HLA-DQA1*05 Genetic Testing for Crohn's Disease Biologics

If you have ever lost response to a biologic and wondered why it stopped working, a genetic variant called HLA-DQA1*05 may hold part of the answer. Carried by roughly 40 percent of people of European descent, this gene variant nearly doubles the risk of forming anti-drug antibodies against infliximab (Remicade) and adalimumab (Humira) in Crohn's disease (1). HLA-DQA1*05 testing is a pharmacogenomic blood test that can help you and your gastroenterologist choose the right biologic - and decide whether adding an immunomodulator is worth it - before treatment even begins.

This guide explains what the test measures, how the science has evolved through 2025, and what your results might mean for your treatment plan.

Key Takeaways

• HLA-DQA1*05 carriers face nearly double the risk of forming anti-drug antibodies to infliximab and adalimumab (hazard ratio 1.90, 95% CI 1.60 to 2.25) (1)
• In the PANTS study, immunogenicity reached 92% at one year for infliximab monotherapy carriers vs. only 10% for adalimumab combination therapy non-carriers (1)
• A 2025 study distinguished two subtypes: *05:01 shortens time to loss of response with infliximab, while *05:05 shortens it with adalimumab (2)
• The test does not predict response to vedolizumab (Entyvio), ustekinumab (Stelara), or other non-TNF biologics (2)
• Labcorp test 167680 is available in the US using a standard blood draw and next-generation sequencing (6)
• Results are most useful before starting anti-TNF therapy, when they can still shape the initial treatment plan

What Is HLA-DQA1*05 and Why Does It Matter for Crohn's Disease?

HLA-DQA1*05 is a common variant in the human leukocyte antigen (HLA) gene family - the same set of genes that helps your immune system distinguish your own proteins from foreign ones. In Crohn's disease patients starting anti-TNF biologics, this variant makes the immune system more likely to recognize infliximab or adalimumab as foreign and mount an antibody response against them (1). Those anti-drug antibodies (ADAs) can reduce circulating drug levels, cause loss of response, and ultimately force a switch to a different biologic.

A Quick Primer on HLA Genes and the Immune System

HLA genes encode proteins on the surface of your cells that present fragments of proteins to immune cells. When these proteins flag a molecule as foreign, the immune system attacks it. Normally this protects you from infections. But in the case of anti-TNF therapies, the immune system can mistakenly identify the biologic drug itself as a threat - especially in people carrying certain HLA variants. HLA-DQA1*05 is the most clinically significant of these variants for Crohn's patients on anti-TNF drugs.

The *05:01 and *05:05 Subtypes

Not all HLA-DQA1*05 carriers face the same risks. In recent IBD cohorts, approximately 22.5 percent carried the *05:01 subtype and 20.7 percent carried the *05:05 subtype (2, 5). As we will explore below, these two subtypes appear to affect infliximab and adalimumab differently - a distinction that emerged in 2025 research and has practical implications for which anti-TNF your gastroenterologist might recommend.

The Science: HLA-DQA1*05, Anti-Drug Antibodies, and Loss of Response

The connection between HLA-DQA1*05 and biologic failure has been built through progressively larger studies over the past several years. Understanding these findings can help you have a more informed conversation with your care team about treatment planning.

The PANTS Consortium Findings

The landmark PANTS (Personalised Anti-TNF Therapy in Crohn's disease) study followed 1,240 Crohn's patients starting infliximab or adalimumab across the United Kingdom (1). The results were striking: HLA-DQA105 carriers had nearly double the risk of forming anti-drug antibodies (hazard ratio 1.90, 95% CI 1.60 to 2.25). The study also revealed an enormous range of immunogenicity depending on carrier status and treatment approach. The highest rate - 92 percent anti-drug antibody formation at one year - occurred in HLA-DQA105 carriers on infliximab monotherapy. The lowest rate was just 10 percent, in non-carriers receiving adalimumab with an immunomodulator (1).

These numbers illustrate why the test matters so much. The difference between a 92 percent and a 10 percent chance of developing antibodies to your biologic is potentially the difference between a treatment that lasts years and one that fails within months. As we covered in our therapeutic drug monitoring guide, tracking drug levels and anti-drug antibodies over time is critical for catching this early - and HLA-DQA1*05 testing can tell you before treatment starts whether you are in a higher-risk category.

New 2025 Data on *05:01 vs *05:05

A 2025 study published in the Journal of Crohn's and Colitis analyzed 1,058 IBD patients and made a clinically important distinction between the two main subtypes (2). HLA-DQA105:01 specifically shortens time to loss of response with infliximab (P = 5.34E-07), while HLA-DQA105:05 shortens time to loss of response with adalimumab (P = 3.20E-05). Crucially, neither subtype was associated with loss of response to vedolizumab (Entyvio) or ustekinumab (Stelara), confirming that HLA-DQA1*05 testing is only informative when anti-TNF drugs are on the table (2).

This subtype-specific data opens the door to more personalized decision-making. A patient who carries *05:01 might do better on adalimumab than infliximab, while a *05:05 carrier might benefit more from infliximab or from combination therapy if adalimumab is preferred.

How the Test Guides Treatment Decisions

The value of HLA-DQA1*05 testing lies in what it can change about your treatment plan. Here is how the results translate into practical clinical decisions.

Carriers vs Non-Carriers

If you carry HLA-DQA105:05 and are starting adalimumab, recent evidence suggests strongly considering combination therapy with an immunomodulator such as azathioprine or methotrexate to reduce the chance of anti-drug antibody formation (2). If you carry HLA-DQA105:01 and your gastroenterologist is considering an anti-TNF, adalimumab monotherapy is often preferred over infliximab because the *05:01 allele was not linked to adalimumab antibodies in the 2025 data (5).

For non-carriers on adalimumab, the evidence suggests that adding an immunomodulator may not provide significant benefit - which can help avoid the added risks of combination therapy, including increased susceptibility to infections and other side effects (2). When weighing the full landscape of treatment options, our guide to choosing the best biologic for Crohn's disease provides a broader framework.

When to Add an Immunomodulator

The decision to add methotrexate or azathioprine alongside an anti-TNF is always a balance of benefit and risk. HLA-DQA1*05 testing adds a concrete data point to that conversation. For carriers, combination therapy reduces immunogenicity dramatically - from 92 percent to substantially lower rates in the PANTS data (1). For non-carriers, the baseline immunogenicity risk is already low enough that monotherapy may be sufficient. This is a conversation to have with your gastroenterologist, factoring in your genotype alongside your disease location, severity, prior surgical history, and personal preferences.

Availability, Cost, and What to Expect from Testing

Pharmacogenomic testing for IBD is still relatively new in clinical practice, but access is expanding. Here is what you need to know about getting tested.

In the US: Labcorp Test 167680

In the United States, Labcorp offers test 167680 - HLA-DQA1*05 Variant Associated With Immunogenicity Risk for Anti-Infliximab and Anti-Adalimumab Antibodies. The test uses next-generation sequencing of exon 2 from a standard blood sample (6). It is available through gastroenterology practices that order Labcorp testing. Out-of-pocket cost estimates for HLA typing panels typically range from about 175 to 640 US dollars when not covered by insurance, though coverage is evolving as the evidence base grows.

In the UK and Elsewhere

In the United Kingdom, HLA-DQA105 research has recruited through the NIHR IBD BioResource across more than 100 hospitals, and pilot programs are testing routine clinical implementation (2). Availability in other countries varies, and your gastroenterologist can advise on local access. In a 345-patient Chinese Han cohort, HLA-DQA105 G variant carriers had a 58.5 percent anti-drug antibody rate versus 42.9 percent in non-carriers (P = 0.004), confirming the relevance of the variant beyond European populations (3).

The most important timing consideration: ask your gastroenterologist about testing before starting anti-TNF therapy, since the results are most valuable when they can shape the initial treatment plan rather than explain a failure after the fact.

Limitations and Ongoing Research

Like any single genetic test, HLA-DQA1*05 testing provides one piece of a larger clinical picture. Understanding what it does not tell you is just as important as understanding what it does.

What the Test Does Not Predict

HLA-DQA1*05 testing predicts antibody formation against anti-TNF drugs - it does not predict disease severity, drug efficacy in non-immunogenic pathways, or side effects like infections. The test is not informative for patients whose first-line choice is a non-TNF biologic such as ustekinumab (Stelara), risankizumab (Skyrizi), guselkumab (Tremfya), mirikizumab (Omvoh), or vedolizumab (Entyvio) (2). Additionally, not every insurer covers the test yet, and formal guidelines from the AGA and ECCO have not universally recommended routine testing, though pilot studies show growing clinical adoption (2).

Evidence in Children and Diverse Populations

In pediatric Crohn's patients, HLA-DQA105 carriers showed a trend toward higher anti-drug antibody development and treatment failure, but the differences did not reach statistical significance in a 2025 pediatric study (4). The authors noted that most children in the study received combination therapy, which may have attenuated the genetic effect. In the Chinese Han cohort mentioned above, the association held at statistically significant levels (P = 0.004), providing evidence that HLA-DQA105 is relevant across diverse populations (3). More research is ongoing to refine the clinical utility in these groups.

Questions to Ask Your Gastroenterologist

If you are about to start an anti-TNF biologic or have lost response to one, consider bringing these questions to your next appointment:

• Am I a candidate for HLA-DQA1*05 testing before starting an anti-TNF biologic?
• If I carry the variant, would you recommend combination therapy with methotrexate or azathioprine, and what are the risks?
• How does my genotype fit with my overall Crohn's severity, prior surgeries, and other risk factors?
• Would you consider a non-TNF biologic (Stelara, Skyrizi, Entyvio) instead if my HLA result suggests high immunogenicity risk?
• How do you plan to monitor drug levels and anti-drug antibodies during treatment?

Bringing a printed or saved copy of your test results to your appointment can help make the conversation more productive. Pharmacogenomics is an evolving field, and not every gastroenterologist routinely orders this test yet - being an informed advocate for yourself can make a real difference.

Frequently Asked Questions

What is HLA-DQA1*05 testing?

HLA-DQA1*05 testing is a blood-based pharmacogenomic test that checks whether you carry a genetic variant linked to a higher risk of forming anti-drug antibodies against anti-TNF biologics like infliximab (Remicade) and adalimumab (Humira). The test uses next-generation sequencing and results typically come back within one to two weeks (6).

Does HLA-DQA1*05 testing predict how well my biologic will work?

Not directly. The test predicts your risk of developing anti-drug antibodies, which can cause loss of response over time. It does not measure how effective the drug will be against your Crohn's inflammation through non-immunogenic pathways. It is one factor among many that your gastroenterologist will consider (1, 2).

Is HLA-DQA1*05 testing useful if I am starting Stelara, Skyrizi, or Entyvio?

No. The 2025 data showed that neither the *05:01 nor *05:05 subtype was associated with loss of response to vedolizumab (Entyvio) or ustekinumab (Stelara) (2). The test is only clinically informative when anti-TNF drugs - infliximab or adalimumab - are being considered.

How common is the HLA-DQA1*05 variant?

Approximately 40 percent of people of European descent carry the HLA-DQA1*05 allele (1). In a recent IBD cohort, about 22.5 percent carried the *05:01 subtype and 20.7 percent carried *05:05 (2). The variant has also been confirmed in Chinese Han populations at clinically significant rates (3).

Can children with Crohn's be tested for HLA-DQA1*05?

Yes, the test can be performed at any age. However, a 2025 pediatric study found that while HLA-DQA1*05 carriers showed a trend toward higher immunogenicity, the differences did not reach statistical significance - possibly because most children in the study were already on combination therapy (4). Your child's gastroenterologist can help weigh whether testing adds value to their treatment plan.

Is HLA-DQA1*05 testing covered by insurance?

Coverage varies by insurer and region. In the US, out-of-pocket costs for HLA typing panels typically range from about 175 to 640 dollars. Formal guidelines from the AGA and ECCO have not yet universally recommended routine testing, which can affect coverage decisions (2). It is worth contacting your insurance provider before testing.

What happens if I already lost response to an anti-TNF - is testing still useful?

Testing can still provide context. If you carry HLA-DQA1*05, it may explain why you developed anti-drug antibodies, which can influence whether your gastroenterologist recommends trying a second anti-TNF with combination therapy or switching to a different biologic class entirely. The results become part of your treatment history.

References

1. Sazonovs A, Kennedy NA, Moutsianas L, et al. HLA-DQA105 Carriage Associated With Development of Anti-Drug Antibodies to Infliximab and Adalimumab in Patients With Crohn's Disease*. Gastroenterology, 2020;158(1):189-199. Read study
2. Zhang Q, Sharip M, Roberts C, Shakweh E, Parkes M, Ahmad T. HLA-DQA105:01 and DQA105:05 inform choice of anti-tumor necrosis factor and concomitant use of immunomodulators in patients with inflammatory bowel disease. Journal of Crohn's and Colitis, 2025;19(11):jjaf195. Read study
3. Wang W, Zhang Q, Zhao J, et al. HLA-DQA105 correlates with increased risk of anti-drug antibody development and reduced response to infliximab in Chinese patients with Crohn's disease*. Gastroenterology Report, 2024. Read study
4. Adler J, et al. HLA DQA105 and Risk of Antitumor Necrosis Factor Treatment Failure and Anti-Drug Antibody Development in Children With Crohn's Disease*. American Journal of Gastroenterology, 2025. Read study
5. Ternette N, Liao H, Satsangi J. Association of the HLA-DQA105 Allelic Gene Variants with Immunogenicity to Anti-TNF therapeutics: Important Differences Between Infliximab and Adalimumab*. Journal of Crohn's and Colitis, 2025;19(4):jjae172. Read study
6. Labcorp. Test 167680: HLA-DQA105 Variant Associated With Immunogenicity Risk for Anti-Infliximab (IFX)/Anti-Adalimumab (ADL) Antibodies*. View test details