Involvement of HLADQA1*05 in Patients with Inflammatory Bowel Disease Treated with Anti-TNF Drugs
<i>Background</i>: Over the past decade, TNF inhibitors such as Infliximab and Adalimumab have become central to Inflammatory Bowel Diseases treatment, greatly enhancing patient outcomes. However, immunogenicity—where anti-drug antibodies diminish effectiveness—remains an issue, often re...
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2025-01-01
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| author | Anna Pau Ilaria Galliano Elisa Barnini Maddalena Dini Antonio Pizzol Alice Ponte Stefano Gambarino Pier Luigi Calvo Massimiliano Bergallo |
| author_facet | Anna Pau Ilaria Galliano Elisa Barnini Maddalena Dini Antonio Pizzol Alice Ponte Stefano Gambarino Pier Luigi Calvo Massimiliano Bergallo |
| author_sort | Anna Pau |
| collection | DOAJ |
| description | <i>Background</i>: Over the past decade, TNF inhibitors such as Infliximab and Adalimumab have become central to Inflammatory Bowel Diseases treatment, greatly enhancing patient outcomes. However, immunogenicity—where anti-drug antibodies diminish effectiveness—remains an issue, often requiring dose changes or combination therapies. Pharmacogenomics is increasingly applied in IBD to personalise treatment, especially since genetic factors like the HLA-DQA1*05 variant heighten the immunogenicity risk with IFX. This study aims to examine the relationship between the HLA-DQA1*05 variant and response loss or antibody development in patients regularly monitored on IFX or ADA. <i>Methods</i>: Sixty-five paediatric IBD patients were enrolled, with therapeutic drug monitoring (TDM) of IFX and ADA, conducted using immunoenzymatic assays. The presence of the HLA-DQA1*05 T>C allele variant was also tested using a Biomole HLA-DQA1 Real-time PCR kit. <i>Results</i>: The HLA-DQA1*05 rs2097432 T>C allele was present in 54% of patients on IFX and 69% of those on ADA. No statistically significant differences were found between HLA carriers and non-carriers across any of the three analysed groups: IFX, ADA and the overall anti-TNFα. <i>Conclusions</i>: Our study suggests that the HLA-DQA1*05 allele does not increase the risk of secondary loss of response to anti-TNF therapy, likely because most patients were on a combination of anti-TNF agents and immunomodulators, which can lower anti-drug antibody production. Testing for HLA-DQA105 can aid in personalising treatment and optimising therapy to minimise immunogenicity risks. |
| format | Article |
| id | doaj-art-99cb6fd524ae42d8883f6b0a4aaa49c4 |
| institution | Kabale University |
| issn | 1010-660X 1648-9144 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Medicina |
| spelling | doaj-art-99cb6fd524ae42d8883f6b0a4aaa49c42025-01-24T13:40:36ZengMDPI AGMedicina1010-660X1648-91442025-01-0161110210.3390/medicina61010102Involvement of HLADQA1*05 in Patients with Inflammatory Bowel Disease Treated with Anti-TNF DrugsAnna Pau0Ilaria Galliano1Elisa Barnini2Maddalena Dini3Antonio Pizzol4Alice Ponte5Stefano Gambarino6Pier Luigi Calvo7Massimiliano Bergallo8Laboratory of Specialistic Pediatry, Department of Public Health and Pediatrics, School of Medicine, University of Turin, 10126 Turin, ItalyLaboratory of Specialistic Pediatry, Department of Public Health and Pediatrics, School of Medicine, University of Turin, 10126 Turin, ItalyLaboratory of Specialistic Pediatry, Department of Public Health and Pediatrics, School of Medicine, University of Turin, 10126 Turin, ItalyLaboratory of Specialistic Pediatry, Department of Public Health and Pediatrics, School of Medicine, University of Turin, 10126 Turin, ItalyUnit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza di Torino, University of Turin, 10126 Turin, ItalyUnit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza di Torino, University of Turin, 10126 Turin, ItalyBioMole srl. Via Quarello 15/A, 10100 Turin, ItalyUnit of Pediatric Gastroenterology, Department of Pediatrics, Città della Salute e della Scienza di Torino, University of Turin, 10126 Turin, ItalyLaboratory of Specialistic Pediatry, Department of Public Health and Pediatrics, School of Medicine, University of Turin, 10126 Turin, Italy<i>Background</i>: Over the past decade, TNF inhibitors such as Infliximab and Adalimumab have become central to Inflammatory Bowel Diseases treatment, greatly enhancing patient outcomes. However, immunogenicity—where anti-drug antibodies diminish effectiveness—remains an issue, often requiring dose changes or combination therapies. Pharmacogenomics is increasingly applied in IBD to personalise treatment, especially since genetic factors like the HLA-DQA1*05 variant heighten the immunogenicity risk with IFX. This study aims to examine the relationship between the HLA-DQA1*05 variant and response loss or antibody development in patients regularly monitored on IFX or ADA. <i>Methods</i>: Sixty-five paediatric IBD patients were enrolled, with therapeutic drug monitoring (TDM) of IFX and ADA, conducted using immunoenzymatic assays. The presence of the HLA-DQA1*05 T>C allele variant was also tested using a Biomole HLA-DQA1 Real-time PCR kit. <i>Results</i>: The HLA-DQA1*05 rs2097432 T>C allele was present in 54% of patients on IFX and 69% of those on ADA. No statistically significant differences were found between HLA carriers and non-carriers across any of the three analysed groups: IFX, ADA and the overall anti-TNFα. <i>Conclusions</i>: Our study suggests that the HLA-DQA1*05 allele does not increase the risk of secondary loss of response to anti-TNF therapy, likely because most patients were on a combination of anti-TNF agents and immunomodulators, which can lower anti-drug antibody production. Testing for HLA-DQA105 can aid in personalising treatment and optimising therapy to minimise immunogenicity risks.https://www.mdpi.com/1648-9144/61/1/102infliximabadalimumabIBDHLA-DQA1 |
| spellingShingle | Anna Pau Ilaria Galliano Elisa Barnini Maddalena Dini Antonio Pizzol Alice Ponte Stefano Gambarino Pier Luigi Calvo Massimiliano Bergallo Involvement of HLADQA1*05 in Patients with Inflammatory Bowel Disease Treated with Anti-TNF Drugs Medicina infliximab adalimumab IBD HLA-DQA1 |
| title | Involvement of HLADQA1*05 in Patients with Inflammatory Bowel Disease Treated with Anti-TNF Drugs |
| title_full | Involvement of HLADQA1*05 in Patients with Inflammatory Bowel Disease Treated with Anti-TNF Drugs |
| title_fullStr | Involvement of HLADQA1*05 in Patients with Inflammatory Bowel Disease Treated with Anti-TNF Drugs |
| title_full_unstemmed | Involvement of HLADQA1*05 in Patients with Inflammatory Bowel Disease Treated with Anti-TNF Drugs |
| title_short | Involvement of HLADQA1*05 in Patients with Inflammatory Bowel Disease Treated with Anti-TNF Drugs |
| title_sort | involvement of hladqa1 05 in patients with inflammatory bowel disease treated with anti tnf drugs |
| topic | infliximab adalimumab IBD HLA-DQA1 |
| url | https://www.mdpi.com/1648-9144/61/1/102 |
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