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Official Description

HLA Class II typing, low resolution (eg, antigen equivalents); HLA-DRB1/3/4/5 and -DQB1

© Copyright 2025 American Medical Association. All rights reserved.

Common Language Description

The human leukocyte antigen (HLA) system is a critical component of the major histocompatibility complex (MHC), which plays a vital role in the immune system's ability to recognize self from non-self. This system is essential for the identification of specific characteristics of an individual's cells and tissues, enabling the body to defend against foreign substances, including microorganisms and non-self cells. The HLA system is located on the short arm of chromosome 6 and is divided into two classes: Class I and Class II. HLA Class II is particularly important as it consists of five loci—DR, DQ, DP, DM, and DO—with DR, DQ, and DP being the most significant for immune response. Each locus contains various variants known as alleles, which are designated by the locus name followed by an asterisk (*) and a series of digits that provide specific information about the allele. For instance, DRB1*15 indicates a specific allele within the DRB1 locus. HLA Class II antigens are crucial for initiating general immune responses. The process of HLA typing involves extracting DNA from nucleated cells, which requires cell lysis and protein digestion. Most molecular methods for HLA typing utilize polymerase chain reaction (PCR) techniques, specifically PCR sequence specific priming (SSP) for low resolution typing. This method employs a panel of primer pairs to amplify groups of alleles, allowing for the identification of antigen equivalents. The CPT® Code 81375 is used when low resolution testing for all five HLA Class II loci—DRB1, DRB3, DRB4, DRB5, and DQB1—is performed. In contrast, CPT® Code 81376 is designated for low resolution testing of a single HLA Class II locus, while CPT® Code 81377 is used for testing a single HLA Class II antigen equivalent.

© Copyright 2025 Coding Ahead. All rights reserved.

1. Indications

The HLA Class II typing procedure is indicated for various clinical scenarios where understanding an individual's HLA profile is essential. These indications include:

  • Transplant Compatibility: HLA typing is crucial for determining compatibility between organ donors and recipients to minimize the risk of transplant rejection.
  • Autoimmune Disorders: It is used in the diagnosis and management of autoimmune diseases, where specific HLA types may be associated with increased susceptibility.
  • Bone Marrow Transplantation: HLA typing is performed to ensure donor-recipient matching in hematopoietic stem cell transplants.
  • Pharmacogenomics: Certain HLA types are linked to adverse drug reactions, making HLA typing important for personalized medicine approaches.
  • Infectious Disease Susceptibility: HLA typing can help assess an individual's susceptibility to certain infections based on their immune response capabilities.

2. Procedure

The procedure for HLA Class II typing using CPT® Code 81375 involves several key steps:

  • Sample Collection: A sample of nucleated cells is collected, typically from blood or bone marrow, to obtain the necessary DNA for testing.
  • Cell Lysis and Protein Digestion: The collected cells undergo a process of lysis, where the cell membranes are broken down, followed by protein digestion to prepare the DNA for extraction.
  • DNA Extraction: The DNA is extracted from the lysed cells, isolating it for further analysis.
  • Polymerase Chain Reaction (PCR): The extracted DNA is subjected to PCR, a technique that amplifies specific DNA sequences associated with the HLA Class II loci.
  • Sequence Specific Priming (SSP): PCR SSP is employed, utilizing a panel of primer pairs designed to amplify groups of alleles corresponding to the HLA Class II loci, specifically targeting DRB1, DRB3, DRB4, DRB5, and DQB1.
  • Analysis of Results: The amplified DNA is analyzed to identify the specific HLA Class II antigen equivalents present, providing a low resolution typing result.

3. Post-Procedure

After the HLA Class II typing procedure, the results are typically reviewed and interpreted by a qualified healthcare professional. The expected recovery from the sample collection is generally minimal, with patients advised to follow any specific post-collection care instructions provided by the healthcare provider. The results of the HLA typing can take several days to process, and patients may need to discuss the implications of their HLA type with their physician, especially in the context of transplantation or disease susceptibility. It is important to ensure that all documentation related to the procedure and results is accurately maintained for compliance and future reference.

Short Descr HLA II TYPING AG EQUIV LR
Medium Descr HLA II LOW RESOLUTION HLA-DRB1/3/4/5 AND -DQB1
Long Descr HLA Class II typing, low resolution (eg, antigen equivalents); HLA-DRB1/3/4/5 and -DQB1
Status Code Statutory Exclusion (from MPFS, may be paid under other methodologies)
Global Days XXX - Global Concept Does Not Apply
PC/TC Indicator (26, TC) 9 - Not Applicable
Multiple Procedures (51) 9 - Concept does not apply.
Bilateral Surgery (50) 9 - Concept does not apply.
Physician Supervisions 09 - Concept does not apply.
Assistant Surgeon (80, 82) 9 - Concept does not apply.
Co-Surgeons (62) 9 - Concept does not apply.
Team Surgery (66) 9 - Concept does not apply.
Diagnostic Imaging Family 99 - Concept Does Not Apply
CLIA Waived (QW) No
APC Status Indicator Service Paid under Fee Schedule or Payment System other than OPPS
Type of Service (TOS) 5 - Diagnostic Laboratory
Berenson-Eggers TOS (BETOS) T1H - Lab tests - other (non-Medicare fee schedule)
MUE 1
CCS Clinical Classification 234 - Pathology
90 Reference (outside) laboratory: when laboratory procedures are performed by a party other than the treating or reporting physician or other qualified health care professional, the procedure may be identified by adding modifier 90 to the usual procedure number.
GA Waiver of liability statement issued as required by payer policy, individual case
59 Distinct procedural service: under certain circumstances, it may be necessary to indicate that a procedure or service was distinct or independent from other non-e/m services performed on the same day. modifier 59 is used to identify procedures/services, other than e/m services, that are not normally reported together, but are appropriate under the circumstances. documentation must support a different session, different procedure or surgery, different site or organ system, separate incision/excision, separate lesion, or separate injury (or area of injury in extensive injuries) not ordinarily encountered or performed on the same day by the same individual. however, when another already established modifier is appropriate it should be used rather than modifier 59. only if no more descriptive modifier is available, and the use of modifier 59 best explains the circumstances, should modifier 59 be used. note: modifier 59 should not be appended to an e/m service. to report a separate and distinct e/m service with a non-e/m service performed on the same date, see modifier 25.
XU Unusual non-overlapping service, the use of a service that is distinct because it does not overlap usual components of the main service
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2012-01-01 Added Added
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