‘Simple’ QuantiFERON‐TB Gold Blood Test May Help in Diagnosing HLH

‘Simple’ QuantiFERON‐TB Gold Blood Test May Help in Diagnosing HLH

QuantiFERON-TB Gold by Quiagen, a widely used blood test, was found to be helpful in diagnosing hemophagocytic lymphohistiocytosis (HLH), a study reports.

“This simple diagnostic test could really support pediatricians” in diagnosing children with the immune cell disease, the researchers wrote.

The study, “QuantiFERON-TB Gold can help clinicians in the diagnosis of haemophagocytic lymphohistiocytosis,” was published in the British Journal of Haematology.

HLH is characterized by uncontrolled activation of macrophages and T-cells — two types of white blood cells present in the immune system. The overactivation of T-cells leads to the excessive production of a cytokine called interferon-gamma, known as IFN‐gamma. Of note, a cytokine is a small protein released by immune cells that helps them to interact with each other.

A wide range of symptoms — from fever and cytopenia, or low blood cell numbers, to liver impairment — are associated with HLH. Because these symptoms are similar to other conditions, it makes it more challenging for clinicians to properly diagnose this rare disease.

Other challenges in making a correct diagnosis are related to the lack of availability of some blood-based and genetic tests in many hospitals. Bone morrow biopsy can be used, however it is not considered a specific or even sensitive approach.

To fill these gaps, a team of researchers studied the possibility of using QuantiFERON-TB Gold, known as QFT‐G, as a diagnostic test for HLH.

QFT-G is a blood test that helps in the detection of Mycobacterium tuberculosis, the bacterium that causes tuberculosis, known as TB. As in people with HLH, T-cells of patients with tuberculosis respond to the infection by producing IFN‐gamma.

Since it is considered an IFN‐gamma release test, QFT-G is able to measure IFN‐gamma production in response to tuberculosis antigens, which are substances that can trigger an immune response in the body.

Now, researchers proposed that QFT-G also may detect IFN‐gamma levels in HLH patients, helping in the diagnosis of the disease.

In a six-year study, 13 children were diagnosed and treated for primary HLH (pHLH). During the diagnosis, and before being treated, all patients were tested for tuberculosis through two tests: QFT‐G and QFT‐G Plus.

IFN‐gamma levels were studied through a receiver‐operating‐characteristic (ROC) analysis, a method used to quantify how accurate a medical diagnostic test can be.

Results obtained were compared with three groups of patients: 13 children with acute leukemia, 13 with sepsis, and 13 healthy controls. Acute leukemia is a blood cancer characterized by low levels of IFN-gamma, while sepsis is a body’s severe response to an infection, in which IFN-gamma levels are typically increased.

The median IFN‐gamma levels in the HLH group was 2.49 international units per mL (IU/mL), significantly higher than those found in the leukemia, sepsis, and control groups. The median value in the leukemia group was 0.04 IU/mL, while that of the sepsis group was 0.07 IU/mL, and that of the control group was 0.036 IU/mL.

In all groups, ROC analysis on IFN‐gamma levels showed an area-under-the-curve — a measure of accuracy that varies between 0.5 and 1 — of 0.998. This tool also showed a high sensitivity and specificity of QFT-G in assessing INF‐gamma levels in these patients. The sensitivity, or the test’s ability to correctly identify patients with the disease, was 100%; the specificity, or its ability to correctly identify people without the disease, was 97.3%.

A previous study in mouse models of HLH showed typical blood alterations caused by IFN‐gamma, such as the reduction in the number of blood cells.

In their research now, the investigators found that increased IFN‐gamma levels measured through QFT‐G were related to a reduction in the number of neutrophils, a type of white blood cell typically decreased in HLH. Those findings further support the value of this test in diagnosing HLH.

“QFT‐G Plus, a diffuse and standardised blood test, in association with HLH‐04 criteria [diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis] could support clinicians in determining a diagnosis of pHLH with high sensitivity and specificity,” the researchers wrote.

The applicability of QFT‐G in diagnosing other conditions characterized by uncontrolled IFN-mediated immune responses may be questionable. However, the researchers underscored the importance of this test in hospitals where HLH diagnosis is still challenging.

“Although other interferonopathies [IFN-related disorders], genetic or acquired, such as systemic lupus erythematosus and juvenile dermatomyositis, could impair the specificity of the analysis, this simple diagnostic test could really support paediatricians in peripheral hospitals,” the researchers concluded.

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