Elsevier

Journal of Hepatology

Volume 41, Issue 4, October 2004, Pages 677-683
Journal of Hepatology

Special article
Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group

https://doi.org/10.1016/j.jhep.2004.08.002Get rights and content

Introduction

The diagnosis of autoimmune hepatitis (AIH) has been advanced by the criteria developed by the International Autoimmune Hepatitis Group (IAIHG) [1], [2]. A critical component of these criteria is detection by indirect immunofluorescence (IIF) of autoantibodies to components of the nuclei (anti-nuclear, ANA), smooth muscle (SMA) and liver kidney microsomes type 1 (anti-LKM-1). Detection not only assists in the diagnosis but also enables discrimination between two distinct subtypes of the disease [1], [2], AIH-1 and AIH-2. The differing serological reactivities for the two types (ANA, SMA vs anti-LKM-1) are virtually mutually exclusive; in the rare exceptions with ‘double positive’ serology, the clinical expression resembles AIH-2 [3], [4]. Also, consideration is needed of ‘overlap’ syndromes [5], [6], in particular types of cholangiopathy with autoimmune serological expressions. The relatively low prevalence of autoimmune liver diseases and the operator dependency of immunofluorescence, which still remains the mainstay of liver diagnostic autoimmune serology, explain the lack of agreement between laboratories on the frequency of particular reactivities in different liver diseases, particularly the less frequent specificities such as anti-LKM-1. Perceived inaccuracy of the methodology apparently led influential authors to suggest (misleadingly) that assessment of autoantibodies be disregarded in the diagnosis of AIH because of the low sensitivity and specificity of relevant serological tests [7]. This view also may have been motivated by assignment of autoantibody testing to commercial laboratories and use of kit-based semi-automated systems often with little contact between laboratory and clinician to assist in interpretation of results. Moreover, kit-based commercial assays may have been validated only ‘in-house’, such that the performance characteristics would not necessarily be available to the end-user. The problems that do exist between laboratory reporting and clinical interpretation of the serological results depend in part on insufficient standardisation of the basic tests, a problem common to autoimmune diagnostic serology in general, and in part on a degree of unfamiliarity of some clinicians with disease expressions of AIH. In regard to standardisation, a lead has been taken by the diabetes community in encouraging use of standardised methods by establishing ongoing serum exchange workshops since 1986 with calibrated reference sera containing autoantibodies to autoantigens relevant to type 1 diabetes mellitus [8], [9], [10]. Consequently, editors of major journals of diabetes now expect, in reports that cite reactivities of autoantibodies, that assays have been validated under international workshop conditions. Accordingly, the IAIHG established an internationally representative committee to define guidelines and develop procedures and reference standards for more reliable testing.

Although concerned with specific serological reactivity, emphasis is given to the importance for diagnosis and for monitoring treatment of a raised level of immunoglobulin (Ig) G measured by standard procedures, as noted in the IAIHG criteria.

Section snippets

Autoantibody testing by indirect immunofluorescence

The basic technique for the routine testing of autoantibodies relevant to AIH is IIF on a freshly removed rodent (usually rat) multi-organ substrate panel that should include kidney, liver and stomach. This allows for detection of ANA, SMA, anti-LKM-1 as well as anti-mitochondrial antibody (AMA), and also antibodies to liver cytosol type 1 (anti-LC1). For sera positive at the screening stage, further examination is required to assess the pattern of nuclear staining, by use of HEp2 cells, or to

Concluding remarks

Detection of autoantibodies plays a pivotal role in the diagnosis of liver disorders with an autoimmune pathogenesis and may be a useful tool in monitoring disease activity. However, both the laboratory personnel and the clinician need to become more familiar with the interpretation of the liver autoimmune serology to derive maximum benefit for the patient. Akin to what has already been achieved for other autoimmune diseases, especially type 1 diabetes, this can only be obtained through

Acknowledgements

We thank: Dimitrios Bogdanos, Ian McFarlane, Giorgina Mieli-Vergani, Yun Ma, Luigi Muratori and Senga Whittingham for helpful comments.

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    The authors are the members of the committee for autoimmune serology of the International Autoimmune Hepatitis Group. DV is the chairman.

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