Abstract Background Immunogenicity against anti-TNFα agents is strongly influenced by carriage of the HLA-DQA1*05 allele. Rapid and non-invasive genotyping may help anticipate loss of response and guide therapeutic strategies in inflammatory bowel disease (IBD). A saliva-based test has been proposed as an alternative to conventional molecular genotyping. The aim of the study is to evaluate the diagnostic accuracy of a commercial saliva-based assay for detecting HLA-DQA1*05 compared with blood-test genotyping. Methods A cross-sectional study was conducted at Hospital Clínico Universitario Lozano Blesa (Zaragoza, Spain). Patients with Crohn’s disease (CD) or ulcerative colitis (UC) receiving anti-TNFα therapy were included. Peripheral blood DNA extraction was performed using the MAG-LEAD® system. HLA-DQA1*05 genotyping was conducted in the Department of Immunology using the HLA-FluoGene® platform, based on sequence-specific PCR (PCR-SSP) with fluorimetric detection employing TaqMan® probes. All patients also underwent a commercial saliva test targeting the same allele. Demographic and clinical data were collected. Diagnostic performance metrics included sensitivity, specificity, predictive values, accuracy and Cohen’s kappa. Results Forty-one patients were included (32 CD, 9 UC); 23 (56.1%) were male. Mean age at diagnosis was 38.5 years and median disease duration was 5.2 years. The prevalence of HLA-DQA1*05 was 60%. The saliva test yielded 21 positive, 18 negative and 2 indeterminate results. When compared with standard genotyping (peripheral blood), sensitivity was 95.5%, specificity 100%, positive predictive value 100%, negative predictive value 94.4%, and overall accuracy 97.4%. Concordance was excellent (κ = 0.94). Conclusion The saliva-based assay demonstrated excellent diagnostic accuracy for detecting HLA-DQA1*05, with perfect specificity and near-perfect sensitivity relative to the genotyping performed on the blood sample. Its non-invasive sampling, ease of use and strong agreement support its integration as a rapid screening tool in routine IBD care to guide decisions related to immunogenicity risk and anti-TNFα therapy. References: 1. Sazonovs A, Kennedy NA, Kumar V, et al. HLA-DQA1*05 carriage and the development of anti–TNF antibodies in inflammatory bowel disease. N Engl J Med. 2020;383(12):1131-1143. doi:10.1056/NEJMoa1912454 2. Kennedy NA, Heap GA, Green HD, et al. Association between HLA-DQA1*05 and immunogenicity to anti-TNF therapy in Crohn’s disease: a multicentre cohort study. Lancet Gastroenterol Hepatol. 2019;4(5):341-353. doi:10.1016/S2468-1253(19)30012-3 3. Ben-Horin S, Chowers Y. Loss of response to anti-TNF agents in Crohn’s disease. Aliment Pharmacol Ther. 2011;33(9):987-995. doi:10.1111/j.1365-2036.2011.04612.x 4. Papamichael K, Cheifetz AS. Therapeutic drug monitoring in inflammatory bowel disease: current practice and future directions. Curr Opin Gastroenterol. 2019;35(4):302-310. doi:10.1097/MOG.0000000000000556 Conflict of interest: Ms. Lopez, Julia: No conflict of interest Gargallo-Puyuelo, Carla: No conflict of interest
Lopez et al. (2026) studied this question.