HLA-B 5701 Genotype, Abacavir Hypersensitivity, Blood
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Assisting a physician in developing a therapeutic management strategy for HIV-infected patients
Predicting likelihood of hypersensitivity reactions to abacavir in HIV-infected patients, based on the presence of the human leukocyte antigen HLA-B*5701 allele
Aiding in differentiating between true hypersensitivity to abacavir versus other underlying causes (eg, concomitant infection, reaction to other drugs, or inflammatory disease)
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
See Abacavir Hypersensitivity Testing and Initial Patient Management Algorithm in Special Instructions
Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test
Qualitative Allele-Specific Real-Time Polymerase Chain Reaction (PCR)
(PCR is utilized pursuant to a license agreement with Roche Molecular Systems, Inc.)
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
HLA-B 5701 Genotype, Abacavir, B
Specimen Type Describes the specimen type needed for testing
Whole Blood EDTA
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Multiple whole blood EDTA genotype tests can be performed on a single specimen. See Multiple Whole Blood EDTA Genotype Tests in Special Instructions for a list of tests that can be ordered together.
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions: Send specimen in original tube.
Additional Information: Patients who had a heterologous blood transfusion within the preceding 45 days (6 weeks), or who have received an allogeneic bone marrow transplant, can have false genetic test results as human DNA present in the blood may be a mixture of patient and donor DNA. For these patients, a saliva specimen (rather than blood) should be submitted (HL57O/60347 HLA-B 5701 Genotype, Abacavir Hypersensitivity, Saliva).
Forms: New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (Supply T576) is available in Special Instructions.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
|Whole Blood EDTA||Ambient (preferred)|
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Human leukocyte antigen (HLA) genes are localized to chromosome 6. These genes affect the response of the immune system to infection by viruses and bacteria, and direct antibody production against foreign substances or antigens. HLA-B is a subclass of the HLA system. Based on DNA sequence variation, over 2,400 different versions of the gene, that codes for the HLA-B antigen, have been identified in the human population. The HLA-B*57 family consists of at least 57 closely related genes. Around 5% to 8% of the Western European and Hispanic populations express 57-like antigens, so this represents a common HLA genotype. This genotype is less frequent in other ethnic groups, and is found in <2% of people of African origin.
The products of the 5701 gene family members have been associated with hypersensitivity to abacavir, a highly effective nucleoside analog reverse-transcriptase inhibitor used to treat HIV infection and AIDS. The HLA-B*5701 genotype has been shown to be highly predictive of abacavir hypersensitivity in Western European populations. Hypersensitivity reactions, which generally occur during the first 6 weeks of treatment, are often nonspecific and include skin rashes, gastrointestinal symptoms (eg, nausea, vomiting, diarrhea, and abdominal pain), and respiratory symptoms. Fatalities have been reported with abacavir. Prospectively testing for the HLA-B*5701 genotype and excluding HLA-B*5701-positive individuals from treatment with abacavir decreases the incidence of abacavir hypersensitivity.
The HLA-B*5701 allele is also associated with flucloxacillin-induced liver injury in a single study. Individuals who have at least 1 copy of the HLA-B*5701 allele have an 80-fold increased risk of serious liver injury when treated with flucloxacillin. The actual liver injury is thought to be caused by a polymorphism in the neighboring HCP5 gene that is located in the major histocompatibility gene cluster and is inherited tightly linked to the HLA-B*5701 allele.
See Abacavir Hypersensitivity Testing and Initial Patient Management Algorithm in Special Instructions.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Positivity for human leukocyte antigen allele HLA-B*5701 confers high risk for hypersensitivity to abacavir.
See Abacavir Hypersensitivity Testing and Initial Patient Management Algorithm in Special Instructions.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Interpretation is more critical when there is a clinical history of, or when the physician suspects, an abacavir hypersensitivity reaction. Although the negative predictive value of the test is high, a negative HLA-B*5701 result does not preclude the development of an allergic response to abacavir and cannot substitute for clinical vigilance whenever abacavir therapy is administered. As symptoms of abacavir hypersensitivity are often nonspecific and can imitate other conditions commonly seen in HIV patients on antiviral therapy, the phenotypic diagnosis of abacavir hypersensitivity can be quite challenging. There is significant variability among patients identified as hypersensitive to abacavir.
Newly discovered rare HLA-B alleles are being reported in individuals and may result from gene conversion activities between HLA gene loci. This assay also detects closely related, but rare, alleles including *5708, *5710, *5713, *5714, *5715, *5716, and *5514. There are, as yet, no data indicating whether these subtypes are associated with hypersensitivity.
Not all individuals who are positive for HLA-B*5701 will have a hypersensitivity reaction.
Allogeneic bone marrow or stem cell transplants will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 for instructions.
Heterologous transfusions of blood that has not been depleted of leukocytes may interfere with testing for up to 4 to 6 weeks. DNA obtained from white cells may not provide useful information for patients who received a recent transfusion of blood that was not leukocyte-reduced. Wait 4 to 6 weeks until transfused cells have left the patient's circulation before drawing the patient's blood specimen for genotype testing.
Sensitivity of this assay for detecting human leukocyte antigen HLA-B*5701 allele approaches 100% with specificity near 96%.(5)
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Mallal S, Nolan D, C Witt, et al: Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 2002;359:727-732
2. Faruki H, Heine U, Brown T, et al: HLA-B*5701 clinical testing: early experience in the United States. Pharmacogenet Genom 2007;17:857-860
3. Sun HY, Hung CC, Lin PH, et al: Incidence of abacavir hypersensitivity and its relationship with HLA-B*5701 in HIV-infected patients in Taiwan. J. Antimicrob Chemother 2007;60:599-604
4. Mallal S, Phillips E, Carosi G, et al: HLA-B*5701 screening for hypersensitivity to abacavir. N.Engl J Med 2008;358:568-579
5. Saag M, Balu R, Brachman P, et al: High sensitivity of HLA-B*5701 in whites and blacks in immunologically-confirmed cases of abacavir hypersensitivity. 4th IAS Conference on HIV Pathogenesis, Treatment, and Prevention. July 22-25, 2007. Sydney. Abstract WEAB305)
6. Daly AK, Donaldson PT, Bhatnagar P, et al: HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 2009;41:816-819
Method Description Describes how the test is performed and provides a method-specific reference
Genomic DNA is extracted from whole blood. Amplification for the HLA-B*5701 allele and an internal control gene is performed by real-time PCR in the presence of SYBR Green which fluoresces when bound to double-stranded DNA. A genotype is assigned based on the allele-specific SYBR Green fluorescent signals that are detected.(Hammond E, Mamotte C, Nolan D, Mallal S: HLA-B*5701 typing: evaluation of an allele-specific polymerase chain reaction melting assay. Tissue Antigens 2007 Jul;70:58-61)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Whole Blood: 2 weeks Extracted DNA: 2 months
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
81381-HLA Class I typing, high resolution (ie, alleles or allele groups); one allele or allele group (eg, B*57:01P), each
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
|Result ID||Reporting Name||LOINC Code|
|89346||HLA-B 5701 Result||42358-2|
|29315||HLA-B 5701 Interpretation||69047-9|
|29316||HLA-B 5701 Reviewed by||69047-9|