CPT 81375 HLA Class II Reimbursement | OpenPayer

Summary & Overview

CPT 81375: HLA Class II Low/Intermediate-Resolution Molecular Typing

CPT code 81375 represents a laboratory test for low- or intermediate-resolution molecular typing of human leukocyte antigen (HLA) Class II loci, including HLA–DRB1/3/4/5 and HLA–DQB1. This code identifies the technical component of molecular HLA testing used in transplant compatibility assessment, immunogenetics research, and certain diagnostic contexts where class II HLA determination is clinically relevant. Nationally, HLA typing remains critical for organ and stem cell transplantation programs and for select autoimmune disease evaluations, making accurate coding important for clinical workflows and payer reimbursement.

Key payers referenced in this analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find a concise overview of clinical context, typical sites of service, and the types of insights commonly included in billing-code publications: utilization benchmarks, coding guidance and common modifiers, and relevant policy or coverage considerations. Where specific payer policy details or taxonomies are not available in the input, the summary notes that data is not available.

This publication provides clinicians, billing staff, and policy analysts with a clear description of what CPT code 81375 covers, where the service is typically performed, and what to expect in terms of the content areas usually reviewed when evaluating HLA molecular testing codes.

AetnaBlue Cross Blue ShieldCigna HealthUnitedHealthcareMedicareCPT 81375HLA typingmolecular diagnosticslaboratory servicestransplant compatibilityclass II HLAtechnical componentimmunogenetics

Billing Code Overview

CPT code 81375 describes a laboratory technical procedure for low- or intermediate-resolution molecular assessment of human leukocyte antigen (HLA) genes for all listed Class II loci. The test specifically includes Class II loci HLA–DRB1/3/4/5 and HLA–DQB1 and is performed using molecular techniques.

Service type: Laboratory — molecular HLA typing (technical component)

Typical site of service: Clinical laboratory or hospital laboratory

Clinical & Coding Specifications

Clinical Context

A 42-year-old patient undergoing evaluation for kidney transplantation is referred for HLA Class II typing to assess compatibility with a potential living donor. The ordering clinician is a transplant nephrologist coordinating pre-transplant immunogenetic workup. The patient presents to an outpatient phlebotomy clinic where a blood sample is collected and sent to a molecular diagnostics laboratory. In the lab, a molecular technologist performs low- or intermediate-resolution HLA Class II typing using sequence-specific oligonucleotide (SSO) or sequence-specific primer (SSP) methods to determine HLA–DRB1/3/4/5 and HLA–DQB1 alleles. Results are reported to the transplant team and entered into the transplant registry for donor-recipient matching and immunologic risk assessment. Typical workflow steps include order entry, specimen collection, accessioning, DNA extraction, PCR-based molecular typing, result interpretation by the lab analyst, and transmission of a coded report to the transplant program and electronic health record. Typical site of service is an outpatient molecular diagnostic laboratory or hospital-based immunogenetics laboratory with coordination from the transplant clinic.

Coding Specifications

Modifier	Description	When to Use
`26`	Professional component	Use when only the professional interpretation/reporting component of the test is billed separately from the technical processing.

CPT 81381: HLA High-Resolution Test for One Class I Allele

CPT-81378-HLA-HIGH-RESOLUTION-MOLECULAR-TYPING-CLASS-I-II-DRB1

CPT 81378: High-Resolution HLA Class I and II Molecular Typing

CPT-81376-HLA-CLASS-II-TYPING-LOW-INTERMEDIATE-RESOLUTION-TECHNICAL

CPT 81376: HLA Class II Typing, Low/Intermediate-Resolution Technical

CPT-81379-HLA-CLASS-I-HIGH-RESOLUTION-TYPING

CPT 81379: High-Resolution HLA Class I Typing

CPT-81373-HLA-CLASS-I-LOW-INTERMEDIATE-RESOLUTION

CPT 81373: HLA Class I Low/Intermediate Resolution Molecular Test

CPT-81382-HLA-HIGH-RESOLUTION-CLASS-II-TECHNICAL

CPT 81382: HLA High-Resolution Molecular Typing, One Class II Locus

CPT-81377-HLA-CLASS-II-ALLELE-GROUP-TYPING-LOW-INTERMEDIATE-RESOLUTION

CPT 81377: HLA Class II Allele Group Typing, Low/Intermediate Resolution

CPT-81372-HLA-CLASS-I-LOW-INTERMEDIATE-RESOLUTION-TYPING

CPT 81372: HLA Class I Low/Intermediate-Resolution Molecular Typing

CPT-81383-HIGH-RESOLUTION-HLA-CLASS-II-ALLELE-TESTING

CPT 81383: High-Resolution HLA Class II Allele Technical Test

CPT-81370-HLA-CLASS-I-II-LOW-INTERMEDIATE-RESOLUTION-TESTING

CPT 81370: HLA Class I and II Low/Intermediate-Resolution Molecular Typing

Showing 1–10 of 13

Taxonomy Code	Specialty	Notes
2080P0800X	Clinical Molecular Genetics Laboratory	Laboratory specialty performing molecular HLA typing and reporting.
208000000X	Clinical Laboratory	General clinical lab providing technical processing and testing.
207RC0000X	Transplant Surgery	Ordering specialty coordinating transplant compatibility testing.
207LP2900X	Nephrology	Ordering specialty for kidney transplant candidates initiating HLA typing.
207L00000X	Immunology	Specialty involved in immunogenetics interpretation and transplant immunology.

Related Diagnoses

ICD-10 Code	Description	Clinical Relevance
`Z94.0`	Kidney transplant status	Used for recipients requiring HLA Class II typing for donor match evaluation or post-transplant monitoring.
`Z48.21`	Encounter for aftercare following kidney transplant	Relevant when monitoring or reassessing HLA compatibility or for post-transplant immunologic workup.
`Z21`	Asymptomatic human immunodeficiency virus [HIV] infection status	Relevant in transplant assessment where HLA typing may be part of pre-transplant workup for complex immunologic status.
`T86.10`	Unspecified complication of kidney transplant	HLA typing may be used in evaluation of graft dysfunction when antibody-mediated processes are suspected.
`Z77.9`	Contact with and (suspected) exposure to communicable disease, unspecified	Included when pre-transplant infectious risk assessment coincides with immunogenetic testing.

Related CPT Codes

CPT Code	Description	Relationship to This Procedure
`81376`	HLA class II high-resolution typing, DRB1/3/4/5, DQB1 by molecular methods	Often performed when high-resolution allele-level typing is required after low/intermediate resolution `81375` for donor selection or desensitization planning.
`81479`	Unlisted molecular pathology procedure	Used for specialized or emerging HLA molecular assays not captured by existing codes when required.
`86850`	Blood typing; ABO	Performed as part of pre-transplant immunohematology screening alongside HLA typing.
`86308`	HLA antibody identification, single antigen bead	Complementary testing to HLA typing to assess recipient sensitization and antibody specificity in transplant evaluation.
`88240`	DNA probe; other specified probe	Ancillary molecular methods occasionally used in comprehensive immunogenetic workups in specialized labs.

OpenPayer