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IFN‐γ Release Assay Helps Diagnose Hemophagocytic Lymphohistiocytosis

By LabMedica International staff writers
Posted on 14 Aug 2020
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The QuantiFERON‐TB Gold Plus IFN‐γ release assay used to help diagnose hemophagocytic lymphohistiocytosis (Photo courtesy of Qiagen).
The QuantiFERON‐TB Gold Plus IFN‐γ release assay used to help diagnose hemophagocytic lymphohistiocytosis (Photo courtesy of Qiagen).
Hemophagocytic lymphohistiocytosis (HLH), either primary (pHLH, or Familiar, FHL) or secondary is a life‐threatening hyper‐inflammatory syndrome, characterized by massive and uncontrolled activation of macrophages and T cells, causing fever, cytopenia and liver dysfunction with coagulopathy.

The rarity of the HLH disease, along with its pleomorphic clinical presentation that mimics a number of different conditions (from severe infections to malignancies), makes the diagnosis challenging. Hemophagocytosis on bone morrow biopsy is the only histomorphological criterion, but, in itself, it is neither specific nor sensitive.

Hematologists at the Bambino Gesù Children's Hospital (Rome, Italy) diagnosed and treated 13 children with pHLH at the hospital from August 2014 to April 2020. During the diagnostic evaluation, all patients were tested for tuberculosis (TB) exposure through QuantiFERON‐TB Gold (QFT‐G, Qiagen, Hilden, Germany). The QuantiFERON test is an IFN‐γ release assay (IGRA), which measures IFN‐γ release in response to tuberculosis (TB)‐specific antigens. After centrifugation, plasma was harvested and enzyme‐linked immunosorbent assay (ELISA) tests were run.

The scientists reported that results obtained from the HLH group (all tests were reported as ‘Indeterminate’ because of high levels of IFN‐γ in the NIL Tube) were compared with three other groups of pediatric patients (matched for gender) with an available QFT‐G. These groups were: 13 children hospitalized for acute leukemia (AL) at time of diagnosis, 13 because of sepsis and 13 healthy controls (HC). The median (range) IFN‐γ levels at diagnosis/before starting treatment in the HLH group was 2.49 IU/mL (0.12–15.11) , significantly higher than those found in the AL, sepsis and HC groups, in which the median (range) value was 0.04 IU/mL (0.02–0.11) 0.07 (IU/mL 0.03–0.15) and 0.036 IU/mL (0.015–0.077) , respectively. A cut‐off value of 0.12 IU/mL had a sensitivity of 100% and a specificity of 97.3%.

The authors concluded that QFT‐G Plus, a diffuse and standardized blood test, in association with HLH‐04 criteria could support clinicians in determining a diagnosis of pHLH with high sensitivity and specificity. Although other interferonopathies, 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 pediatricians in peripheral hospitals. The study was published on July 26, 2020 in the British Journal of Haematology.

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