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Double Reactivity Against Actin and α-Actinin Defines a Severe Form of Autoimmune Hepatitis Type 1

Anti-filamentous actin antibodies characterize autoimmune hepatitis type 1 (AIH-1). Recently, the binding domain of α-actinin on actin was shown to be a predominant epitope. To test this reactivity, an anti-α-actinin enzyme-linked immunosorbent assay was developed, and positivity confirmed by Western blot. Anti-α-actinin antibody was found in 21/50 (42%) of AIH-1 patients, compared with 52/401 (12.9%) of liver disease control patients, and with 6/200 (6%) of blood donors. Anti-filamentous and anti-α-actinin activities were found specifically together in 66% of anti-filamentous-positive AIH-1 patients. This combination of specificities reflected clinical and histological disease activity, short duration and absence of treatment. Finally, using an actin-α-actinin complex assay, the binding of anti-filamentous actin to α-actinin-binding domain on actin was demonstrated, as well as that of anti-α-actinin on the actin-binding domain of α-actinin. Thus, the frequent combination of anti-filamentous and anti-α-actinin antibodies seems to be the hallmark of activity in AIH-1.

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    The IAHG score includes many parameters (sex, IgG increase, positivity for autoantibodies) including biopsy findings.

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ACKNOWLEDGMENTS

Many thanks are due to Cindy Séné and Simone Forest for secretarial assistance. The authors are also grateful to Prof. Peter M. Lydyard (UCL Medical School, London, UK) for his thoughtful review of the manuscript. This work has been supported in part by a grant (#2466) of the Research Committee, University of Thessaly.

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Correspondence to YOUINOU PIERRE.

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PAUL, G., GEORGIOS, D., JEAN-BAPTISTE, N. et al. Double Reactivity Against Actin and α-Actinin Defines a Severe Form of Autoimmune Hepatitis Type 1. J Clin Immunol 26, 495–505 (2006). https://doi.org/10.1007/s10875-006-9045-z

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KEY WORDS

  • autoimmunity
  • anti-smooth-muscle antibodies
  • active disease
  • binding domain
  • anti-ssDNA