Cellular fatty acid-binding proteins: Their function and physiological significance

The present invention provides methods for the identification and use of diagnostic markers for differential diagnosis of diseases and/or conditions. In a various aspects, the invention relates to methods and compositions able to determine the presence or absence of one, and preferably a plurality, of diseases or conditions that exhibit one or more similar or identical symptoms. Such methods and compositions can be used to provide assays and assay devices for use in determining the disease or condition underlying one or more non-specific symptoms exhibited in a clinical setting.

Markers for differential diagnosis and methods of use thereof

Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight cytoplasmic protein and present abundantly in the myocardium. When the myocardium is injured, as in the case of myocardial infarction, low molecular weight cytoplasmic proteins including H-FABP are released into the circulation and H-FABP is detectable in a blood sample. We have already developed a direct sandwich-ELISA for quantification of human H-FABP using two distinct types of monoclonal antibodies specific for human H-FABP. In this study we investigated the clinical validity of H-FABP as a biochemical diagnostic marker in the early phase of acute myocardial infarction (AMI). To evaluate the diagnostic usefulness of H-FABP in the early phase of AMI, blood samples were obtained from the following patients within 12 hours after the appearance of symptoms, and serum levels of H-FABP were compared with those of conventional diagnostic markers, such as myoglobin and creatine kinase isoenzyme MB (CK-MB). Blood samples were collected from patients with confirmed AMI (n=140), patients with chest pain who were afterwards not classified as AMI by normal CK-MB levels (non-AMI) (n=49) and normal healthy volunteers (n=75). The serum concentration of H-FABP was quantified with our direct sandwich-ELISA. The concentration of myoglobin mass was measured with a commercial RIA kit. The serum CK-MB activity was determined with an immuno-inhibition assay kit. The overall sensitivity of H-FABP, within 12 hours after the appearance of symptoms, was 92.9%, while it was 88.6% with myoglobin and 18.6% with CK-MB. The overall specificity of H-FABP was 67.3%, while it was 57.1% with myoglobin and 98.0% with CK-MB. The diagnostic efficacy rates with these markers were 86.2% (H-FABP), 80.4% (myoglobin) and 39.2% (CK-MB), respectively. The diagnostic validity of H-FABP was further assessed by receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) of H-FABP was 0.921, which was significantly greater than with myoglobin (AUC: 0.843) and CK-MB (AUC: 0.654). These parameters, such as sensitivity, specificity, diagnostic efficacy and diagnostic accuracy, obtained for patients with chest pain within 3 hours and/or 6 hours after the onset of symptoms were almost the same as those for patients within 12 hours after symptoms. H-FABP is more sensitive than both myoglobin and CK-MB, more specific than myoglobin for detecting AMI within 12 hours after the onset of symptoms, and shows the highest values for both diagnostic efficacy and ROC curve analysis. Thus, H-FABP has great potential as an excellent biochemical cardiac marker for the diagnosis of AMI in the early phase.

Human heart-type cytoplasmic fatty acid-binding protein (H-FABP) for the diagnosis of acute myocardial infarction. Clinical evaluation of H-FABP in comparison with myoglobin and creatine kinase isoenzyme MB.

Heart fatty-acid-binding protein (FABP) is a small cytosolic protein that is abundant in the heart and has low concentrations in the blood and in tissues outside the heart. It appears in the blood as early as 1.5 h after onset of symptoms of infarction, peaks around 6 h and returns to baseline values in 24 h. These features of H-FABP make it an excellent potential candidate for the detection of acute myocardial infarction (AMI). We review the strengths and weaknesses of H-FABP as a clinically applicable marker of myocyte necrosis in the context of acute coronary syndromes.

/pdf/do-we-need-additional-markers-of-myocyte-necrosis-the-jvnm7w4i3b.pdf

Do we need additional markers of myocyte necrosis: the potential value of heart fatty-acid-binding protein

We compared the diagnostic utility of serum concentrations of human heart-type cytoplasmic fatty acid-binding protein (H-FABPc), myoglobin, and their ratio for the early diagnosis of acute myocardial infarction (AMI) in 104 healthy volunteers and 165 patients at admission within 6 h of the onset of chest pain. The ROC curves of the H-FABPc [0.946, 95% confidence interval (CI) = 0.913–0.979] and myoglobin (0.895, 95% CI = 0.846–0.944) between patients with AMI and healthy volunteers were significantly greater than the area under the ratio of myoglobin to H-FABPc (0.823, 95% CI = 0.765–0.881). In 165 patients, the sensitivity (81.8%, 95% CI = 74.2–89.4%), specificity (86.4%, 95% CI = 78.1–94.6%), and predictive accuracy (83.6%, 95% CI = 78.0–89.3%) of H-FABPc >12 μg/L in diagnosing AMI were significantly higher than those of myoglobin, and were similar to those of the combination of H-FABPc >12 μg/L and the ratio ≤14. We conclude that H-FABPc is a more sensitive and specific marker than myoglobin for the early diagnosis of AMI, and that their ratio cannot give a clear advantage over the measurement of H-FABPc alone.

/pdf/serum-concentrations-of-myoglobin-vs-human-heart-type-vmkxkhey4d.pdf

Serum concentrations of myoglobin vs human heart-type cytoplasmic fatty acid-binding protein in early detection of acute myocardial infarction

Human heart-type cytoplasmic fatty acid-binding protein in serum and urine during hyperacute myocardial infarction.

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Human heart-type cytoplasmic fatty acid-binding protein in serum and urine during hyperacute myocardial infarction.