PMID- 33122841
OWN - NLM
STAT- MEDLINE
DCOM- 20211210
LR  - 20211214
IS  - 1530-0447 (Electronic)
IS  - 0031-3998 (Linking)
VI  - 89
IP  - 2
DP  - 2021 Jan
TI  - HLA class II genes in precision-based care of childhood diseases: what we can 
      learn from celiac disease.
PG  - 307-312
LID - 10.1038/s41390-020-01217-4 [doi]
AB  - Celiac disease (CeD) is a chronic immuno-mediated enteropathy caused by dietary 
      gluten with marked autoimmunity traits. The human leukocyte antigen (HLA) class 
      II heterodimers represent the main predisposing factor, although environmental 
      agents, as viral infection, gut microbiota, and dietary regimen, also contribute 
      to CeD risk. These molecules are involved in autoimmunity as they present 
      self-antigens to autoreactive T cells that have escaped the thymic negative 
      selection. In CeD, the HLA class II risk alleles, DQA1*05-DQB1*02 and 
      DQA1*03-DQB1*03, encode for DQ2.5 and DQ8 heterodimers, and, furthermore, disease 
      susceptibility was found strictly dependent on the dose of these genes. This 
      finding questioned how the expression of HLA-DQ risk genes, and of relative 
      surface protein on antigen-presenting cells, might be relevant for the magnitude 
      of anti-gluten inflammatory response in CeD patients, and impact the natural 
      history of disease, its pathomechanisms, and compliance to dietary treatment. In 
      this scenario, new personalized medical approaches will be desirable to support 
      an early, accurate, and non-invasive diagnosis, and to define genotype-guided 
      preventive and therapeutic strategies for CeD. To reach this goal, a 
      stratification of genetic risk, disease outcome, and therapy compliance based on 
      HLA genotypes, DQ2.5/DQ8 expression measurement and magnitude of T cell response 
      to gluten is mandatory. IMPACT: This article revises the current knowledge on how 
      different HLA haplotypes, carrying the DQ2.5/DQ8 risk alleles, impact the onset 
      of CeD. This review discusses how the expression of susceptibility HLA-DQ genes 
      can determine the risk assessment, outcome, and prevention of CeD. The recent 
      insights on the environmental factors contributing to CeD in childhood are 
      reviewed. This review discusses the use of HLA risk gene expression as a tool to 
      support medical precision approaches for an early and non-invasive diagnosis of 
      CeD, and to define genotype-guided preventive and therapeutic strategies.
FAU - Del Pozzo, Giovanna
AU  - Del Pozzo G
AD  - Institute of Genetics and Biophysics "Adriano Buzzati Traverso", Italian National 
      Council of Research(CNR), Naples, Italy. giovanna.delpozzo@igb.cnr.it.
FAU - Farina, Federica
AU  - Farina F
AD  - Institute of Genetics and Biophysics "Adriano Buzzati Traverso", Italian National 
      Council of Research(CNR), Naples, Italy.
FAU - Picascia, Stefania
AU  - Picascia S
AD  - Institute of Biochemistry and Cell Biology, Italian National Council of 
      Research(CNR), Naples, Italy.
FAU - Laezza, Mariavittoria
AU  - Laezza M
AD  - Institute of Genetics and Biophysics "Adriano Buzzati Traverso", Italian National 
      Council of Research(CNR), Naples, Italy.
FAU - Vitale, Serena
AU  - Vitale S
AD  - Institute of Biochemistry and Cell Biology, Italian National Council of 
      Research(CNR), Naples, Italy.
FAU - Gianfrani, Carmen
AU  - Gianfrani C
AD  - Institute of Biochemistry and Cell Biology, Italian National Council of 
      Research(CNR), Naples, Italy.
AD  - European Laboratory for the Investigation of Food Induced Diseases (ELFID), 
      University Federico II, Naples, Italy.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20201029
PL  - United States
TA  - Pediatr Res
JT  - Pediatric research
JID - 0100714
RN  - 0 (HLA-DQ Antigens)
RN  - 8002-80-0 (Glutens)
SB  - IM
MH  - Celiac Disease/*diagnosis/diet therapy/genetics/immunology
MH  - Clinical Decision-Making
MH  - Diet, Gluten-Free
MH  - Early Diagnosis
MH  - *Genes, MHC Class II
MH  - Genetic Predisposition to Disease
MH  - *Genetic Testing
MH  - Glutens/immunology
MH  - HLA-DQ Antigens/*genetics/immunology
MH  - Humans
MH  - Phenotype
MH  - *Precision Medicine
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - Risk Assessment
MH  - Risk Factors
MH  - T-Lymphocytes/immunology
EDAT- 2020/10/31 06:00
MHDA- 2021/12/15 06:00
CRDT- 2020/10/30 05:51
PHST- 2020/05/19 00:00 [received]
PHST- 2020/09/25 00:00 [accepted]
PHST- 2020/09/17 00:00 [revised]
PHST- 2020/10/31 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2020/10/30 05:51 [entrez]
AID - 10.1038/s41390-020-01217-4 [pii]
AID - 10.1038/s41390-020-01217-4 [doi]
PST - ppublish
SO  - Pediatr Res. 2021 Jan;89(2):307-312. doi: 10.1038/s41390-020-01217-4. Epub 2020 
      Oct 29.