Smooth muscle autoantibodies with F-actin specificity

Soares, Andrea Ferreira; Cunha, Rosário; Rodrigues, F.; Ribeiro, Helena

doi:10.1016/j.autrev.2009.02.023

Cited by 10 publications

(5 citation statements)

References 20 publications

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“…Antibodies to actin have high specificity for classical autoimmune hepatitis [15,17,20], but their assay has not been standardized [12,15,[17][18][19][137][138][139][140][141][142] and anti-actin are typically concurrent with SMA [11,17,18,143]. Whereas SMA can occur without anti-actin in 14% of patients with classical autoimmune hepatitis and be the sole marker of the disease in 5% [11], anti-actin is rarely (if ever) discovered alone [11,143].…”

Section: Diagnostic Autoantibodies Outside the Conventional Batterymentioning

confidence: 99%

Autoantibody-Negative Autoimmune Hepatitis

Czaja

2011

Dig Dis Sci

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Autoimmune hepatitis has a variable clinical phenotype, and the absence of conventional autoantibodies does not preclude its diagnosis or need for treatment. The goals of this review are to describe the frequency and nature of autoantibody-negative autoimmune hepatitis, indicate its outcome after corticosteroid treatment, and increase awareness of the diagnosis in patients with unexplained acute and chronic hepatitis. The frequency of presumed autoantibody-negative autoimmune hepatitis in patients with acute and acute severe presentations is ≤7%, and its frequency in patients with chronic presentations is 1-34%. Patients with acute presentations can have normal serum γ-globulin levels, centrilobular zone 3 necrosis, and low pre-treatment international diagnostic scores. Liver tissue examination is essential for the diagnosis, and hepatic steatosis can be a co-morbid feature. The comprehensive international scoring system can support but never override the clinical diagnosis pre-treatment, and non-standard serological markers should be sought if the clinical diagnosis is uncertain or the diagnostic score is low. A 3-month treatment trial with corticosteroids should be considered in all patients, regardless of the serological findings, and improvements have occurred in 67-87% of cases. Autoantibody-negative autoimmune hepatitis may be associated with an autoantibody outside the conventional battery; it may have a signature autoantibody that is still undiscovered, or its characteristic autoantibodies may have been suppressed or have a delayed expression. The pathogenic mechanisms are presumed to be identical to those of classical disease. Autoantibody-negative autoimmune hepatitis is an infrequent but treatable disease that must be considered in unexplained acute and chronic hepatitis.

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Section: Diagnostic Autoantibodies Outside the Conventional Batterymentioning

confidence: 99%

Autoantibody-Negative Autoimmune Hepatitis

Czaja

2011

Dig Dis Sci

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“…They can also be detected by indirect immunofluorescence of liver sections from rats chronically injected with phalloidin [65] or by assessing peritubular and glomerular structures in rat kidney [67]. Counterimmunoelectrophoresis with purified muscle actin [65] and enzyme immunoassays based on purified F-actin [64,[68][69][70] have also been advocated, and an actin-myosin functional assay in which actin activates meromyosin ATPase in skeletal muscle has been proposed [71]. A thermolabile F-actin depolymerizing factor may limit detection of the antibodies and may affect assay performance [72].…”

Section: Antibodies To Actinmentioning

confidence: 99%

Autoantibodies as Prognostic Markers in Autoimmune Liver Disease

Czaja

2010

Dig Dis Sci

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Certain autoantibodies in autoimmune liver disease have prognostic implications that are under-utilized and under-developed. The goals of this review are to indicate progress in characterizing the autoantibodies with prognostic connotations and to indicate the feasibility and importance of discovering other markers. Prime source and review articles in English were selected by a Medline search through 2010. Antibodies to soluble liver antigen, actin, liver cytosol type 1, asialoglycoprotein receptor, chromatin, cyclic citrullinated peptide, and uridine glucuronosyltransferases have been associated with the occurrence, severity, and progression of autoimmune hepatitis, and antibodies to Sp100, gp210, and centromere have had similar implications in primary biliary cirrhosis. Antibodies to soluble liver antigen have shown the most promise in autoimmune hepatitis as they have been associated with severe histological changes, long durations of treatment, relapse after drug withdrawal, and high frequency of liver failure. Antibodies to the nuclear rim pore protein, gp210, have shown the most promise in primary biliary cirrhosis as they have been associated with severe interface hepatitis, lobular inflammation, and progression to liver failure. The major limitations of the autoantibodies have been their lack of standardized assays, low negative predictabilities, and fluctuating levels. Performance parameters will improve as critical pathogenic pathways, comprehensive testing batteries, and standardized assays through international exchange workshops are developed. Progress has been made in identifying the serological markers of prognosis in autoimmune liver disease, and they promise to reflect critical disease mechanisms and enhance patient management.

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“… 162 Antibodies to actin have been associated with a higher frequency of death from hepatic failure or requirement for liver transplantation, but the prognostic implications of these antibodies are assay dependent. 27 , 30 , 162 , 173 – 176 Multiple assays for antiactin are available, but none has been incorporated into a standard diagnostic repertoire. 162 , 177 …”

Section: Serological Markersmentioning

confidence: 99%

Diagnosis and Management of Autoimmune Hepatitis: Current Status and Future Directions

2016

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Autoimmune hepatitis is characterized by autoantibodies, hypergammaglobulinemia, and interface hepatitis on histological examination. The features lack diagnostic specificity, and other diseases that may resemble autoimmune hepatitis must be excluded. The clinical presentation may be acute, acute severe (fulminant), or asymptomatic; conventional autoantibodies may be absent; centrilobular necrosis and bile duct changes may be present; and the disease may occur after liver transplantation or with features that suggest overlapping disorders. The diagnostic criteria have been codified, and diagnostic scoring systems can support clinical judgment. Nonstandard autoantibodies, including antibodies to actin, α-actinin, soluble liver antigen, perinuclear antineutrophil antigen, asialoglycoprotein receptor, and liver cytosol type 1, are tools that can support the diagnosis, especially in patients with atypical features. Prednisone or prednisolone in combination with azathioprine is the preferred treatment, and strategies using these medications in various doses can ameliorate treatment failure, incomplete response, drug intolerance, and relapse after drug withdrawal. Budesonide, mycophenolate mofetil, and calcineurin inhibitors can be considered in selected patients as frontline or salvage therapies. Molecular (recombinant proteins and monoclonal antibodies), cellular (adoptive transfer and antigenic manipulation), and pharmacological (antioxidants, antifibrotics, and antiapoptotic agents) interventions constitute future directions in management. The evolving knowledge of the pathogenic pathways and the advances in technology promise new management algorithms.

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Smooth muscle autoantibodies with F-actin specificity

Cited by 10 publications

References 20 publications

Autoantibody-Negative Autoimmune Hepatitis

Autoantibody-Negative Autoimmune Hepatitis

Autoantibodies as Prognostic Markers in Autoimmune Liver Disease

Diagnosis and Management of Autoimmune Hepatitis: Current Status and Future Directions

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