PMID- 34946883
OWN - NLM
STAT- MEDLINE
DCOM- 20220214
LR  - 20220214
IS  - 2073-4425 (Electronic)
IS  - 2073-4425 (Linking)
VI  - 12
IP  - 12
DP  - 2021 Nov 30
TI  - HLA-DQA1*05 Associates with Extensive Ulcerative Colitis at Diagnosis: An 
      Observational Study in Children.
LID - 10.3390/genes12121934 [doi]
LID - 1934
AB  - 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 n = 188, Crohn's disease n = 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, 
      p = 0.012). PUCAI at diagnosis (p = 0.078) and the time from UC diagnosis to the 
      first administration of biologic treatment (p = 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 (p = 0.066). HLA-DQA1*05 carriers 
      with CD were less likely to present with both stenosing and penetrating disease 
      (B2B3, p = 0.048) and to have active disease proximal to the ligament of Treitz 
      (L4a) at the worst flare (p = 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.
FAU - Nowak, Jan Krzysztof
AU  - Nowak JK
AUID- ORCID: 0000-0003-0953-2188
AD  - Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan 
      University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland.
FAU - Glapa-Nowak, Aleksandra
AU  - Glapa-Nowak A
AUID- ORCID: 0000-0002-3017-0524
AD  - Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan 
      University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland.
FAU - Banaszkiewicz, Aleksandra
AU  - Banaszkiewicz A
AUID- ORCID: 0000-0001-7684-6887
AD  - Department of Pediatric Gastroenterology and Nutrition, Medical University of 
      Warsaw, 02-091 Warszawa, Poland.
FAU - Iwanczak, Barbara
AU  - Iwanczak B
AD  - Department and Clinic of Pediatrics, Gastroenterology and Nutrition, Wroclaw 
      Medical University, 50-367 Wroclaw, Poland.
FAU - Kwiecien, Jaroslaw
AU  - Kwiecien J
AUID- ORCID: 0000-0002-6764-8261
AD  - Department of Pediatrics, Faculty of Medical Sciences in Zabrze, Medical 
      University of Silesia in Katowice, 41-800 Zabrze, Poland.
FAU - Szaflarska-Poplawska, Anna
AU  - Szaflarska-Poplawska A
AD  - Department of Pediatric Endoscopy and Gastrointestinal Function Testing, 
      Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-067 
      Bydgoszcz, Poland.
FAU - Grzybowska-Chlebowczyk, Urszula
AU  - Grzybowska-Chlebowczyk U
AD  - Department of Pediatrics, Faculty of Medical Sciences, Medical University of 
      Silesia in Katowice, 40-055 Katowice, Poland.
FAU - Osiecki, Marcin
AU  - Osiecki M
AUID- ORCID: 0000-0002-4765-7849
AD  - The Department of Gastroenterology, Hepatology, Feeding Disorders and 
      Paediatrics, The Children's Memorial Health Institute, 04-730 Warsaw, Poland.
FAU - Kierkus, Jaroslaw
AU  - Kierkus J
AD  - The Department of Gastroenterology, Hepatology, Feeding Disorders and 
      Paediatrics, The Children's Memorial Health Institute, 04-730 Warsaw, Poland.
FAU - Holubiec, Magdalena
AU  - Holubiec M
AD  - Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan 
      University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland.
FAU - Chanaj-Kaczmarek, Justyna
AU  - Chanaj-Kaczmarek J
AUID- ORCID: 0000-0001-8892-1450
AD  - Department of Pharmacognosy, Poznan University of Medical Sciences, 4 
      Swiecickiego Street, 60-781 Poznan, Poland.
FAU - Radzikowski, Andrzej
AU  - Radzikowski A
AD  - Department of Pediatric Gastroenterology and Nutrition, Medical University of 
      Warsaw, 02-091 Warszawa, Poland.
FAU - Walkowiak, Jaroslaw
AU  - Walkowiak J
AUID- ORCID: 0000-0001-5813-5707
AD  - Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan 
      University of Medical Sciences, Szpitalna 27/33, 60-572 Poznan, Poland.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20211130
PL  - Switzerland
TA  - Genes (Basel)
JT  - Genes
JID - 101551097
RN  - 0 (HLA-DQ alpha-Chains)
RN  - 0 (HLA-DQA1 antigen)
SB  - IM
MH  - Adolescent
MH  - Child
MH  - Cohort Studies
MH  - Colitis, Ulcerative/*genetics/*immunology/physiopathology
MH  - Crohn Disease/genetics/immunology/physiopathology
MH  - Female
MH  - Genetic Association Studies
MH  - HLA-DQ alpha-Chains/*analysis
MH  - Humans
MH  - Male
MH  - Severity of Illness Index
PMC - PMC8701736
OTO - NOTNLM
OT  - Crohn's disease
OT  - anti-drug antibodies
OT  - colitis
OT  - high-resolution melting
OT  - inflammatory bowel disease
OT  - major histocompatibility complex
OT  - personalized medicine
COIS- J.K.N. reports personal fees from Norsa Pharma within an EU-funded project and 
      grant support from Biocodex. J.W. reports personal fees and grant support from 
      Norsa Pharma within an EU-funded project, personal fees, and non-financial 
      support from Biocodex, BGP Products, Chiesi, Hipp, Humana, Mead Johnson 
      Nutrition, Merck Sharp & Dohme, Nestle, Nutricia, Roche, Sequoia Pharmaceuticals, 
      and Vitis Pharma, outside the submitted work, grants, personal fees and 
      non-financial support from Nutricia Research Foundation Poland, also outside the 
      submitted work. The remaining authors report no conflict of interest.
EDAT- 2021/12/25 06:00
MHDA- 2022/02/15 06:00
PMCR- 2021/11/30
CRDT- 2021/12/24 01:12
PHST- 2021/11/03 00:00 [received]
PHST- 2021/11/27 00:00 [revised]
PHST- 2021/11/28 00:00 [accepted]
PHST- 2021/12/24 01:12 [entrez]
PHST- 2021/12/25 06:00 [pubmed]
PHST- 2022/02/15 06:00 [medline]
PHST- 2021/11/30 00:00 [pmc-release]
AID - genes12121934 [pii]
AID - genes-12-01934 [pii]
AID - 10.3390/genes12121934 [doi]
PST - epublish
SO  - Genes (Basel). 2021 Nov 30;12(12):1934. doi: 10.3390/genes12121934.