HLA Testing Services

Disease Associations

The human leukocyte antigen (HLA) system is the body’s major histocompatibility complex that includes hundreds of genes located on chromosome 6 that encode for proteins critical for the immune system. Historically, these proteins are called antigens because of their critical role in tissue rejection by the host in organ transplantations. Although HLA typing is largely used to match organ donors and recipients, studies have found strong correlations between certain HLA types and the specific diseases described here. HLA typing is used as a screening tool when the rest of a patient's clinical picture is otherwise apparent.

Clinical Utility:

  • Celiac Disease – HLA-DQ2/DQ8/DQA1*05

    Celiac Disease (CD) is a multifactorial disorder in which specific HLA-DQA1 and HLA-DQB1 alleles represent the major genetic predisposition. HLA typing does not have an absolute diagnostic value but allows for assessment of the CD relative risk. This means a positive test is indicative of genetic susceptibility but does not necessarily mean disease development. A negative test has a more significant value because gluten intolerance rarely occurs in the absence of specific HLA predisposing alleles.

    Approximately 90% of Celiac Disease patients present DQA1*05 and DQB1*02(DQ2.5); 5-10% carry DQA1*03 and DQB1*0302 (DQ8); about 5% of patients present DQ2.x molecules, encoded by the DQB1*02 at-risk allele in absence of the DQA1*05; and very rarely, celiac patients carry different DQ molecules (DQX.x). The close association is because these disease-associated HLA-DQ molecules expressed on antigen-presenting cells specifically bind gluten-derived peptides that are modified by the enzyme tTG and present them to intestinal CD4+ T cells. The resulting T cell response leads to the production of auto-antibodies directed against tTG and to the secretion of pro-inflammatory cytokines (mainly TNF-α and IFN-γ) with consequent mucosa atrophy and clinical manifestations.

    The American Gastroenterological Association (AGA) Institute recommends testing for celiac disease in symptomatic individuals who are at particularly high risk. These include those with unexplained iron deficiency anemia, a premature onset of osteoporosis, Down syndrome, unexplained elevations in liver transaminase levels, primary biliary cirrhosis, and autoimmune hepatitis. Situations in which testing for celiac disease should be selectively considered during the medical evaluation, especially if symptoms that could be the result of celiac disease are present, include type 1 diabetes mellitus, autoimmune thyroid disease, Sjögren's syndrome, unexplained recurrent fetal loss, unexplained delayed puberty, selective IgA deficiency, irritable bowel syndrome, Turner's syndrome, peripheral neuropathy, cerebellar ataxia, and recurrent migraine, as well as children with short stature and first- and second-degree relatives of patients with celiac disease.

  • Rheumatoid Arthritis – HLA-DRB1*04:01/04:04

    About 1% of the world's population has rheumatoid arthritis, women three times as often as men. Onset is most frequent between the ages of 40 and 50, but people of any age can be affected. In addition, individuals with the HLA-DR1 or HLA-DR4 types have an increased risk for developing the disorder.

    Rheumatoid arthritis is a form of autoimmunity, the causes of which are still not completely known. It is strongly associated with the inherited tissue type Major histocompatibility complex (MHC) antigen HLA-DR4 (most specifically DRB1*04:01 and 04:04), hence family history is an important risk factor.

  • Narcolepsy – HLA-DRB1*15:01, HLA-DQB1*06:02

    Narcolepsy – HLA-DRB1*15:01, HLA-DQB1*06:02: One of the most important predisposing genetic factors is the HLA-DQB1*06:02 allele on the DRB1*15:01 – DQA1*01:02 – DQB1*06:02 haplotype. Between 85 and 95% of narcolepsy patients with cataplexy carry this haplotype. Persons homozygous for HLA-DQB1*06:02 carry a greater risk than heterozygous persons, though persons heterozygous for HLA-DQB1*03:01 and HLA-DQB1*06:02 are also at increased risk. HLA-DQB1*05:01 and DQB1*06:01 are thought to be protective for narcolepsy. HLA-DQB1*06:02 has a larger P4 pocket which would facilitate binding of larger hydrophobic residues compared to HLA-DQB1*06:01; this may help explain the opposite effects these two allele have on narcolepsy susceptibility.

    The genetic risk of developing narcolepsy is not fully explained by HLA-DQB1*06:02 as there are many patients with narcolepsy who do not carry HLA-DQB1*06:02, pointing to the possibility of non-HLA gene involvement. Candidate genes include the different hypocretin system genes, though initial studies have not shown an association and TNFα gene polymorphisms.

    Genetic testing for narcolepsy, particularly HLA-DQB1*06:02 typing, is useful as an aid to diagnosis in patients with cataplexy. But, the association is not specific as there are many narcolepsy patients with HLA-DQB1*06:02 and many HLA-DQB1*06:02 persons who do not have narcolepsy.

  • Ankylosing Spondylitis – HLA-B27

    Ankylosing spondylitis belongs to a group of spondyloarthropathies with a strong genetic predisposition. While considerable ethnic and geographic variation exists in the prevalence of AS, the strong familial associations of this disease, particularly among patients positive for HLA-B27, have implicated a role for an immunogenetic abnormality in the pathogenesis. Greater than 90% of patients with AS are HLA-B27 positive compared to 5-10% of the general population.

    The fact that approximately 90% of AS patients express the HLA-B27 genotype, a strong genetic association is suggested. Variations of the HLA-B gene increase the risk of developing AS, although it is not a diagnostic test. Those with the HLA-B27 variant are at a higher risk than the general population of developing the disorder. HLA-B27, demonstrated in a laboratory test, occasionally helps with diagnosis but in itself is not diagnostic of AS in a person with back pain. It is important to note that HLA-B27 is a perfectly normal gene found in 8% of the Caucasian population. Generally speaking, no more than 2% of people born with this gene will eventually get spondylitis. The risk factors that predispose a person to AS include:

    - Testing positive for the HLA-B27 marker
    - A family history of AS
    - Frequent gastrointestinal infections

    The severity of AS varies greatly from person to person, and not everyone will experience the most serious complications or develop spinal fusion. Some will experience only intermittent back pain and discomfort, but others will suffer severe pain and stiffness over multiple areas of the body for long periods of time. AS can be profoundly debilitating.

  • Behcet's Disease – HLA-B51

    Behcet's disease (BD) is a rare immune-mediated systemic vasculitis that often presents with mucous membrane ulceration and ocular problems. It is a triple-symptom complex of recurrent oral aphthous ulcers, genital ulcers, and uveitis. Behcet's disease is considered more prevalent in the areas surrounding the old silk trading routes in the Middle East and in Central Asia; thus it is sometimes known as Silk Road Disease. However, BD is not restricted to people from these regions. A large number of studies show a linkage between the disease and HLA-B51. Although it is strongly associated with Behcet's disease, HLA-B51 testing is not used exclusively for its diagnosis.

  • Birdshot Chorioretinopathy – HLA-A29

    Birdshot chorioretinopathy is a rare form of posterior uveitis and accounts for 1-3% of uveitis cases in general. Thought to be an autoimmune disease, it affects typically middle aged or elderly Caucasians.

    Birdshot chorioretinopathy has strong association with the Human leukocyte antigen haplotype (HLA)-A29, which is the strongest association between a disease and HLA class I documented (85 to 97.5% of patients are HLA-A29 positive). This indicates a role for T-lymphocytes in the pathogenesis. Birdshot chorioretinopathy is associated with IL-17, a hallmark cytokine of TH17 cells that play an important role in autoimmunity. HLA-A29 is less prevalent in Asia and no birdshot chorioretinopathy cases have been reported in Asia.

    When birdshot chorioretinopathy is suspected, patients are usually tested to determine if they are HLA-A29 positive. However, HLA-A29 testing is not considered necessary for definitive diagnosis because HLA-A29 is also common in the general healthy population (7%). Additional (genetic or environmental) or unknown factors may be associated with HLA-A29 in the pathogenesis.



PCR-SSO: Reverse SSO hybridization is used to determine HLA-A, B, C, DR and DQ locus types at an intermediate level of resolution.

SBT: SBT provides the highest resolution HLA typing for HLA-A, -B, -C, -DR, -DQ and -DP locus alleles.

Specimen Requirements:

One 5-mL EDTA (purple top) tube or 4 buccal swabs
Other anticoagulants accepted.

Shipping Requirements:

Samples are accepted Monday through Friday. Overnight shipments should be sent Monday through Thursday. Please send samples, at room temperature, along with the completed test requisition to:

Kashi Clinical Laboratories, Inc.
Attention: HLA Laboratory
10101 SW Barbur Blvd, Suite 200
Portland, OR 97219