Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
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        Anti-smooth Muscle Antibody test, blood
      
Anti-smooth muscle antibody (ASMA or ASM)

Inova ANA, ANCA, and liver disease serology decision trees HERE. Our gastroenterologists have ordered this non-liver-specific serology test as a screen for autoimmune hepatitis (AIH)...generally accepted as a marker of autoimmune hepatitis (AIH). If positive, patient is more likely to get a liver biopsy. But, it is said not to be a sensitive AIH screen & can be negative (because it waxes & wanes in low-grade AIH cases [L09-9472?]). And, as shown below, it may not be specific for true & pure AIH. Also, there is a school of thought that if any plasma cells can be seen in the portal areas in a liver biopsy case with hepatocyte injury features (even just mild elevation of SGPT/ALT), there is concern for at least a low-grade AIH-like component of hepatic injury so as to justify a course of steroid "AIH-component-in-mind" therapy. In a potential serological search for confirming evidence of an AIH primary or component injury, there are other named and as-yet-un-named autoantibodies (which may or may not be reflected in elevated serum IgA or IgM elevations or SPE beta-gamma bridging).

Being directed biologically at smooth muscle actin microfilaments, this auto-antibody is directed against actin, troponin, and tropomyosin. We have used animal-tissue substrate at a beginning dilution of patient's serum of 1:20. The use of animal tissue avoids interference from human HLA and/or blood group Abs that may occur if human substrate were used. Incidental Abs may show up in this system such as APCA, ANA, ARA, ABBA, anti-canalicular Ab, anti-liver cell membrane Ab, anti-ribosomal Ab, and anti-granular-leukocyte (polys). And, ASMA may unexpectedly & incidentally show up in the smooth muscle component of other IFA substrates, such as with anti-endomysial (CN09-87...she was ASMA 1:80). At a starting dilution of patient's serum of 1:20, there are many "false positives" for ASMA at this low-titre level. So, "reactive" but, by convention, not "positive" is <1:40; and "a nonspecific positive titer" is 1:40-1:160, quite possibly reflective of a minor but treatable auto-immune component complicating some other primary hepatidite. We have documented instances of levels >1:160 that were not AIH...so, liver biopsy findings are crucial to proper total case interpretation prior to heavy medical therapy.

ASMA can be seen in infectious mononucleosis & other viral infections, SLE, in breast & ovarian carcinoma, in melanoma. It can also be seen in about 50% of cases of PBC cirrhosis (overlap?), alcoholic related cirrhosis, and cases of biliary duct obstruction.

A 1972 paper providing results of community screening for ASMA found positivity in 1.2% of "normal" people under age 40 and in 3.5% of those over 70 years of age3.

As of 2011: additional IFA antibodies & a large variety of additional EIA-type antibodies has become more easily commercially available so that we may be able to use a decision-tree type workup through LML. (CHART HERE)

F-actin: Actin filaments are made by polymerization of globular actin (G-actin) subunit monomer into microfilaments forming F-actin & thence into actin. F-actin antibodies (IgG) have been shown to have greater sensitivity and specificity for autoimmune liver disease than anti-smooth muscle antibodies4. BUT, F-actin can still be false positive [L12-7423]. Here is an example (slow loading) decision tree HERE.

The non-organ-specific antibodies: AMA (a number of antimitochondrial antibodies = M1 or MIT-1 for SLE, Sjogrens, progressive systemic sclerosis; M2 or MIT-2 for PBC; M3 or MIT-3 for pseudolupus syndrome; M4 or MIT-4 for PBC; M5 or MIT-5 for non-specific collagenoses; M6 or MIT-6 seen in variety of disorders & Iproniazide-induced hepatitis; M7 or MIT-7 in acute myocarditis and cardiomyopathies; M8 or MIT-8 in PBC; and M9 or MIT-9 in PBC & other forms of hepatitis); ANA (a "basket" of many specific antinuclear antibodies); LKM (a number of liver-kidney-microsomal antibodies: LKM-1 in AIH [directed against the antigen cytochrome P450 2D6, also known as CYP2D6] & LKM-2 in drug induced hepatitis & LKM-3 [directed against the family of 1 UDP glucuronosyl transferases, also known as UGT1A] in chronic hepatitis D); antiactin antibody; ASMA (anti-smooth-muscle antibody); LP (anti-liver-pancreas antibody); and pANCA antibody.

Liver-specific antibodies: ASGPR (anti-asialoglycoprotein receptor antibody directed against asialoglycoprotein receptor); LSP (liver-specific lipoprotein); LC1 (anti-liver cytosol type 1 antibody directed against formiminotransferase cyclo deaminase [FTCD]); LMA (liver membrane antigen); and SLA (anti-soluble liver antigen antibody directed against tRNP(SER)Sec).

implying hepatocyte-component-directed auto-antibodies: ANA, ASMA, LKM-1, F-actin, SLA, LP, LC1, LKM-3, atypical p-ANCA.

implying biliary-component-directed auto-antibodies: AMA, PDH-E2 (antibody against human pyruvate dehydrogenase complex enzyme 2), MS Ep(MIT3), gp210, sp100, atypical p-ANCA.

other: LM (liver-only microsomal antibody against CYP1A2) in APECED hepatitis (autoimmune polyendocrinopathy candidias ectodermal dystrophy6).

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Associations with undetectable ASMA ab:

  • normalcy.
  • extra-hepatic biliary obstruction1.
  • cases of liver biopsy "concern for AIH component " when biopsy shows some portal plasma cells...but could this non-reactivity be a false negative?
Associations with elevated levels of ASMA ab:

  • autoimmune (chronic active) hepatitis:  always think of AIH and of Wilson's in a young adult; 50-80% of cases1, 70% at >1:1002; our lab considers >1:160 to be "significant serologic evidence, suspicious for autoimmune hepatitis, especially if liver biopsy contains lots of plasma cells".
  • primary biliary cirrhosis (PBC) 0-50% of cases1
  • cryptogenic cirrhosis 0-1% of cases1    
  • viral hepatitis 1-2% of cases1
  • suggests a minor autoimmune component when present & plasma cells present along with some other primary hepatidite.
  • AIH-complication on top of another liver disease (I believe that many/most in the chart below had OTHER obvious liver disease but a more minor & complicating AIH component, an angle that I...EBS...did not become familiar with until later in 2009).
some of our case examples with elevated ASMA:
case number clinical result/comments
LMC-01-4435 38 y/o BF with LFTs elevated ASMA .1:320 & <1:1280; Bx hepatic sarcoidosis, cirrhosis and mild acute ascending pericholangitis; AMA, ANCA, ANA all neg.
LMC-01-273 39 y/o M with LFTs elevated & COPD ASMA 1:160; ANA, AMA, anti-LKM all neg.; Bx showed central congestion & sclerosis
LMC-02-81 61 y/o F with LFTs elevated & elevated ferritin ASMA 1:80; ANA & AMA neg.; Bx NASH with cirrhosis
LMC-02-713 54 y/o F high LFTs  ASMA 1:160; ANA & AMA neg; IgG 3680: AIH, Bx
LMC-02-747 48 y/o F elev. LFTs ASMA 1:320, ANA 1:1280; AIH, Bx
LMC-02-4640 61 y/o F high LFTs ANA neg; ANCA neg; ASMA 1:320; AMA 1:1280; PBC-AIH overlap, Bx
LMC-02-6428 38 y/0 F elevated LFTs & family Hx cirrhosis ANA 1:80, speckled; AMA, neg; ASMA 1:40; anti-LKM neg; Bx NASH without fibrosis
LMC-02-8257 55 y/o F SOB & elevated LFTs ANA 1:160 homo. & ASMA 1:160; Bx metastatic small cell ca.
LMC-02-7628 50 y/o F elevated ALT, AST, GGTP ANA 1:640 speckled; ASMA 1:80; Bx normal
LMC-03-3790 79 y/o M acute pancreatitis ASMA 1:320 Bx has mild portal reactive "hepatitis"
L07-6555 19 y/o F elevated LFTs ALT 387; ASMA "pos"; Bx has cirrhosis w/ grade III severe chronic hepatitis c/w AIH.
L09-1613 29 y/o M elevated LFTs ALT 214 & AST 72; ASMA 1:640; Bx w/subtle patchy hepatocyte swelling & rare acidophil body.

REFERENCES:

  1. A B C's of Interpretive Laboratory Data, 2nd Ed., Seymour Bakerman, MD, PhD, 1984
  2. Lex. Med. Lab. procedure manual and its references as of 7/01
  3. Rochman H, et. al., textbook: Clinical Pathology in the Elderly...,, 1988, 222 pages.
  4. ARUP F-actin file HERE.
  5. from MedScape web site, "Diagnostic and Therapeutic Implications of Bile Duct Injury in Autoimmune Hepatitis", HERE.
  6. Am. Assoc. for Study of Liver Diseases (AASLD) 2010 "AASLD Practice Guidelines: Diagnosis and Management of AIH"...all about serology tests HERE.
  7. Beland Kathie, et. al., "Anti-LC1 autoantibodies in patients with chronic hepatitis C virus infection", Journal of Autoimmunity 22(2):159-166, March 2004 HERE
  8. Kanel GC & Korula J, Atlas of Liver Pathology, 2nd Ed., 2005, 355 pages.
  9. EUROIMMUN's Liver Mosaic 16 page handout 4/28/2010, English version with references.
(posted June 2001; latest update 25 June 2011; latest addition 6/15/2013)
 
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