Currentblue cross blue shield - tennesseePolicy N/A

Immune Cell Function Assay Comm Bc Ma Dsnp G2098

This policy defines coverage determinations for immune cell function assays used to measure peripheral blood lymphocyte/T-cell function (eg, ATP levels, CD154 assays) for diagnosis or management, including proprietary tests (ImmuKnow, Pleximmune, iQue) and applicable CPT/HCPCS codes. It notes relation to Medicare/Medicaid and FDA status.

Policy Summary

Payerblue cross blue shield - tennessee

PolicyImmune Cell Function Assay Comm Bc Ma Dsnp G2098

Policy CodePolicy N/A

Change TypeNo material change

Effective Date

Next Review Date

Key ActionApply coverage criteria dependent upon the member's benefit coverage; if conflict with government (LCD/NCD) or state Medicaid policy, government policy prevails.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes were made in this update.

1Primary coverage position (not covered)

3Procedure codes referenced

Coverage Summary

This policy defines coverage determinations for immune cell function assays used to measure peripheral blood lymphocyte/T-cell function (eg, ATP levels, CD154 assays) for diagnosis or management, including proprietary tests ImmuKnow, Pleximmune, and iQue, and references applicable CPT/HCPCS procedure codes. Primary coverage stance: these assays are not covered (do not meet coverage criteria) due to insufficient published evidence of required clinical benefit.

Coding

Applicable Procedure Codes (referential)CPT|HCPCS

81560	Transplantation medicine (allograft rejection, pediatric liver and small bowel), measurement of donor and third-party-induced CD154+T-cytotoxic memory cells, utilizing whole peripheral blood, algorithm reported as a rejection risk score (Proprietary test: Pleximmune™; Lab/Manufacturer: Plexision, Inc.)
86352	Cellular function assay involving stimulation (eg, mitogen or antigen) and detection of biomarker (eg, ATP).
0018M	Transplantation medicine (allograft rejection, renal), measurement of donor and third-party-induced CD154+T-cytotoxic memory cells, utilizing whole peripheral blood, algorithm reported as a rejection risk score (Proprietary test: Pleximark; Lab/Manufacturer: Plexision, Inc.)
G2098	Policy title includes 'Comm Bc Ma Dsnp G2098' but code is not described in body.

Provider Actions & Billing Impact

Documentation Required

Benefit verification and regulatory precedence

Apply coverage criteria dependent upon the member's benefit coverage; if conflict with government (LCD/NCD) or state Medicaid policy, government policy prevails.

Billing Rule

Procedure code reporting guidance

Procedure codes listed in the policy are provided only as a general reference and may not be all-inclusive; laboratories should report the appropriate CPT/HCPCS code for the specific test performed.

81560
86352
0018M

Denial Risk

Coverage denial for immune cell function assays

Claims for immune cell function assays (eg, ImmuKnow®, Pleximmune™, Pleximar) do not meet coverage criteria and are not covered due to insufficient published evidence of required clinical benefit.

86352
81560
0018M

Background and Evidence Summary

Immune cell function assays measure T-cell or peripheral blood lymphocyte responses to stimulation (for example, intracellular ATP production, proliferation, or CD154 expression) to estimate cell-mediated immunity. Assays include ImmuKnow (measuring CD4 T-cell ATP after mitogenic stimulation), Pleximmune (measuring donor-induced CD154+ T-cytotoxic memory cells reported as a rejection risk score), iQue (multiplexed identification and functional characterization of immune cells), and various laboratory-developed tests. Professional society guidance is limited; notably, the International Society for Heart and Lung Transplantation (ISHLT) issued a Class III recommendation that the use of the ImmuKnow assay cannot be recommended for rejection monitoring in adult and pediatric heart transplant recipients.

Evidence Item	Key Findings
ImmuKnow pooled specificity/sensitivity (meta-analysis)	Meta-analyses report relatively high specificity (~0.75) but low sensitivity (~0.43) with significant heterogeneity across studies.
ImmuKnow for infection prediction (Wang et al., 2014)	Meta-analysis: pooled sensitivity 0.51 and specificity 0.75 for infection; for acute rejection reported DOR 13.81 with sensitivity 0.51 and specificity 0.90 in some analyses; authors did not support routine use for prediction/monitoring in renal transplant.
Pleximmune pediatric performance (Ashokkumar et al., 2017)	Training/validation in children: sensitivity ~84% and specificity ~80–81% for predicting acute cellular rejection using CD154+ T‑cytotoxic memory cell immunoreactivity index.
ImmuKnow clinical studies (various centers)	Multiple observational studies report lower ImmuKnow ATP levels associated with infection in transplant recipients; results vary by study and population (lung, pediatric liver, heart) with mixed predictive utility.
Randomized trial adjusting immunosuppression (Ravaioli et al., 2015)	In a randomized trial using ImmuKnow-guided tacrolimus adjustments, investigators reported improved survival and infection rates in the immune‑function‑guided arm versus control when dosing changes were made at specified ATP thresholds.
Regulatory / FDA status	ImmuKnow cleared by FDA (510(k)) in 2002; Pleximmune approved via HDE in 2014 for pediatric liver and small bowel transplant rejection risk prediction within 60 days.
Applicable procedure codes	CPT/HCPCS codes referenced for these assays include 86352, 81560, and 0018M (procedural coding for immune cell function and Pleximmune/Pleximark tests).

Thresholds

ImmuKnow assay categories (population-based)Strong ≥525 ng/mL; Moderate 226–524 ng/mL; Low ≤225 ng/mL

Kowalski immunological targetIntersection at 280 ng/mL ATP

Ravaioli immunosuppression adjustment thresholdsReduce tacrolimus 25% if ImmuKnow <130 ng/mL; increase tacrolimus 25% if >450 ng/mL

Xue diagnostic cut-off for infant infectionCylex ATP cut-off 152 ng/mL

Additional study cutoff notedKowalski example values: 25 ng/mL associated with infection risk; 700 ng/mL associated with rejection risk

OpenPayer

Immune Cell Function Assay Comm Bc Ma Dsnp G2098

Coverage Summary

Medical Necessity / Coverage Criteria

Coding

Provider Actions & Billing Impact

Background and Evidence Summary

Definitions

Revision History