagnostic and clinical challenges. World Journal of Gastroenterology. 2008. 14( 21 ): 3374-3387.
Muratori L, et al. Anti-mitochondrial antibodies and other antibodies in primary biliary cirrhosis; diagnostic and prognostic value. 2008. 12( 2 ): 261-276.
Hennes EM, et al. Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology. 2008. 48( 1 ):169-176.
Sinclair D. Clinical and laboratory aspects of thyroid autoantibodies. Ann Clin Biochem. 2006. 43:173-183.[Ref 2]
Czaja AJ. Autoantibodies in autoimmune liver disease. Advance in Clinical Chemistry. 2005. 40:127-164.
Kavanagh A, et al. Guidelines for clinical use of antinuclear antibody test and tests for specific autoantibodies to nuclear antigens. American College of Pathologists. Arch Pathol Lab Med. 2000. 124( 1 ):71-81. [Ref 3]
Carmel R. Reassessment of the relative prevalences of antibodies to gastric paretal cell and to intrinsic factor in patients with pernicious anaemia: Influence of patient age and race. Clin Exp Immunol. 1992. 89( 1 ):74-77. [Ref 4].

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