Aspartate aminotransferase-immunoglobulin complexes in patients with chronic liver disease

Tameda, Masahiko; Shiraki, Katsuya; Ooi, Kinue; Takase, Koujirou; Kosaka, Yoshitane; Tameda, Yukihiko

doi:10.3748/wjg.v11.i10.1529

Cited by 22 publications

(18 citation statements)

References 19 publications

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“…In general, autoantibodies which form macroanalyte complexes are not believed to be disease-causing although cases associated with autoimmune disorders have been described [16,17] and reports suggesting an association between the presence of autoantibodies against cTnI and cardiomyopathy have been published [18][19][20]. Based on current evidence, the main problem caused by a circulating macroanalyte is that it leads to multiple, possibly invasive, investigations in search of a cause.…”

Section: Introductionmentioning

confidence: 99%

High incidence of macrotroponin I with a high-sensitivity troponin I assay

Warner

Marshall

2016

Clinical Chemistry and Laboratory Medicine (CCLM)

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Background:Cardiac troponin is the preferred biomarker of myocardial injury. High-sensitivity troponin assays allow measurement of very low levels of troponin with excellent precision. After the introduction of a high-sensitivity troponin I assay the laboratory began to receive enquiries from clinicians about clinically discordant elevated troponin I results. This led to a systematic investigation and characterisation of the cause.Methods:Routine clinical samples were measured by the Architect High Sensitive Troponin-I (hsTnI) and the VITROS Troponin I ES assays (VitrosTnI). Results that were elevated according to the Architect but not the VITROS assay (Group 1) or results elevated by both assays but disproportionately higher on the Architect (Group 2) were re-analysed for hsTnI after re-centrifugation, multiple dilutions, incubation with heterophilic blocking reagents, polyethylene glycol (PEG) precipitation, and Protein A/G/L treatment. Sephacryl S-300 HR gel filtration chromatography (GFC) was performed on selected specimens.Results:A high molecular weight complex containing immunoreactive troponin I and immunoglobulin (macrotroponin I) was identified in 5% of patients with elevated hsTnI. Patients with both macrotroponin and myocardial injury had higher and longer elevation of hsTnI compared with VitrosTnI with peaks of both macrotroponin and free troponin I-C complex on GFC.Conclusions:Circulating macrotroponin I (macroTnI) causes elevated hsTnI results with the Architect High Sensitive Troponin-I assay with the potential to be clinically misleading. The assay involved in this investigation may not be the only assay affected by macrotroponin. It is important for laboratories and clinicians to be aware of and develop processes to identify and manage specimens with elevated results due to macrotroponin.

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Section: Introductionmentioning

confidence: 99%

High incidence of macrotroponin I with a high-sensitivity troponin I assay

Warner

Marshall

2016

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…We examined whether the healthy control group and the patient groups differed in the amounts of ALTIgA complex and found that the HCC and LC groups had higher amounts of the ALT-IgA complex than the other groups [median A 450 , 1.7 (interquartile range, 1.4 -1.9) vs 1.3 (interquartile range, 0.9 -1.6)] (see figure in the online Data Supplement); however, the concentrations of the ALT-IgA complex were significantly higher in all of the patient groups compared with the control group (all P Ͻ 0.05). Recently, several reports described high IgA concentrations in serum and a high incidence of IgA nephropathy in LC patients and indicated that the amount of aspartate aminotransferaseIgA complexes increased as liver disease progressed (12,13 ). Other modifications of serum ALT, such as glycation or fragmentation by proteolysis, could inhibit the interaction of ALT with a cofactor or substrate or could convert the functional dimeric protein to a monomeric form (8,14 ).…”

Section: Resultsmentioning

confidence: 99%

Abundance of Immunologically Active Alanine Aminotransferase in Sera of Liver Cirrhosis and Hepatocellular Carcinoma Patients

Kim

et al. 2009

Clinical Chemistry

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Background: Although alanine aminotransferase (ALT) is a widely used indicator of liver function, ALT enzymatic activity may not always reflect the degree of liver damage. Improved methods or approaches would be useful. Methods: Monoclonal antibodies (mAbs) to ALT were generated to develop a sandwich enzyme immunoassay system. We used an immunoassay to measure ALT mass concentration and a common biochemical analyzer to assay ALT enzymatic activity in serum samples from patients with liver diseases and healthy individuals. The results from the 2 methods were compared and analyzed by ROC curve analysis. Results: The ALT sandwich enzyme immunoassay system demonstrated reliable performance in linearity, recovery, and imprecision studies. The ALT activity assay exhibited a higher diagnostic accuracy in acute hepatitis (AH) patients, but the ALT immunoassay exhibited higher sensitivity and specificity in patients with chronic liver diseases. The areas under the ROC curve for ALT mass and enzymatic activity were 0.82 and 0.98, respectively, in AH, 0.99 and 0.52 in hepatocellular carcinoma (HCC), and 0.94 and 0.45 in liver cirrhosis (LC). Serum samples from HCC and LC patients had higher amounts of ALT–immunoglobulin complexes [median A450, 1.7 (interquartile range, 1.4–1.9)] than the other groups [1.3 (interquartile range, 0.9–1.6)]. Conclusions: Our analysis of sera from the HCC and LC patient groups revealed considerable amounts of immunologically active but catalytically inactive ALT. The amount of the ALT–immunoglobulin complex increased with the severity of the liver disease. The 2-site immunoassay method may be useful in the differential diagnosis of some causes of liver disease.

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“…encontró presencia de macro-AST en 90% de los pacientes con carcinoma hepatocelular, 41,8% de pacientes con hepatitis crónica, 62% de pacientes con cirrosis y en 66% de las hepatitis alcohólicas 6,18 . Los macro-complejos enzimáticos se pueden medir con distintas técnicas.…”

Section: Elevación Aislada De La Aspartato-aminotransferasa (Ast)unclassified

Aumento aislado y sostenido de aspartato aminotransferasa por presencia de macroenzimas: Caso clínico

Bustamante¹,

Arab²,

Terc³

et al. 2016

Rev. méd. Chile

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We report an asymptomatic 23-year-old woman with an isolated and persistent increase in serum levels of aspartate aminotransferase (AST). An extensive work up including laboratory and image testing revealed no abnormalities thus suggesting the presence of macro-AST. A polyethylene glycol (PEG) precipitation assay was performed and confirmed the presence of macro-AST.( Rev Med Chile 2016; 144: 1078-1082

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Aspartate aminotransferase-immunoglobulin complexes in patients with chronic liver disease

Cited by 22 publications

References 19 publications

High incidence of macrotroponin I with a high-sensitivity troponin I assay

High incidence of macrotroponin I with a high-sensitivity troponin I assay

Abundance of Immunologically Active Alanine Aminotransferase in Sera of Liver Cirrhosis and Hepatocellular Carcinoma Patients

Aumento aislado y sostenido de aspartato aminotransferasa por presencia de macroenzimas: Caso clínico

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