scholarly journals First-degree Relatives of Celiac Disease Patients Have Increased Seroreactivity to Serum Microbial Markers

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1073
Author(s):  
Liisa Viitasalo ◽  
Sari Iltanen ◽  
Heini Huhtala ◽  
Päivi Saavalainen ◽  
Katri Kaukinen ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Celiac Disease ◽  
Environmental Factors ◽  
Membrane Protein ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
First Degree Relatives ◽  
Genetic And Environmental Factors ◽  
Hla Haplotypes

Risk of celiac disease (CD) is increased in relatives of CD patients due to genetic and possible environmental factors. We recently reported increased seropositivity to anti-Saccharomyces cerevisiae (ASCA), Pseudomonas fluorescens-associated sequence (anti-I2) and Bacteroides caccae TonB-linked outer membrane protein (anti-OmpW) antibodies in CD. We hypothesized these markers also to be overrepresented in relatives. Seropositivity and levels of ASCA, anti-I2 and anti-OmpW were compared between 463 first-degree relatives, 58 untreated and 55 treated CD patients, and 80 controls. CD-associated human leukocyte antigen (HLA)-haplotypes and transglutaminase (tTGab) and endomysium (EmA) antibodies were determined. One or more of the microbial antibodies was present in 75% of relatives, 97% of untreated and 87% of treated CD patients and 44% of the controls. The relatives had higher median ASCA IgA (9.13 vs. 4.50 U/mL, p < 0.001), ASCA IgG (8.91 vs. 5.75 U/mL, p < 0.001) and anti-I2 (absorbance 0.74 vs. 0.32, p < 0.001) levels than controls. There was a weak, positive correlation between tTGab and ASCA (r = 0.31, p < 0.001). Seropositivity was not significantly associated with HLA. To conclude, seropositivity to microbial markers was more common and ASCA and anti-I2 levels higher in relatives of CD patients than controls. These findings were not associated with HLA, suggesting the role of other genetic and environmental factors.

scholarly journals The Phenotype of Celiac Disease Has Low Concordance between Siblings, Despite a Similar Distribution of HLA Haplotypes

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 479 ◽  
Author(s):  
Saana Kauma ◽  
Katri Kaukinen ◽  
Heini Huhtala ◽  
Laura Kivelä ◽  
Henna Pekki ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Environmental Factors ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Similar Distribution ◽  
Intestinal Malabsorption ◽  
Sibling Pairs ◽  
Leukocyte Antigen ◽  
Intestinal Symptoms ◽  
Hla Haplotypes

The factors determining the presentation of celiac disease are unclear. We investigated the phenotypic concordance and the distribution of human leukocyte antigen (HLA) risk haplotypes in affected siblings. One hundred sibling pairs were included. Clinical and histological parameters and HLA haplotypes were compared between the first diagnosed indexes and their siblings. The phenotype was categorized into gastrointestinal, extra-intestinal, malabsorption/anemia, and asymptomatic. The phenotype was fully concordant in 21 pairs. The most common concordant phenotype was gastrointestinal (14 pairs). Indexes had more anemia/malabsorption and extra-intestinal symptoms than siblings (45% vs. 20%, p < 0.001 and 33% vs. 12%, p < 0.001, respectively). Twenty siblings and none of the indexes were asymptomatic. The indexes were more often women (81% vs. 63%, p = 0.008). They were also more often seronegative (11% vs. 0%, p = 0.03) and younger (37 vs. 43 year, p < 0.001), and had more severe histopathology (total/subtotal atrophy 79% vs. 58%, p = 0.047) at diagnosis. The indexes and siblings were comparable in other disease features. Pairs with discordant presentation had similar HLA haplotypes more often than the concordant pairs. The phenotype was observed to vary markedly between siblings, with the indexes generally having a more severe presentation. HLA did not explain the differences, suggesting that non-HLA genes and environmental factors play significant roles.

Immunogenetics of Celiac Disease: A Focus on Arab Countries

2020 ◽  
Vol 20 (4) ◽  
pp. 275-285 ◽  
Author(s):  
Nadin Younes ◽  
Salma Younes ◽  
Ola. A. Alsharabasi ◽  
Mohamed E. El Zowalaty ◽  
Ibrahim Mustafa ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Genetic Epidemiology ◽  
Arab World ◽  
Human Leukocyte ◽  
Epidemiological Studies ◽  
Arab Countries ◽  
Global Perspective ◽  
Genetic Profile ◽  
Leukocyte Antigen ◽  
Genetic And Environmental Factors

Celiac Disease (CD) is a complex immunogenic disease mainly triggered by gluten intake in genetically susceptible individuals with a prevalence of 1 in 100-300. CD results from the interplay between genetic and environmental factors. Genetic susceptibility is believed to play a prominent role in the pathogenicity of CD, mainly due to human leukocyte antigen (HLA)-related class II genes. Although CD is wellrecognized among Arab populations, there are few studies on the genetic epidemiology and prevalence of CD in the Arab countries. Therefore, the aim of this review was to highlight the importance of studying this disease in the Arab world in the context of a global perspective. Within the few studies published so far, it was found that Arab populations have a distinctive susceptibility genetic profile from other ethnic groups with the DQ2.5 and DQ8 genotypes that are considered the major genotypes that confer susceptibility among Arab patients with CD. Our findings will pave the way to perform further epidemiological studies that will help identify potential therapeutic targets against CD among Arab patients that are diagnosed with CD.

scholarly journals A Structural and Immunological Basis for the Role of Human Leukocyte Antigen DQ8 in Celiac Disease

Immunity ◽  
2007 ◽  
Vol 27 (1) ◽  
pp. 23-34 ◽  
Author(s):  
Kate N. Henderson ◽  
Jason A. Tye-Din ◽  
Hugh H. Reid ◽  
Zhenjun Chen ◽  
Natalie A. Borg ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
Leukocyte Antigen

scholarly journals TagSNP approach for HLA Risk Allele Genotyping of Saudi Celiac Disease Patients: Effectiveness and Pitfalls

2021 ◽  
Author(s):  
Reham Baaqeel ◽  
Babajan Banaganapalli ◽  
Hadiah Bassam Al Mahdi ◽  
Mohammed A. Salama ◽  
Bakr H. Alhussaini ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Local Population ◽  
Human Leukocyte ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Leukocyte Antigen ◽  
Tag Snps ◽  
Ethnic Populations ◽  
Hla Haplotypes ◽  
Hla Dq2

Background: Celiac disease (CD) is a genetically complex autoimmune disease which is triggered by dietary gluten. Human Leukocyte Antigen (HLA) class II genes are known to act as high-risk markers for CD, where &gt;95% of CD patients carry (HLA)- DQ2 and/or DQ8 alleles. Therefore, this study was conducted to investigate the distribution of HLA haplotypes among Saudi CD patients and healthy controls by using the tag Single Nucleotide Polymorphisms (SNP).Methods: HLA-tag SNPs showing strong linkage value (r2&gt;0.99) were used to predict the HLA DQ2 and DQ8 genotypes in 101 Saudi CD patients and in 103 healthy controls by using Real Time Polymerase Chain Reaction (RT-PCR) technique. Genotype calls were further validated by Sanger sequencing method.Results: A total of 63.7% of CD cases and of 60.2% of controls were predicted to carry HLA-DQ2 and DQ8 heterodimers, either in the homozygous or heterozygous states. The prevalence of DQ8 in our CD patients was predicted to be higher than the patients from other ethnic populations (35.6%). More than 32% of the CD patients were found to be non-carriers of HLA risk haplotypes as predicted by the tag SNPs.Conclusion: This study highlights that the Caucasian specific HLA-tag SNPs would be of limited value to accurately predict CD specific HLA haplotypes in Saudi population, when compared to the Caucasian groups. Prediction of risk haplotypes by tag SNPs in ethnic groups is a good alternate approach as long as the tag SNPs were identified from the local population genetic variant databases.

scholarly journals Celiac Disease Revisited

2021 ◽  
pp. 1-14
Author(s):  
João Calado ◽  
Mariana Verdelho Machado
Keyword(s):  
Celiac Disease ◽  
Systemic Disease ◽  
Human Leukocyte ◽  
Risk Groups ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Serological Tests ◽  
Leukocyte Antigen ◽  
Human Leukocyte Antigen Haplotype ◽  
Circulating Autoantibodies

Celiac disease (CD) is a systemic disease triggered by gluten ingestion in genetically predisposed individuals. It manifests primarily as an autoimmune enteropathy associated with specific circulating autoantibodies and a human leukocyte antigen haplotype (HLA-DQ2 or HLA-DQ8). It afflicts roughly 1% of the population, though the majority of patients remain undiagnosed. Diarrhea and malabsorption are classic manifestations of CD; however, both children and adults can be paucisymptomatic and present extraintestinal manifestations such as anemia, osteoporosis, and abnormal liver tests. CD screening is not recommended for the general population, and it should be focused on high-risk groups. CD diagnosis is challenging and relies on serological tests, duodenal histology, and genetic testing. Particularly difficult presentations to manage are seronegative patients, seropositive patients without villus atrophy, and patients who have started a gluten-free diet before the diagnostic workup. The only proven treatment is a lifelong gluten-free diet. We present an in-depth review on the physiopathology and management of CD, with a particular emphasis on diagnostic challenges.

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