γ-interferon test
The γ-interferon test (English: Interferon-γ release assays (IGRA) ) is a test procedure for the diagnosis of tuberculosis . Highly specific antigens from Mycobacterium tuberculosis , the causative agent of tuberculosis, stimulate memory cells in the test tube ( in vitro ) . When they recognize the antigens because they have already been presented during an infection, they increasingly produce various messenger substances, including interferon-γ ( interferons ). This can be measured in the cell supernatant.
Methods
The first generations of interferon-γ tests used PPD ( Purified Protein Derivatives ) as an antigen. Subsequently, ESAT-6 ( early secreted antigenic target ) and CFP-10 ( culture filtrate protein ) were used as single antigens . Newer generations use combinations of several antigens, since better results in terms of sensitivity and specificity are achieved.
The “QuantiFERONTB® Gold In-Tube” from the Australian manufacturer Cellestis and the “T SPOT ™” have been available in Germany since 2004. TB ”from the British manufacturer Oxford Immunotec Limited.
The “QuantiFERONTB® Gold In-Tube” uses the antigens ESAT-6 ( early secreted antigenic target ), CFP-10 ( culture filtrate protein ) and Tb7.7 for stimulation. They are formed in the early phase of infection and are just as little produced by most of the so-called non-tuberculosis mycobacteria (NTM) than by the vaccine strain Mycobacterium bovis-BCG . This explains the very high degree of discrimination of the test between real tuberculosis infections and those caused by atypical mycobacteria or immunity acquired through vaccination. After the antigens have been incubated with the fresh whole blood at 37 ° C, the concentration of γ-interferon in the cell supernatant can be measured using a so-called ELISA (enzyme-linked immunosorbent assay). Any unspecific γ-interferon found in a negative sample must be subtracted from this value.
Alternatively, the “T SPOT ™. TB ”, a so-called ELISPOT (enzyme-linked immunospot assay), the number of γ-interferon-producing cells can be determined. This method is more time-consuming compared to the ELISA, but provides more valid results for immuno-incompetent and small children. In addition, there is no gray area with this method.
Because IGRAs are more expensive and technically more complex than the Mendel-Mantoux test, the WHO advises in its 2011 policy paper against using IGRAs as a means of health policy in countries with limited financial resources.
rating
sensitivity
In various studies on patients with active, bacteriologically confirmed tuberculosis, the sensitivity was between 82 and 100%. If a tuberculin skin test (TST) was carried out in parallel , the γ-interferon test was more sensitive. But in the case of fresh tuberculosis or a weak immune system, the γ-interferon test can also be false-negative .
Specificity
In a group of BCG-vaccinated persons, the specificity of the γ-interferon test was clearly superior with 98% compared to 35% with the TST. According to previously unpublished data, the very high specificity in children would also enable a differentiation from infections caused by atypical mycobacteria, which play a special role at this age. In view of the extremely low incidence of tuberculosis in German children (<2: 100,000), screening does not make sense because a false positive rate of only 2% results in far more false than correct test failures.