Simultaneous evaluation of diagnostic marker utility for enzootic bovine leukosis

Abstract

BackgroundEnzootic bovine leukosis (EBL) is a disease of cattle caused by bovine leukemia virus (BLV). More than 60% of BLV-infected cattle remain subclinical and are thus referred to as aleukemic (AL) cattle. Approximately 30% of infected cattle show a relatively stable increase in the number of B lymphocytes; these cattle are termed persistent lymphocytosis (PL) cattle. A small percentage of infected cattle develop BLV-induced B cell lymphoma (EBL) and are called EBL cattle. Due to the increase in the number of BLV-infected cattle, the number of EBL cattle has featured a corresponding increase over recent years in Japan. Several diagnostic criteria for EBL (e.g., enlarged superficial lymph nodes, protrusion of the eye, increased peripheral blood lymphocyte, etc.) are used for on-farm diagnosis and antemortem tests at slaughterhouses. Since the slaughter of EBL cattle for human consumption is not allowed, on-farm detection of EBL cattle is important for reducing the economic loss incurred by farms. Therefore, establishing new diagnostic markers to improve the efficiency and accuracy of the antemortem detection of EBL cattle is a critical, unmet need. To simultaneously evaluate the utility of candidate markers, this study measured the values of each marker using the blood samples of 687 cattle with various clinical statuses of BLV infection (EBL, PL, AL and non-infected cattle).ResultsSensitivity (Se) and specificity (Sp) were highest for the serum thymidine kinase (TK) followed by the serum lactate dehydrogenase (LDH) isozyme 2. The number of peripheral blood lymphocytes and proviral load in peripheral blood had the lowest Se and Sp. The values of all markers other than TK were influenced by the sex of the tested cattle.ConclusionsAlthough tLDH and its isozymes (LDHs) may be influenced by the sex of the tested cattle, the high accuracy of TK and LDH2 as well as accessibility and simplicity of the protocol used to measure these enzymes recommend the utility of TK and LDHs for EBL cattle detection. Using these markers for screening followed by the application of existing diagnostic criteria may improve the efficiency and accuracy of EBL cattle detection on farms, thereby contributing to the reduction of economic losses in farms.

Diagnosis and Early Prediction of Lymphoma Using High-Throughput Clonality Analysis of Bovine Leukemia Virus-Infected Cells

“…PVL has been considered to be a significant marker in EBL diagnosis ( 17 ). However, the sensitivity and specificity of EBL diagnosis by PVL in blood samples was very poor in this study, which is consistent with another previous study ( 20 ). Although elevation of PVL appear to be a necessary step in the development of EBL, it is not a suitable diagnostic marker for the development and early diagnosis of EBL.…”

Lymphoma cells are circulating in blood of Enzootic Bovine Leukosis and clonality value of virus-infected cells is a useful information for the diagnostic test

“…Asymptomatic and non-EBL cattle showed high proviral load as EBL cattle (Fig. 3A)(17). Thus, it is not so useful to know the quantity of infected cells but the clonality of infected cells is critical to know the disease status of EBL (Fig.…”

“…Several candidate markers detected using blood tests has been reported to be useful to diagnose EBL. Serum total lactate dehydrogenase (LDH) and thymidine kinase (TK) tends to be elevated in EBL cattle (17). Since EBL is a B-cell-lymphoma, immunophenotypic analysis of peripheral blood is also reported as a candidate blood test (18).…”

Time course changes in peripheral B-cell clonality in a Japanese Black bull with enzootic bovine leukosis

“…Thirty-eight percent of peripheral lymphocytes were found to be atypical. Higher activities of onset markers for lymphoma, including thymidine kinase (38.9 U/L), total LDH (11,850 U/L), and LDH isozyme-2 (4,432 U/L) and -3 (2,406 U/L), were observed, suggesting the development of lymphoma [ 3 , 8 ].…”

“…In such cases, it would be difficult to definitively diagnose EBL without necropsy. However, thymidine kinase and LDH activities, which are markers for the onset of lymphoma [ 3 , 8 ], were very high and predicted the onset of lymphoma. The usefulness of these biomarkers was reconfirmed in this case.…”