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We recently received this request: https://loinc.org/95971-8/ --- SARS CoV-2 stimulated gamma interferon [Presence] in Blood. 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 IFNg Response Release Assay, which has been modeled in the LB domain in the TB-TAUG.both TB TAUGs V1 and V2.

The IFNG Response test toward M. Tuberculosis is modeled in the LB domain, in the TB-TAUG v2.0 as modeling looks like the following:

ELISA:

ELISPOT:

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TB-TAUG V1 Modeling looks like the following:

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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?
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. Tb? - NHOID is NOT appropriate and should NOT be used here because in this case, the subject of study is NOT the Mycobacterium tuberculosis itself but whether someone has been previously exposed to M. Tuberculosis, by examining whether there is heightened Interferon-gamma activation. A positive result does not mean the person is currently infected with Mycobacterium tuberculosis, it may mean that the person had been previously infected by, or vaccinated against M. Tuberculosis. NHOID is used when you know the microorganism or a reference strain is present in the testing sample. M. Tuberculosis is mapped to ISCNDAGT to indicate that the stimulating agents are TB antigens.
   

3. Info
   title When should NHOID be used?
   NHOID, defined by the Non-host Organism Identifiers (OI) domain, should be used to map microorganisms that have been either experimentally determined in the course of a study or are previously known (e.g., lab strains used as reference in the study). In other words, NHOID is used when the study subject is the microorganism, and when the microorganism is present in the testing sample. In vaccine efficacy studies, a subject’s post-immunization sera is often incubated with a microbial strain of interest, where the functional capacities of the vaccine-induced antibodies are measured through whether the antibodies can effectively stop (from infection), neutralize, and kill the study microorganism of interest, in vitro. Examples of such tests include microneutralization, hemagglutination inhibition, and opsonophagocytic-killing assays. These are tests which measure the direct effect of the antimicrobial antibodies on the microorganism; therefore, said microorganism is the study subject and should be mapped to NHOID. Tests that measure and quantify a subject's cellular and humoral immune responses to a microorganism or a vaccination agent—such as measurements of activated cytokine- or antibody–secreting cells, or cytokine response assays (e.g., interferon gamma response test)—are biological measurements about the human subject. Because these are not assessments about the microorganism itself, NHOID should not be used.

CP domain has developed a new standard variable called Test Condition Agent/CNDAGT (CP Specification), which is used to represent stimulating agents, like the values in ASSYAG above, should this variable be added to LB, or IS?  StatuscolourGreentitleTeam agrees
4. Lastly, Interferon-Gamma Response Assay is a classic immunological test, is it correct to map this to the LB domain?
   
   1. Can we model this in the IS domain, see example dataset below. Yes -

      Status
      colour Green title Team Agrees

   2. If we model this test in IS, how do we distinguish it from the INFg test in lab. If we are running a routine lab test looking for IFNg levels it goes to LB. If we are running IFNg challenge/response test toward a specific, known microorganism then it goes to IS, you will also need to use the ISCNDAGT variable to house the challenge agent name. Yes-

      Status
      colour Green title Team Agrees

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1. Lastly, 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 changes in the actual level of IFN-g or number of IFN-g 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-g release immune response, and this belong in the IS domain.
   • Model in MB, if the IGRA test is used to indicate whether a subject has ongoing or prior infection of a specific pathogen. In this case, you are doing a microbial detection test based on the interpretation of the IFN-g release immune response. You do NOT care or the lab does not provide you with actual results of the IFN-g related changes. 
2. 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

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1. IFN-g. The example had a LBTEST value of interferon gamma, this is wrong,

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1. and should be changed to "Interferon gamma-secreting Cells"

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1. .

TB TAUG V1 Remodel in the IS domain

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T-Cell ELISPOT:

Dataset wrap

Dataset2 hi1style yellow hi1 column ISBDAGNT tableid IS table 1 Row NHOID STUDYID DOMAIN USUBJID SPDEVID ISSEQ ISGRPID ISTESTCD ISTEST ISMSCBCE ISTSTCND ISCNDAGT ISTSTDTL ISORRES ISORRESU ISSTRESC ISSTRESN ISSTRESU ISSPEC ISMETHOD ISDTC 1 ABC IS ABC-01-201 ABC002 1 1 CYKSCCL Cytokine-secreting Cells INTERFERON GAMMA WITHOUT STIMULATING AGENT 1 SFC/10^6 PBMC 1 1 SFC/10^6 PBMC PERIPHERAL BLOOD MONONUCLEAR CELLS ELISPOT 2013-08-26 2 Mycobacterium tuberculosis ABC IS ABC-01-201 ABC002 2 1 CYKSCCL Cytokine-secreting Cells INTERFERON GAMMA WITH STIMULATING AGENT CFP-10 13 SFC/10^6 PBMC 13 13 SFC/10^6 PBMC PERIPHERAL BLOOD MONONUCLEAR CELLS ELISPOT 2013-08-26 3 Mycobacterium tuberculosis ABC IS ABC-01-201 ABC002 3 1 CYKSCCL Cytokine-secreting Cells INTERFERON GAMMA WITH STIMULATING AGENT ESAT-6 17 SFC/10^6 PBMC 17 17 SFC/10^6 PBMC PERIPHERAL BLOOD MONONUCLEAR CELLS ELISPOT 2013-08-26 4 ABC IS ABC-01-201 ABC002 4 1 CYKSCCL Cytokine-secreting Cells INTERFERON GAMMA WITH STIMULATING AGENT Mitogen 30 SFC/10^6 PBMC 30 30 SFC/10^6 PBMC PERIPHERAL BLOOD MONONUCLEAR CELLS ELISPOT 2013-08-26 5 Mycobacterium tuberculosis ABC IS ABC-01-201 ABC002 5 1 CYKSCCL Cytokine-secreting Cells INTERFERON GAMMA InterpretationINTERPRETATION Positive Positive PERIPHERAL BLOOD MONONUCLEAR CELLS ELISPOT 2013-08-26

MBTEST = M. tuberculosis IFN Gamma Response - OK to deprecate

Note: in the future when we see this type of requests, recommend people to either model in IS or MB, but this is an "or" situation where you do not expect to see both IS and MB. It is one or the other.

POSITIVE POSITIVE ELISPOT
Dataset wrap
Name mb
Dataset2 hi1style yellow hi1 column ISBDAGNT tableid IS table 1 Row STUDYID DOMAIN USUBJID SPDEVID MBSEQ MBTESTCD MBTEST MBTSTDTL MBORRES MBSTRESC MBMETHOD MBDTC LOINC 1 ABC MB ABC-01-201 ABC002 1 MTB Mycobacterium tuberculosis Interpretation Detected Detected Interferon Gamma Release Assay 2013-08-26 71773-6

Dataset wrap
Name di
Dataset2 hi1style yellow hi1 column ISBDAGNT tableid IS table 1
Dataset wrap
Dataset2 hi1style yellow hi1 column ISBDAGNT tableid IS table 1 Row Row	STUDYID	DOMAIN	SPDEVID	MBSEQ	DIPARMCD	DIPARM	DIVAL
1	ABC	DI	ABC002	1	DEVTYPE	Device Type	INTERFERON-GAMMA RELEASE ASSAY
2	ABC	DI	ABC002	2	TRADENAM	Trade Name	T-Spot.TB

ELISA:

2013-08-26

NHOID STUDYID DOMAIN USUBJID SPDEVID ISSEQ ISGRPID ISTESTCD ISTEST ISTSTCND ISCNDAGT ISTSTDTL ISORRES ISORRESU ISSTRESC ISSTRESN ISSTRESU ISSPEC ISMETHOD ISDTC 1 ABC IS ABC-01-201 ABC001 1 1 IFNG Interferon Gamma UNSTIMULATED Nil, no antigen WITHOUT STIMULATING AGENT 1.3 IU/mL 1.3 1.3 IU/mL PLASMA ELISA 2013-08-26 2 Mycobacterium tuberculosis ABC IS ABC-01-201 ABC001 2 1 IFNG Interferon Gamma STIMULATED WITH STIMULATING AGENT Mycobacterium tuberculosis ESAT-6, CFP-10, TB 7.7 6.2 IU/mL 6.2 6.2 IU/mL PLASMA ELISA 2013-08-26 3 ABC IS ABC-01-201 ABC001 3 1 IFNG Interferon Gamma STIMULATED WITH STIMULATING AGENT Mitogen 0.9 IU/mL 0.9 0.9 IU/mL PLASMA ELISA 2013-08-26 4 ABC IS ABC-01-201 ABC001 4 1 IFNG Interferon Gamma

Detection

Positive

Positive

PLASMA

ELISA

INTERPRETATION

POSITIVE

POSITIVE

ELISA

2013-08-26