Interferon-gamma release assay: Difference between revisions

Latest revision as of 14:56, 15 April 2024

Background

In vitro test that assess for a cell-mediated immune response to tuberculosis antigens
- Usually early secreted antigenic target 6 (ESAT-^) and culture filtrate protein 10 (CFP-10)
Used for diagnosis latent tuberculosis infection
Unclear utility in children under 5 years
Levels often decline after treatment for LTBI or active tuberculosis, but remain positive
In Canada, we have two tests available:
- QuantiFERON-TB Gold Plus (QFT-Plus): an in-tube ELISA whole-blood test of ESAT-6 and CFP-10, uses 2 tubes (the second designed to stimulate CD8 T-cells), and is reported in IU/mL
- T-SPOT.TB: a spot ELISA assay performed on separated peripheral blood mononuclear cells, using ESAT-6 and CFP-10, and is reported in the number of spots compared to a control

Interpretation

QuantiFERON-TB Gold Plus

Reports the IU/mL of 4 tubes: negative control (which assesses baseline interferon activity), antigen 1, antigen 2, and mitogen control (to assess their immune response in general)
Reported as positive if either antigen 1 or 2 is ≥0.35 above the control tube

Tube (IU/mL)				Result
Nil	TB1 - nil	TB2 - nil	Mitogen - nil	Result
≤8	≥0.35 and ≥25% of nil	any	any	positive
	any	≥0.35 and ≥25% of nil	any	positive
	<0.35, or ≥0.35 and <25% of nil	<0.35, or ≥0.35 and <25% of nil	≥0.5	negative
	<0.35, or ≥0.35 and <25% of nil	<0.35, or ≥0.35 and <25% of nil	<0.5	indeterminate
>8	any			indeterminate

There appears to be a dose-response relationship between the IGRA result and risk of progression to active TB, with the risk rising from 0 to 5 and then plateauing by about 101

T-SPOT.TB

Reports the number of spots in the antigen wells compared to a control well
Positive it at least 8 more spots in the antigen wells

False Positives

The antigens cross-react with some species of non-tuberculous mycobacteria, particularly Mycobacterium marinum, Mycobacterium kansasii, Mycobacterium szulgai, and Mycobacterium flavescens

References

^ Jorge R. Ledesma, Jianing Ma, Peng Zheng, Jennifer M. Ross, Theo Vos, Hmwe H. Kyu. Interferon-gamma release assay levels and risk of progression to active tuberculosis: a systematic review and dose-response meta-regression analysis. BMC Infectious Diseases. 2021;21(1). doi:10.1186/s12879-021-06141-4.

@@ Line 1: / Line 1: @@
+== Background ==
-* Test for diagnosis [[latent tuberculosis infection]]
+* ''In vitro'' test that assess for a cell-mediated immune response to [[tuberculosis]] antigens
+** Usually early secreted antigenic target 6 (ESAT-^) and culture filtrate protein 10 (CFP-10)
+* Used for diagnosis [[latent tuberculosis infection]]
 * Unclear utility in children under 5 years
 * Levels often decline after treatment for LTBI or active tuberculosis, but remain positive
+* In Canada, we have two tests available:
-*
+** QuantiFERON-TB Gold Plus (QFT-Plus): an in-tube ELISA whole-blood test of ESAT-6 and CFP-10, uses 2 tubes (the second designed to stimulate CD8 T-cells), and is reported in IU/mL
+** T-SPOT.''TB'': a spot ELISA assay performed on separated peripheral blood mononuclear cells, using ESAT-6 and CFP-10, and is reported in the number of spots compared to a control
+== Interpretation ==
+=== QuantiFERON-TB Gold Plus ===
+* Reports the IU/mL of 4 tubes: negative control (which assesses baseline interferon activity), antigen 1, antigen 2, and mitogen control (to assess their immune response in general)
+* Reported as positive if either antigen 1 or 2 is ≥0.35 above the control tube
+{| class="wikitable"
+! colspan="4" |Tube (IU/mL)
+! rowspan="2" |Result
+|-
+!Nil
+!TB1 - nil
+!TB2 - nil
+!Mitogen - nil
+|-
+| rowspan="4" |≤8
+|≥0.35 and ≥25% of nil
+|any
+| rowspan="2" |any
+| rowspan="2" |positive
+|-
+|any
+|≥0.35 and ≥25% of nil
+|-
+| rowspan="2" |<0.35, or ≥0.35 and <25% of nil
+| rowspan="2" |<0.35, or ≥0.35 and <25% of nil
+|≥0.5
+|negative
+|-
+|<0.5
+| rowspan="2" |indeterminate
+|-
+|>8
+| colspan="3" |any
+|}
+* There appears to be a dose-response relationship between the IGRA result and risk of progression to active TB, with the risk rising from 0 to 5 and then plateauing by about 10[[CiteRef::ledesma2021in]]
+=== T-SPOT.''TB'' ===
+* Reports the number of spots in the antigen wells compared to a control well
+* Positive it at least 8 more spots in the antigen wells
+=== False Positives ===
+* The antigens cross-react with some species of [[non-tuberculous mycobacteria]], particularly [[Mycobacterium marinum]], [[Mycobacterium kansasii]], [[Mycobacterium szulgai]], and [[Mycobacterium flavescens]]
 [[Category:Tuberculosis]]