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Human Leukocyte Antigen (HLA) testing

Indications: - determination of transplant compatibility - assessing risk of an adverse reaction to specific drugs (pharmacogenomics) - evaluations of disease associations - lymphoma [4] - use in vaccine trials - platelet transfusion support Epidemiology: - seems Hans Chinese & persons of Thai descent at risk for drug hypersensitivity Procedure: - currently, the majority of HLA typing is done by molecular methods using commercially available kits - probe-based hybridization methods - massively parallel sequencing - some laboratories can query single nucleotide variants associated with certain HLA alleles vs directly testing for the allele. === HLA typing for solid organ transplantation === - for deceased donors, molecular typing of class I & II HLA loci (HLA A, B, Bw4, Bw6, C, DR, DR51, DR52, DR53, DQA1, DQB1, & DPB1) must be reported [8] - for kidney, kidney-pancreas, pancreas, or pancreas islet candidates, molecular typing of a smaller subset of both class I & class II HLA loci (HLA A, B, Bw4, Bw6, & DR) must be reported before registering on the wait list [8] - a final crossmatch is required before any transplant involving a kidney - the crossmatch must identify all class I & class II antibodies using donor B-lymphocytes & must identify all class I anti-HLA antibodies using donor T-lymphocytes [8] - crossmatching is done in specialized histocompatibility laboratories - methods include complement-dependent cytotoxicity or flow cytometry === Hematopoietic stem cell transplantation === - high-resolution molecular typing of class I HLA loci (HLA A, B, C) & some class II HLA loci (HLA DRB1 & DPB1) is recommended for all individuals either receiving or donating an allogeneic hematopoietic stem cell transplantation [8] - typing of other class II HLA loci may also be useful - if umbilical cord blood is used as the source of hematopoietic stem cells, high-resolution molecular typing of all class I HLA loci (HLA A, B, C) & HLA-DRB1 is recommended - typing of DQB1 & DPB1 may also be useful === Pharmacogenetics === - specific HLA-B alleles associated with drug hypersensitivity reactions - HLA-B*5701 for abacavir sensitivity [8] - HLA-B*1502 (HLA-B75) (carbamazepine, phenytoin)* - HLA-B*5801 (allopurinol) * susceptibility to Stevens-Johnson syndrome & toxic epidermal necrolysis [6] === Disease associations === - Ankylosing Spondylitis Genotyping (HLA-B27) - Celiac disease: HLA-DQ2 &/or HLA-DQ8 present in nearly all patients - Dermatitis herpetiformis: - HLA-DQ2 (encoded by HLA-DQA1*05 7 HLA-DQB1*02) present in 90% - HLA-DQ8 (encoded by HLA-DQB1*03:02) present in ~5-10% - Narcolepsy: HLA-DQB1*06:02 genotyping [8] Pathology: - HLA antigens are the principle mediators involved in transplant rejection [7] Notes: - the human leukocyte antigen (HLA) genes are located on a genetic region of the short arm of chromosome 6 known as the major histocompatibility complex [5]

Specific

HLA B testing HLA-A type HLA-A+B type HLA-A+B+C type HLA-C type Human Leukocyte Antigen (HLA) Class I serotyping Human Leukocyte Antigen (HLA) Class II serotyping human leukocyte antigen (HLA) genotyping

General

hematology panel tissue typing

References

  1. Prescriber's Letter 15(2): 2008 Labs for HLA (Human Leukocyte Antigen) Testing Detail-Document#: 240211 (subscription needed) http://www.prescribersletter.com - Prescriber's Letter 16(1): 2009 Labs for HLA (Human Leukocyte Antigen) Testing Detail-Document#: 250109 (subscription needed) http://www.prescribersletter.com
  2. Khanna D et al 2012 American College of Rheumatology guidelines for management of gout. Part 1: Systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia Arthritis Care & Research, 64(10):1431-1446, October 2012 PMID: 23024028 http://onlinelibrary.wiley.com/doi/10.1002/acr.21772/abstract
  3. Labs that perform HLA testing American Red Cross, Philadelphia, PA (215) 451-4131 - Blood Systems Laboratories Histocompatibility Testing Services Tempe, AZ (866) 342-4275 http://www.bloodsystemslaboratories.org - Calgary Laboratory Services-Tissue Typing Laboratory Calgary, Alberta (Canada) (403) 770-3652 - City of Hope National Medical Center Histocompatibility Laboratory, Duarte, CA (626) 256-8621 - The Histogenetics Laboratory, Inc., Ossining, NY (914) 762-0300 http://www.histogenetics.com - Kashi Clinical Laboratories, Beaverton, OR (888) 732-4018 - Laboratory Corporation of America Holdings, Burlington, NC (800) 533-1037 http://www.labcorp.com - METIC Immunogenetics Consultants, Inc., Los Angeles, CA (323) 441-1111 http://www.metic.com - Quest Diagnostics Nichols Institute Chantilly, VA (800) 336-3718 http://www.questdiagnostics.com - Specialty Laboratories, Valencia, CA (800) 421-4449 http://www.specialtylabs.com - The Toronto Hospital Toronto, ON (Canada) (416) 340-4995 - Vancouver Acute, Laboratory Reception, Vancouver, BC (Canada) (604) 875-4111 http://www.vch.ca
  4. Deprecated Reference
  5. Moyer AM, Gandhi MJ. Human Leukocyte Antigen (HLA) Testing in Pharmacogenomics. Methods Mol Biol. 2022;2547:21-45. PMID: 36068459
  6. Karnes JH, Rettie AE, Somogyi AA et al Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update. Clin Pharmacol Ther. 2021 Feb;109(2):302-309. PMID: 32779747 PMCID: PMC7831382 Free PMC article. Review.
  7. Kamal S, Kerndt CC, Lappin SL Genetics, Histocompatibility Antigen National Library of Medicine, NCBI Bookshelf: StatPearls https://www.ncbi.nlm.nih.gov/books/NBK541023/
  8. ARUP Laboratories HLA Testing https://arupconsult.com/content/hla-testing