HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children
The human leukocyte antigen (HLA) allele group HLA-DQA1*05 predisposes to ulcerative colitis (UC) and is associated with the development of antibodies against infliximab in patients with inflammatory bowel disease (IBD). Therefore, we hypothesized that the presence of HLA-DQA1*05 correlates with cha...
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2021-11-01
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| author | Jan Krzysztof Nowak Aleksandra Glapa-Nowak Aleksandra Banaszkiewicz Barbara Iwańczak Jarosław Kwiecień Anna Szaflarska-Popławska Urszula Grzybowska-Chlebowczyk Marcin Osiecki Jarosław Kierkuś Magdalena Hołubiec Justyna Chanaj-Kaczmarek Andrzej Radzikowski Jarosław Walkowiak |
| author_facet | Jan Krzysztof Nowak Aleksandra Glapa-Nowak Aleksandra Banaszkiewicz Barbara Iwańczak Jarosław Kwiecień Anna Szaflarska-Popławska Urszula Grzybowska-Chlebowczyk Marcin Osiecki Jarosław Kierkuś Magdalena Hołubiec Justyna Chanaj-Kaczmarek Andrzej Radzikowski Jarosław Walkowiak |
| author_sort | Jan Krzysztof Nowak |
| collection | DOAJ |
| description | The human leukocyte antigen (HLA) allele group HLA-DQA1*05 predisposes to ulcerative colitis (UC) and is associated with the development of antibodies against infliximab in patients with inflammatory bowel disease (IBD). Therefore, we hypothesized that the presence of HLA-DQA1*05 correlates with characteristics of pediatric IBD. Within a multi-center cohort in Poland, the phenotype at diagnosis and worst flare was established and HLA-DQA1*05 status was assessed enabling genotype-phenotype analyses. HLA-DQA1*05 was present in 221 (55.1%) out of 401 children with IBD (UC <i>n</i> = 188, Crohn’s disease <i>n</i> = 213). In UC, the presence of HLA-DQA1*05 was moderately associated with a large extent of colonic inflammation at diagnosis (E4 55% more frequent in HLA-DQA1*05-positive patients, <i>p</i> = 0.012). PUCAI at diagnosis (<i>p</i> = 0.078) and the time from UC diagnosis to the first administration of biologic treatment (<i>p</i> = 0.054) did not differ depending on HLA-DQA1*05 status. The number of days of hospitalization for exacerbation was analyzed in 98 patients for whom sufficient follow-up was available and did not differ depending on HLA-DQA1*05 carriership (<i>p</i> = 0.066). HLA-DQA1*05 carriers with CD were less likely to present with both stenosing and penetrating disease (B2B3, <i>p</i> = 0.048) and to have active disease proximal to the ligament of Treitz (L4a) at the worst flare (<i>p</i> = 0.046). Future research focusing on explaining and preventing anti-TNF immunogenicity should take into account that ADA may develop not only as an isolated reaction to anti-TNF exposure but also as a consequence of intrinsic differences in the early course of UC. |
| first_indexed | 2024-03-10T04:02:41Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T04:02:41Z |
| publishDate | 2021-11-01 |
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| series | Genes |
| spelling | doaj.art-b03664dc3bea4db5b9e35ccdeea675012023-11-23T08:30:35ZengMDPI AGGenes2073-44252021-11-011212193410.3390/genes12121934HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in ChildrenJan Krzysztof Nowak0Aleksandra Glapa-Nowak1Aleksandra Banaszkiewicz2Barbara Iwańczak3Jarosław Kwiecień4Anna Szaflarska-Popławska5Urszula Grzybowska-Chlebowczyk6Marcin Osiecki7Jarosław Kierkuś8Magdalena Hołubiec9Justyna Chanaj-Kaczmarek10Andrzej Radzikowski11Jarosław Walkowiak12Department of Pediatric Gastroenterology and Metabolic Diseases, Poznań University of Medical Sciences, Szpitalna 27/33, 60-572 Poznań, PolandDepartment of Pediatric Gastroenterology and Metabolic Diseases, Poznań University of Medical Sciences, Szpitalna 27/33, 60-572 Poznań, PolandDepartment of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, 02-091 Warszawa, PolandDepartment and Clinic of Pediatrics, Gastroenterology and Nutrition, Wroclaw Medical University, 50-367 Wrocław, PolandDepartment of Pediatrics, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 41-800 Zabrze, PolandDepartment of Pediatric Endoscopy and Gastrointestinal Function Testing, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, 85-067 Bydgoszcz, PolandDepartment of Pediatrics, Faculty of Medical Sciences, Medical University of Silesia in Katowice, 40-055 Katowice, PolandThe Department of Gastroenterology, Hepatology, Feeding Disorders and Paediatrics, The Children’s Memorial Health Institute, 04-730 Warsaw, PolandThe Department of Gastroenterology, Hepatology, Feeding Disorders and Paediatrics, The Children’s Memorial Health Institute, 04-730 Warsaw, PolandDepartment of Pediatric Gastroenterology and Metabolic Diseases, Poznań University of Medical Sciences, Szpitalna 27/33, 60-572 Poznań, PolandDepartment of Pharmacognosy, Poznan University of Medical Sciences, 4 Święcickiego Street, 60-781 Poznan, PolandDepartment of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, 02-091 Warszawa, PolandDepartment of Pediatric Gastroenterology and Metabolic Diseases, Poznań University of Medical Sciences, Szpitalna 27/33, 60-572 Poznań, PolandThe human leukocyte antigen (HLA) allele group HLA-DQA1*05 predisposes to ulcerative colitis (UC) and is associated with the development of antibodies against infliximab in patients with inflammatory bowel disease (IBD). Therefore, we hypothesized that the presence of HLA-DQA1*05 correlates with characteristics of pediatric IBD. Within a multi-center cohort in Poland, the phenotype at diagnosis and worst flare was established and HLA-DQA1*05 status was assessed enabling genotype-phenotype analyses. HLA-DQA1*05 was present in 221 (55.1%) out of 401 children with IBD (UC <i>n</i> = 188, Crohn’s disease <i>n</i> = 213). In UC, the presence of HLA-DQA1*05 was moderately associated with a large extent of colonic inflammation at diagnosis (E4 55% more frequent in HLA-DQA1*05-positive patients, <i>p</i> = 0.012). PUCAI at diagnosis (<i>p</i> = 0.078) and the time from UC diagnosis to the first administration of biologic treatment (<i>p</i> = 0.054) did not differ depending on HLA-DQA1*05 status. The number of days of hospitalization for exacerbation was analyzed in 98 patients for whom sufficient follow-up was available and did not differ depending on HLA-DQA1*05 carriership (<i>p</i> = 0.066). HLA-DQA1*05 carriers with CD were less likely to present with both stenosing and penetrating disease (B2B3, <i>p</i> = 0.048) and to have active disease proximal to the ligament of Treitz (L4a) at the worst flare (<i>p</i> = 0.046). Future research focusing on explaining and preventing anti-TNF immunogenicity should take into account that ADA may develop not only as an isolated reaction to anti-TNF exposure but also as a consequence of intrinsic differences in the early course of UC.https://www.mdpi.com/2073-4425/12/12/1934inflammatory bowel diseasecolitisCrohn’s diseaseanti-drug antibodiespersonalized medicinehigh-resolution melting |
| spellingShingle | Jan Krzysztof Nowak Aleksandra Glapa-Nowak Aleksandra Banaszkiewicz Barbara Iwańczak Jarosław Kwiecień Anna Szaflarska-Popławska Urszula Grzybowska-Chlebowczyk Marcin Osiecki Jarosław Kierkuś Magdalena Hołubiec Justyna Chanaj-Kaczmarek Andrzej Radzikowski Jarosław Walkowiak HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children Genes inflammatory bowel disease colitis Crohn’s disease anti-drug antibodies personalized medicine high-resolution melting |
| title | HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children |
| title_full | HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children |
| title_fullStr | HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children |
| title_full_unstemmed | HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children |
| title_short | HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An Observational Study in Children |
| title_sort | hla dqa1 05 associates with extensive ulcerative colitis at diagnosis an observational study in children |
| topic | inflammatory bowel disease colitis Crohn’s disease anti-drug antibodies personalized medicine high-resolution melting |
| url | https://www.mdpi.com/2073-4425/12/12/1934 |
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