Heiko Schotte1, Peter Willeke2, Johanna Schmalhorst3, Bernhard Schlüter3. 1. Niels-Stensen-Kliniken, Osnabrück, Germany. 2. Medizinische Klinik und Poliklinik D, Universitätsklinikum Münster, Germany. 3. Centrum für Laboratoriumsmedizin, Universitätsklinikum Münster, Germany.
Abstract
BACKGROUND: A serologic hallmark of autoimmune hepatitis (AIH) type 1 are anti-smooth muscle autoantibodies (ASMA) with specificity for filamentous actin (F-actin; AAA (anti-actin antibodies)), traditionally detected by indirect immunofluorescence (IFT) using rat liver, kidney, and stomach tissue sections as substrates. However, IFT is a subjective method requiring an experienced investigator. Therefore, a more objective technique for the detection of AAA may be a helpful diagnostic tool. METHODS: In a retrospective study with cross-sectional design, we evaluated AAA detected by an enzyme immunodot blot (IDB; Liver5 IgG BlueDot, D-tek, Mons, Belgium). Serum samples of patients with AIH type 1 (n = 47) and specified controls (n = 142) were included. For comparison, standard IFT was applied to rat LKS (liver, kidney, stomach) triple tissue sections. RESULTS: IDB readings were done by two independent investigators (92% concordance). The diagnostic sensitivity of the AAA-IDB was 70%, compared to 51% of AAA-IFT (n.s.). The diagnostic specificity of AAA-IDB was significantly lower compared to AAA-IFT (76% vs. 94%; P < 0.0005). Correspondingly, the positive predictive value (49% vs. 75%; P < 0.05) and positive likelihood ratio (2.9 vs. 8.5) differed significantly. Neither prescreening for ANA or ASMA, nor the exclusion of infectious hepatopathies resulted in a significantly better diagnostic performance of the IDB. CONCLUSION: Compared to standard IFT, testing for AAA via IDB did not result in a significantly better diagnostic performance for AIH type 1. A blot with higher antigen binding specificity may be more functional.
BACKGROUND: A serologic hallmark of autoimmune hepatitis (AIH) type 1 are anti-smooth muscle autoantibodies (ASMA) with specificity for filamentous actin (F-actin; AAA (anti-actin antibodies)), traditionally detected by indirect immunofluorescence (IFT) using rat liver, kidney, and stomach tissue sections as substrates. However, IFT is a subjective method requiring an experienced investigator. Therefore, a more objective technique for the detection of AAA may be a helpful diagnostic tool. METHODS: In a retrospective study with cross-sectional design, we evaluated AAA detected by an enzyme immunodot blot (IDB; Liver5 IgG BlueDot, D-tek, Mons, Belgium). Serum samples of patients with AIH type 1 (n = 47) and specified controls (n = 142) were included. For comparison, standard IFT was applied to rat LKS (liver, kidney, stomach) triple tissue sections. RESULTS: IDB readings were done by two independent investigators (92% concordance). The diagnostic sensitivity of the AAA-IDB was 70%, compared to 51% of AAA-IFT (n.s.). The diagnostic specificity of AAA-IDB was significantly lower compared to AAA-IFT (76% vs. 94%; P < 0.0005). Correspondingly, the positive predictive value (49% vs. 75%; P < 0.05) and positive likelihood ratio (2.9 vs. 8.5) differed significantly. Neither prescreening for ANA or ASMA, nor the exclusion of infectious hepatopathies resulted in a significantly better diagnostic performance of the IDB. CONCLUSION: Compared to standard IFT, testing for AAA via IDB did not result in a significantly better diagnostic performance for AIH type 1. A blot with higher antigen binding specificity may be more functional.
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