HLA-DQA1*05 Variant Associated With Immunogenicity Risk for Anti-Infliximab (IFX)/Anti-Adalimumab (ADL) Antibodies

Whole blood or buccal swabs

One adult tube or four buccal swabs

One pediatric tube or two buccal swabs

Lavender-top (EDTA) tube or four buccal swabs in a sealed envelope (buccal swab kit). If submitting buccal swabs, please use kit provided by Labcorp. To obtain the buccal swab kit or to discuss other specimen types, please call 800-533-1037 or email [email protected].

Standard phlebotomy or follow instructions on buccal swab kit

Maintain specimen at room temperature. Do not refrigerate or freeze. 

Improper collection tube; mislabeled specimen

This test identifies the HLA-DQA1*05 variant. Carriers of this variant allele in either one copy (heterozygous) or two copies (homozygous) have a 75% higher risk of anti-infliximab (anti-IFX) or anti-adalimumab (anti-ADL) antibodies compared with noncarriers (relative risk for carriers, 1.75, 95% Cl, 1.37-2.25, according to Solitano et al in the latest systematic review and meta-analysis of 13 studies, including 3,756 patients for a median follow-up of 12 months).¹

Noncarrier patients still developed immunogenicity, albeit at a lower incidence (20% vs 35%).¹ Based on a 41% prevalence of variants (as found in predominantly Europeans and North Americans), a positive result on this test carries a positive predictive value (PPV) for immunogenicity of 30%. A negative result on this test indicates noncarrier status and does not mean the patient cannot develop anti-IFX or anti-ADL; it only suggests that the patient may be at decreased risk, with a negative predictive value (NPV) for immunogenicity of 80%.

The use of concomitant immunosuppressive therapy mitigates but does not eliminate the risk of immunogenicity in both HLA-DQA1*05 variant carriers and noncarriers.¹ In two cohorts where proactive therapeutic drug monitoring (TDM) in infliximab (IFX) or adalimumab (ADL) was routinely performed, the presence of the HLA-DQA1*05 variant was not associated with increased risk of immunogenicity.^2,3

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

Genotyping for the DQA1 locus is performed using next-generation sequencing (NGS) of exon 2 and reported at G group resolution. A G group includes all alleles with identical nucleotide sequences encoding the antigen recognition site. Results are reported as "positive" or "negative." Positive indicates the presence of one copy (heterozygous) or two copies (homozygous) of the HLA-DQA1*05 variant allele.

1. Solitano V, Facciorusso A, McGovern DPB, et al. HLA-DQA1*05 Genotype and Immunogenicity to Tumor Necrosis Factor-a Antagonists: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol. 2023 Nov;21(12):3019-3029.e5. PubMed 37061107

2. Colman RJ, Xiong Y, Mizuno T, et al. Antibodies-to-infliximab accelerate clearance while does intensification reverses immunogenicity and recaptures clinical response in pediatric Crohn's disease. Aliment Pharmacol Ther. 2022 Mar;55(5):593-603. PubMed 34935161

3. Spencer EA, Stachelski J, Dervieux T, Dubinsky MC. Failure to Achieve Target Drug Concentrations During Induction and Not HLA-DQA1*05 Carriage Is Associated With Antidrug Antibody Formation in Patients With Inflammatory Bowel Disease. Gastroenterology. 2022 May;162(6):1746-1748.e3. PubMed 35026235