27 The role of ligands of activatory receptor NKG2D in the immune-dependent pathogenesis and evolution of inflammatory bowel disease (IBD)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A26-A26
Author(s):  
Heba Sidahmed ◽  
Shilpa Ravindran ◽  
Harshitha Manjunath ◽  
William Mifsud ◽  
Adrian Charles ◽  
...  
Keyword(s):  
Adult Patients ◽  
Soluble Form ◽  
Nucleotide Polymorphisms ◽  
Healthy Donors ◽  
Allele Variant ◽  
Genes Encoding ◽  
History Of ◽  
Clinical Biomarker ◽  
Inflammatory Bowel ◽  
Allelic Variations

BackgroundLong-term inflammation in IBD is mediated by several immune cells, including T lymphocytes and natural killer (NK) cells, through the engagement of NK group 2D (NKG2D) receptors. Allelic variations of NKG2D ligands (NKG2Dls, MICA/B, ULBP1-3) influence differential levels and localization of protein expression or the release of soluble isoforms. The affinity of interaction with NKG2D can be also affected, modulating the cytotoxic activity of the target cell. Evaluation of these molecular pathways and soluble ligands presents the potential use a clinical biomarker for patient outcomes.MethodsGut tissue biopsies (left and right sides) and peripheral blood were collected from patients. 10 pediatric and 11 adult patients with IBD, 10 patients with gut malignancies and history of IBD were included in the study. Plasma form IBD patients and 10 healthy donors as controls, was used to quantify soluble NKG2DLs (sNKG2DLs) by ELISA (R&D Systems Duo Set). Nucleic acids were extracted from gut biopsies using the BioMasher II (Kimble) and All Prep DNA/RNA universal kit (Qiagen). Single nucleotide polymorphisms (SNPs, N=26) and relative gene expression of NKG2DL genes were conducted by qPCR using Taqman assays.Results9/11 adult patients had diagnosis of ulcerative colitis, compared to 3/10 pediatrics. 5/10 pediatrics had Crohn’s disease and 2/10 unclassified IBD. A trend of prevalence of some allelic variants was detected for most of NKGD2Ls.In addition, mRNA encoding for NKG2DLs was detected commonly, although with heterogeneous quantifications, in all the tissues, including the retrospectively collected malignancies with history of IBD. Interestingly, the levels of sNKG2DLs were higher in pediatric (p<0.001) as compared to adult patients. No or low levels of sNKG2DLs were detectable in healthy donors. Moreover 3/5 patients with the highest level (700–1500 pg/ml) of sMICA had homozygosity at least in one of the rs1051792 or rs1051794 polymorphic site (GG allele variant MICA-129Val or MICA-250Val) that have been reported to be associated with soluble form of MICA.ConclusionsThese results, although preliminary and further investigations are ongoing, suggest the relevance of NKG2D/NKG2DL pathway in the development and evolution of IBD. sNKG2DLs could be detected in most of patients, with different levels and highest concentrations in pediatric patients. In some cases, the presence of sNKG2DLs in the plasma could be associated with defined polymorphisms in genes encoding for these proteins.Ethics ApprovalThis study was approved by Sidra Medicine and Hamad Medical Corporation Ethics Boards; approval number 180402817 and MRC-02-18-096, respectively.

scholarly journals Gene Polymorphisms of NOD2, IL23R, PTPN2 and ATG16L1 in Patients with Crohn’s Disease: On the Way to Personalized Medicine?

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 866
Author(s):  
Peter Hoffmann ◽  
David Lamerz ◽  
Petra Hill ◽  
Marietta Kirchner ◽  
Annika Gauss
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Risk Allele ◽  
University Hospital ◽  
Interleukin 12 ◽  
Nucleotide Polymorphisms ◽  
Bowel Diseases ◽  
History Of ◽  
Inflammatory Bowel ◽  
Genetic And Environmental Factors

Genetic and environmental factors are involved in the pathogenesis of inflammatory bowel diseases (IBD). The study aimed at investigating the potential influence of single nucleotide polymorphisms (SNPs) NOD2 rs2066844, NOD2 rs2066845, NOD2 rs2066847, IL23R rs11209026, PTPN2 rs2542151, PTPN2 rs7234029, and ATG16L1 rs2241880 on the response to immunomodulatory therapies and disease course in Crohn’s disease (CD). This is an uncontrolled retrospective monocentric study including patients from the IBD outpatient clinic of Heidelberg University Hospital. Therapy responses and disease courses were related to genetic findings. 379 patients with CD were included. The presence of at least one PTPN2 rs7234029 risk allele was associated with nonresponse to anti-interleukin-12/23 treatment (89.9% vs. 67.6%, p = 0.005). The NOD2 rs2066844 risk allele was associated with a first-degree family history of colon cancer (12.7% vs. 4.7%, p = 0.02), the ATG16L1 rs2241880 risk allele with ileal CD manifestation (p = 0.027), and the IL23R rs11209026 risk allele with a higher rate of CD-related surgeries per disease year (0.08 vs. 0.02, p = 0.025). The results of this study underline the relevance of genetic influences in CD. The association of the PTPN2 rs7234029 risk allele with nonresponse to anti-interleukin-12/23 treatment in CD patients is a novel finding and requires further investigation.

scholarly journals Effect of TRPV1 and TRPV4 genes polymorphisms on the development of airway hyperresponsiveness in patients with asthma

2021 ◽  
pp. 38-44
Author(s):  
O. O. Kotova ◽  
D. E. Naumov ◽  
E. Yu. Afanas'eva ◽  
J. M. Perelman
Keyword(s):  
Airway Hyperresponsiveness ◽  
Challenge Test ◽  
Lower Probability ◽  
Nucleotide Polymorphisms ◽  
Internal Factor ◽  
Single Nucleotide ◽  
Asthma Patients ◽  
Genes Encoding ◽  
Basic Parameters ◽  
Allelic Variations

Introduction. A change in the level of relative humidity of the inhaled air can lead to the appearance of symptoms of airway hyperresponsiveness (AHR) in patients with asthma. Allelic variations of the TRPV genes encoding osmotic receptors may serve as an internal factor predisposing to the development of respiratory manifestations in response to an osmotic trigger.Aim. The aim of the study was to establish the contribution of some single nucleotide polymorphisms (SNPs) of TRPV1 and TRPV4 to the development of osmotic AHR in asthma patients.Materials and methods. Three hundred patients with mild and moderate asthma were enrolled in the study. Osmotic AHR was diagnosed using bronchoprovocation tests with inhalation of distilled water, hypertonic saline (4.5% NaCl) or by treadmill exercise challenge test. Three SNPs (rs222747, rs224534 и rs8065080) of TRPV1 and two SNPs (rs6606743, rs7971845) of TRPV4 were geno- typed.Results. Carriage of the AA genotype for rs6606743 was associated with a lower probability of developing hypo-osmotic-induced bronchospasm. This result was confirmed in recessive (OR 0.43 95% CI [0.19; 0.94], p=0.02) and Logadditive (OR 0.62 95% CI [0.4; 0.96], p=0.03) inheritance models. Besides, in patients with the AA genotype, a less pronounced decrease in all basic parameters of lung function was observed as compared with GG and ΔG genotypes (ΔFVC, ΔPEF and ΔFEF75 - p<0.01; ΔFEV1 ΔFEV1/FVC, ΔFEF50 and ΔMMEF - p<0.001).Conclusion. A protective effect of the AA genotype for rs6606743 of TRPV4 was revealed in relation to the formation of hypoosmotic AHR.

scholarly journals The Role of Vitamin D Deficiency Prevention in Improving Obstetric, Perinatal and Long-Term Outcomes

2020 ◽  
pp. 35-40
Author(s):  
Iu.V. Davydova ◽  
◽  
A.Iu. Lymanska ◽  
Yu.P. Neroznak ◽  
◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Vitamin D3 ◽  
First Trimester ◽  
Soluble Form ◽  
High Dose ◽  
Fetoplacental Complex ◽  
History Of ◽  
Inflammatory Bowel

Much attention is paid to deficiencies prevention during pregnancy, since they negatively affect not only metabolic processes, including fetoplacental complex, but also the condition of the fetus, the newborn, and physical and mental development of the child in the future. Summarizing the recommendations for the use of vitamin D during pregnancy, it should be noted that the typical prophylactic dose is 400 IU/day starting from the first trimester. However, we should consider the use of corrective doses in the second and third trimesters when the fetal skeleton is growing and developing. A high dose of vitamin D (2000 IU/day) is recommended for women at high risk of developing hypertensive complications of pregnancy (a history of preeclampsia, in particular, arising before 28 weeks, arterial hypertension, chronic kidney disease), as well as pregnant women with comorbidity (systemic red lupus, rheumatoid arthritis, multiple sclerosis, cardiovascular disease, inflammatory bowel disease, oncological pathology). For women at risk of vitamin D deficiency, the recommended dose is less than 1000 IU/day. In case of confirmed vitamin D deficiency (<25-30 nmol/L), a correction dose of 2000-4000 IU/day is prescribed for 11 weeks to provide a cumulative dose of about 150,000 or 300,000 units in the second or third trimesters. Today, a sufficient number of vitamin D preparations are presented on the pharmaceutical market of Ukraine, among which one should pay attention to "Olidetrim" (Polpharma, Poland) in the form of oil solution in capsules ensuring its absorption and assimilation. Depending on the dosage, each capsule of the preparation contains 2000 IU or 4000 IU of vitamin D3 (cholecalciferol). In addition to the fat-soluble form, vitamin D preparation Aquadetrim® (Polpharma, Poland) is registered and successfully used in Ukraine. This is a unique form of vitamin D3 based on nanomycellae, which provides better absorption of vitamin D in the intestine. Key words: vitamin D, deficiency, pregnancy, fetus, prevention.

scholarly journals An analysis and survey of interleukin-10 receptor mutation in inflammatory bowel disease (IBD) in the first Iranian IBD cohort

2019 ◽  
Vol 43 (4) ◽  
pp. 185-189
Author(s):  
Razieh Khoshnevisan ◽  
Fariba Vakili ◽  
Christoph Klein ◽  
Daniel Kotlarz ◽  
Maryam Nasirian ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Onset ◽  
Interleukin 10 ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Dna Contents ◽  
Genes Encoding ◽  
Inflammatory Bowel ◽  
Total Dna

Abstract Background Early-onset inflammatory bowel disease (IBD) is classified into Crohn’s disease (CD), ulcerative colitis (UC) and unclassified disorders, which has a chronic, relapsing course and can result in substantial long-term morbidity. IBD is a multifactorial disorder with genetic susceptibility, immunological predisposition and environmental triggers. The objective of this study was to generally determine the prevalence of IL10R mutation in IBD patients in Isfahan, Iran. We performed sequencing of all exons in IL10RA and IL10RB in a cohort of IBD patients and healthy controls. Methods Total DNA contents of 76 patients and 50 healthy controls were extracted from whole blood and polymerase chain reaction (PCR) amplifications and sequencing of whole exons in IL10R were performed. Results Overall, we determined 13 single nucleotide polymorphisms (SNPs) in all IL10R genes. Of them, rs3135932 and rs2229113 of the IL10RA1 gene, in exons 4 and 7, respectively, were significantly associated with IBD occurrence in patients. Conclusions Our results also confirmed that early-onset IBD could be attributed to a synergistic effect of several variant alleles of the genes encoding IL10 receptors. These variants, alone, could only give rise to a sub-clinical manifestation of IBD.

Corticosteroids in Inflammatory Bowel Disease patients: a practical guide for physicians.

2020 ◽  
Vol 15 ◽  
Author(s):  
Maria Carla Di Paolo ◽  
Cristiano Pagnini ◽  
Maria Giovanna Graziani
Keyword(s):  
Severe Disease ◽  
Unknown Etiology ◽  
History Of Disease ◽  
Bowel Diseases ◽  
Literature Evidence ◽  
History Of ◽  
Inflammatory Bowel ◽  
Favorable Safety ◽  
Pass Metabolism

: Inflammatory bowel diseases (IBDs) are chronic conditions characterized by unknown etiology and pathogenesis with deregulation of mucosal immunity. Among possible treatments, corticosteroids, already available from the 50’, are still the mainstay of treatment for moderate-severe disease. Nonetheless, the use of steroids is still largely empirical and solid evidence about therapeutic schemes are lacking. Moreover, due to the important side-effects and for the unsatisfactory impact on long-term natural history of disease, the steroid sparing has become an important therapeutic goal in IBD management. Besides conventional steroids, the so called “low bioavailability” steroids, which are steroids with high affinity for peripheral receptors and elevated hepatic first-pass metabolism, have demonstrated efficacy and more favorable safety profile. In the present review of the literature evidence of efficacy and safety of conventional and low bioavailability steroids in IBD patients are evaluated, and practical suggestions for a correct use in clinical practice are presented according to the current clinical guidelines.

scholarly journals Parathyroid hormone Gene and Genes Involved in the Maintenance of Vitamin D Levels Association with Mandibular Retrognathism

2021 ◽  
Vol 11 (5) ◽  
pp. 369
Author(s):  
Erika Calvano Küchler ◽  
Caio Luiz Bitencourt Reis ◽  
Guido Marañón-Vásquez ◽  
Paulo Nelson-Filho ◽  
Mírian Aiko Nakane Matsumoto ◽  
...  
Keyword(s):  
Statistical Significance ◽  
Interaction Model ◽  
Distribution Analysis ◽  
Nucleotide Polymorphisms ◽  
Allele Distribution ◽  
Vitamin D Levels ◽  
Lateral Cephalograms ◽  
Genes Encoding ◽  
Chi Squared ◽  
Mandibular Retrognathism

In this study we evaluated whether single nucleotide polymorphisms (SNPs) in the genes encoding PTH, VDR, CYP24A1, and CYP27B1 were associated with mandibular retrognathism (MR). Samples from biologically-unrelated Brazilian patients receiving orthodontic treatment were included in this study. Pre-orthodontic lateral cephalograms were used to determine the phenotype. Patients with a retrognathic mandible were selected as cases and those with an orthognathic mandible were selected as controls. Genomic DNA was used for genotyping analysis of SNPs in PTH (rs694, rs6256, and rs307247), VDR (rs7975232), CYP24A1 (rs464653), and CYP27B1 (rs927650). Chi-squared or Fisher’s tests were used to compare genotype and allele distribution among groups. Haplotype analysis was performed for the SNPs in PTH. The established alpha was p < 0.05. Multifactor dimensionality reduction (MDR) was used to identify SNP–SNP interactions. A total of 48 (22 males and 26 females) MR and 43 (17 males and 26 females) controls were included. The linear mandibular and the angular measurements were statistically different between MR and controls (p < 0.05). In the genotype and allele distribution analysis, the SNPs rs694, rs307247, and rs464653 were associated with MR (p < 0.05). MDR analyses predicted the best interaction model for MR was rs694–rs927650, followed by rs307247–rs464653–rs927650. Some haplotypes in the PTH gene presented statistical significance. Our results suggest that SNPs in PTH, VDR, CYP24A1, and CYP27B1 genes are associated with the presence of mandibular retrognathism.

scholarly journals SAT0462 ASSESSMENT OF BONE MINERAL DENSITY IN INFLAMMATORY BOWEL DISEASE

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1188.1-1188
Author(s):  
C. Daldoul ◽  
N. El Amri ◽  
K. Baccouche ◽  
H. Zeglaoui ◽  
E. Bouajina
Keyword(s):  
Bone Mineral Density ◽  
Inflammatory Bowel Disease ◽  
Bone Mineral ◽  
Bowel Disease ◽  
Mineral Density ◽  
Femoral Site ◽  
Significant Difference ◽  
History Of ◽  
Inflammatory Bowel ◽  
The Mean

Background:Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is considered as a risk factor of low bone mineral density (BMD). In fact, the prevalence of osteoporosis ranges from 17% to 41% in IBD patients. The possible contributing factors may include malabsorption, glucocorticoid treatment and coexisting comorbiditiesObjectives:The purpose of our work was to determine the frequency and the determinants of osteoporosis in patients with IBD and to assess whether there is a difference in BMD status between UC and CD.Methods:This is a retrospective study, over a period of 5 years (from January 2014 to December 2018) and including patients followed for IBD who had a measurement of BMD by DEXA. Clinical, anthropometric and densitometric data (BMD at the femoral and vertebral site) were recorded. The WHO criteria for the definition of osteoporosis and osteopenia were applied.Results:One hundred and five patients were collected; among them 45 were men and 60 were women. The average age was 45.89 years old. The average body mass index (BMI) was 25.81 kg/m2 [16.44-44.15]. CD and UC were diagnosed in respectively 57.1% and 42.9%. A personal history of fragility fracture was noted in 4.8%. Hypothyroidism was associated in one case. Early menopause was recorded in 7.6%. 46.8% patients were treated with corticosteroids. The mean BMD at the vertebral site was 1.023 g/cm3 [0.569-1.489 g/cm3]. Mean BMD at the femoral site was 0.920g/cm3 [0.553-1.286g / cm3]. The mean T-score at the femoral site and the vertebral site were -1.04 SD and -1.27 SD, respectively. Osteoporosis was found in 25.7% and osteopenia in 37.1%. Osteoporosis among CD and UC patients was found in respectively 63% and 37%. The age of the osteoporotic patients was significantly higher compared to those who were not osteoporotic (52.23 vs 43.67 years, p = 0.01). We found a significantly higher percentage of osteoporosis among men compared to women (35.6% vs 18.3%, p=0.046). The BMI was significantly lower in the osteoporotic patients (23.87 vs 26.48 kg/m2, p=0.035) and we found a significant correlation between BMI and BMD at the femoral site (p=0.01). No increase in the frequency of osteoporosis was noted in patients treated with corticosteroids (27.9% vs 21.6%, p=0.479). Comparing the UC and CD patients, no difference was found in baseline characteristics, use of steroids or history of fracture. No statistically significant difference was found between UC and CD patients for osteoporosis(p=0.478), BMD at the femoral site (p=0.529) and at the vertebral site (p=0.568).Conclusion:Osteoporosis was found in 25.7% of IBD patients without any difference between CD and UC. This decline does not seem to be related to the treatment with corticosteroids but rather to the disease itself. Hence the interest of an early screening of this silent disease.Disclosure of Interests:None declared

scholarly journals A102 ADVERSE PREGNANCY-RELATED OUTCOMES IN WOMEN WITH INFLAMMATORY BOWEL DISEASE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 77-79
Author(s):  
Y Hanna ◽  
P Tandon ◽  
V W Huang
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Pregnancy Outcomes ◽  
Adverse Pregnancy Outcomes ◽  
Categorical Variables ◽  
History Of ◽  
Inflammatory Bowel ◽  
Adverse Pregnancy ◽  
Aspirin Prophylaxis

Abstract Background Women with active inflammatory bowel disease (IBD) are at increased risk of adverse pregnancy outcomes such as preeclampsia. Though aspirin prophylaxis is prescribed in the general population (prior to 16 weeks’ gestation) for those at high-risk of preeclampsia, its use in patients with IBD has not been established. Aims To determine the frequency of and risk factors for adverse pregnancy outcomes in women with IBD, and to evaluate the risk for preeclampsia and the use of aspirin for primary prevention. Methods All pregnant women with IBD (Crohns disease (CD), ulcerative colitis (UC) and IBD-unclassified (IBDU)) seen at Mount Sinai Hospital from 2016–2020 were retrospectively identified. Demographics, reproductive history, and IBD characteristics including therapy and activity during pregnancy were recorded. Adverse pregnancy outcomes were also identified. Active disease during pregnancy was defined as a fecal calprotectin &gt; 250 ug/g and/or using clinical disease activity scores. Categorical variables were compared using the Chi-square (x2) test and continuous variables using the Mann-Whitney test. A two-sided p-value less than 0.05 was considered statistically significant. Results 127 patients (66 with CD, 60 with UC, 1 with IBDU) were included with a median age of 32 years at conception. The majority were Caucasian (70.9%), married (82.7%), completed post-secondary education (69.3%), had no prior or current smoking (78.7%) or alcohol use history (67.7%), and had no other comorbidities (81.9%). 50.4% of women had a prior pregnancy. 3 had a history of preeclampsia and 15/127 were prescribed aspirin prophylaxis. 73.2% of women were in clinical remission at conception. Compared to women with CD, women with UC were more likely to have infants with low birth weight (LBW) (p=0.031), small for gestational age (SGA) (p=0.002) and had higher rates of active IBD during pregnancy (p=0.005). 13 women with IBD developed preeclampsia (6 with UC and 7 with CD). IBD type (p=0.844) and disease activity (p=0.308) were not associated with preeclampsia. Married women (p=0.001) while those who had a preconception consultation (50/127) (p=0.009) had lower rates of preeclampsia while those with a prior history of preeclampsia had higher rates (p=0.002). Among women who developed preeclampsia, pregnancy outcomes were comparable to those who did not. Women on aspirin prophylaxis (5/13) had a higher rate of preeclampsia (p=0.012), although they were also more likely to have a history of preeclampsia (p=0.002). Aspirin use was not associated with subsequent disease activity in pregnancy (p=0.830). Conclusions Women receiving aspirin prophylaxis had higher rates of preeclampsia, likely owing to a higher baseline risk. Preeclampsia prevention with aspirin prophylaxis does not appear to result in disease flares but larger studies are needed to confirm this finding. Funding Agencies None

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