Interferon-Gamma Response Assays -updates from TB-TAUG V1 and V2

We recently received this request: SARS CoV-2 stimulated gamma interferon [Presence] in Blood (https://loinc.org/95971-8/). We also received requests for the following LOINC codes: 95974-2, 95972-6, and 95973-4. Upon further research on all 4 LOINC codes, they are referring to the IFN-y Release Assay (IGRA), which has been modeled in the LB domain in both TB-TAUGs V1 and V2.

TB-TAUG v2.0 modeling looks like the following - 

ELISA:

ELISPOT:

TB-TAUG v1.0 modeling looks like the following - 

There are several concerns with this modeling:

1. There are two ways of modeling Interferon Gamma Release Assay based on TB-TAUG V1 and V2, does V2 modeling replace V1 modeling? Are they modeling the same thing?
   • Email sent to Jon to see if V2 model is intended to replace V1 model.
   • Email from Jon 2022-07-07: I was indeed part of the team but have no recollection of this example or any of the discussions around how it evolved. However, I think it’s safest to go with TBv2; it must have been updated for a reason. I would deprecate the original TESTCD, especially if you’ve already been denying additional requests for tests following that same structure. 
2. Where do you show that this challenge assay is done against M. Tuberculosis (or any microbe of interest, like SARS-CoV-2), where do you map M. Tuberculosis?
   • Map to NHOID.
     
3. Interferon-Gamma Release Assay (IGRA) is a classic immunological test, is it correct to map this to the LB domain as per the TB TAUGs? What recommendations do we give to our users in the future when we see a request such as: SARS-CoV-2 stimulated gamma interferon, https://loinc.org/95971-8/?
   
   • Model in IS, if you need to report the detailed changes in the actual levels of IFN-y or number of IFN-y secreting cells, the stimulating and control agents used in the assay, and a "summary interpretation" result of positive, negative, or indeterminate, etc. In this case, you are testing and recording the explicit changes in the subject/host's IFN-y release immune response, and this belongs in the IS domain. A derived MB record may be created to show that M. Tuberculosis is identified/detected based on the interpretation of the IS dataset.
   • or...
   • Model and report in MB ONLY, if you do NOT care or the lab does not provide you with actual details and results of the subject/host's IFN-y levels related changes. In this case, you are doing a microbial detection/identification test based on the interpretation (MBTSTDTL) of the INTERFERON GAMMA RELEASE ASSAY (MBMETHOD), see here: https://loinc.org/71773-6/.
4. The ELISPOT LB example in the TB-TAUG V2 has an error, the unit is reported in SFC/10^6 PBMC so you are counting the number of cells that secrete IFN-y. The example had a LBTEST = interferon gamma, this is wrong, the test should be measured in Cells, and should be changed to ISTEST = Cytokine-secreting Cells, where ISMSCBCE = Interferon Gamma.

TB-TAUG v2.0 Remodel in the IS domain

Model in IS, if you need to report changes in the actual level of IFN-y or number of IFN-y secreting cells, the stimulating and control agents used in the assay, and a "summary interpretation" result of positive, negative, or indeterminate, etc. In this case, you are testing and recording the explicit changes in the IFN-y release immune response, and this belong in the IS domain.

Example 1: Measure INF-y using T-Cell ELISPOT

The MB data below are derived records from the IS dataset above, the identification and diagnosis of Mycobacterium tuberculosis are interpretations based on the IFNy responses test results above.

Note: there is an existing, pre-coordinated MBTEST = M. tuberculosis IFN Gamma Response/C92241, (also from TB TAUG V1), this test will be deprecated because the modeling is incorrect. The MB/IS team will not publish tests similar to C92241 in the future, and we recommend users to model this type of tests using the below structure. Please be aware that you may also ONLY report the MB records below alone, if you do not care or the lab does not provide you with the actual results and details of the subject's IFN-y levels related changes.