Immune Cell Function Assay
Customize your policy alerts
Sign up for all blue cross blue shield - tennessee policy alerts
Know when blue cross blue shield - tennessee releases new policies or updates existing guidance.
Monitor payer policy activity
This policy governs coverage and limitations for immune cell function assays (tests measuring peripheral blood lymphocyte responses such as intracellular ATP, proliferation, and related assays) for Blue Cross Blue Shield of Tennessee members. It applies to clinical use in diagnosis and monitoring across indications including transplant and primary immunodeficiency.
No material clinical or coverage changes in this revision.
Coverage Determinations
Evidence and guideline context
Summary of guideline and regulatory context relevant to immune cell function assays:
Regulatory Status, Cutoffs, and Definitions
| ImmuKnow | Immune Cell Function Assay (Cylex/Viracor) — FDA 510(k) clearance April 2002; subsequent 510(k) device modification clearance 2010 (no change in indications) |
| Pleximmune | Pleximmune™ (Plexision) — FDA approval via Humanitarian Device Exemption August 2014; intended to predict risk of transplant rejection within 60 days in pediatric liver and small bowel transplant patients |
Provider Requirements and Actions
Prior Authorization Required
Prior Authorization Likely Required. Requests for immune cell function assays are subject to review and may require prior authorization; services for indications lacking evidence are at high risk for denial.
- Affected requests: immune cell function assays (e.g., ImmuKnow®, Pleximmune™, and laboratory-developed tests).
- Denial risk high for indications without published evidence of benefit (see list in Indications and/or Limitations).
Document Clinical Indication and Prior Testing
Requests for immune cell function assays must include documentation of the clinical indication and relevant prior testing. Providers should document why testing is clinically necessary and include results of inexpensive screening tests performed prior to advanced assays.
- Document the specific clinical indication.
- Attach prior screening test results (e.g., flow cytometry enumerating CD4/CD8/T cells, serum immunoglobulin levels, lymphocyte proliferation to mitogens).
- Include prior treatment history and how results will change management.
Stepwise Clinical Approach Recommended
Stepwise Clinical Approach Advised. Providers should perform inexpensive, validated screening tests before pursuing advanced immune cell function assays. Abnormal screening results may justify more sophisticated testing.
- Recommended initial screening: flow cytometry to enumerate CD4, CD8, and NK cells; serum immunoglobulin levels.
- Use mitogen/antigen stimulation testing only when screening tests are abnormal or clinical algorithms (e.g., newborn screening TREC results) indicate further evaluation.
- Avoid advanced or costly assays as first-line testing.
Step Therapy
No Step Therapy Requirements Specified. There are no formal step therapy or prior-treatment sequencing mandates beyond the general expectation to perform standard screening tests first.
- No defined step therapy program for immune cell function assays in this policy.
- Clinical judgment expected to follow guideline-recommended screening and diagnostic pathways.
Denial Conditions for Unproven Indications
Denial Risk for Unproven Indications. Requests will be denied when immune cell function assays are used for indications lacking published evidence of benefit (for example: prediction or management of transplant rejection, pre-transplant risk identification, management of hematopoietic stem cell transplantation, routine management of immunodeficiency including HIV/SCID, prediction of infection risk in autoimmune diseases, testing for urticaria, or Lyme disease testing such as iSpot Lyme).
- Examples of noncovered uses: management of solid organ transplant rejection, prediction of rejection risk pre-transplant, management of autologous/allogeneic HSCT, routine HIV/SCID management, infection risk prediction in RA/MS/lupus nephritis, urticaria testing, Lyme disease diagnosis (iSpot).
Consult Government Coverage Determinations
Follow Applicable Government Policy. If a conflict exists between this policy and an applicable government policy (LCD/NCD or state Medicaid), the government policy will govern the determination. FDA clearance or LDT validation does not guarantee coverage.
- Check current Medicare LCDs/NCDs and applicable state Medicaid rules when requesting coverage determinations.
- Note: FDA clearance (e.g., ImmuKnow®, Pleximmune™) or CLIA LDT status does not ensure coverage; government determinations override this policy.
Clinical Background
Primary immunodeficiency disorders are rare conditions in which components of the immune system are absent or dysfunctional. T-cell defects in particular can produce combined immunodeficiency phenotypes and are clinically important because they impair cell-mediated immunity (CMI). In vitro T-cell function testing—measuring responses to mitogens, antigens, or allogeneic stimulation by methods such as proliferation assays or ATP-based assays—has been studied as a way to identify T-cell dysfunction, guide evaluation of recurrent or severe infections, and inform transplant-related immune monitoring; however, the policy emphasizes variable performance and insufficient evidence of benefit for routine clinical use.
Key Terms and Test Names
Policy Revision History
Policy effective date: 7/1/2023 — policy adopted based on Avalon policy recommendation.
OpenPayer is powered by Trek Health's payer performance platform. Trek continuously ingests, validates, and normalizes Transparency in Coverage data alongside payer policies and other commercial payer data to create a structured payer intelligence foundation. OpenPayer uses this foundation to deliver personalized search results, dynamically generated policy pages, and tailored policy monitoring based on each user's payers, specialties, billing codes, and areas of interest. The same intelligence powers broader payer performance workflows, including reimbursement benchmarking, contract evaluation, payer negotiations, and financial decision-making.