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Article ; Online: Editorial: Peering through the fog-New tools to assess neurocognitive symptoms in coeliac disease.

Villafuerte Gálvez, Javier A / Leffler, Daniel A

2024

Language	English
Publishing date	2024-04-21
Publishing country	England
Document type	Editorial
ZDB-ID	639012-2
ISSN	1365-2036 ; 0269-2813 ; 0953-0673
ISSN (online)	1365-2036
ISSN	0269-2813 ; 0953-0673
DOI	10.1111/apt.17979
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Article ; Online: Editorial: coeliac disease-it's a family affair.

Therrien, Amelie / Leffler, Daniel A

Alimentary pharmacology & therapeutics

2021 Volume 54, Issue 7, Page(s) 967–968

MeSH term(s)	Celiac Disease/diagnosis ; Humans
Language	English
Publishing date	2021-09-16
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	639012-2
ISSN	1365-2036 ; 0269-2813 ; 0953-0673
ISSN (online)	1365-2036
ISSN	0269-2813 ; 0953-0673
DOI	10.1111/apt.16552
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Article ; Online: Inside the Mind of a Cereal Killer: New Insights Into the Effect of Celiac Disease on Central Nervous Systems Function.

Freitag, Tobias L / Leffler, Daniel A

Gastroenterology

2020 Volume 158, Issue 8, Page(s) 2043–2045

MeSH term(s)	Celiac Disease/diagnosis ; Cognition ; Edible Grain ; Humans ; White Matter
Language	English
Publishing date	2020-04-02
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2020.03.068
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Zs.MO 572: Show issues

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Article ; Online: Gluten immunogenic peptides: is knowing half the battle?

Therrien, Amelie / Leffler, Daniel A

The American journal of clinical nutrition

2020 Volume 112, Issue 5, Page(s) 1147–1148

MeSH term(s)	Celiac Disease ; Follow-Up Studies ; Glutens ; Humans ; Peptides
Chemical Substances	Peptides ; Glutens (8002-80-0)
Language	English
Publishing date	2020-07-15
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	280048-2
ISSN	1938-3207 ; 0002-9165
ISSN (online)	1938-3207
ISSN	0002-9165
DOI	10.1093/ajcn/nqaa228
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Article ; Online: Response.

Grossberg, Laurie B / Leffler, Daniel A

Gastrointestinal endoscopy

2018 Volume 88, Issue 1, Page(s) 205

Language	English
Publishing date	2018
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	391583-9
ISSN	1097-6779 ; 0016-5107
ISSN (online)	1097-6779
ISSN	0016-5107
DOI	10.1016/j.gie.2018.03.010
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Zs.MO 519: Show issues

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Article ; Online: Phenome-wide Mendelian randomization analysis reveals multiple health comorbidities of coeliac disease.

Yuan, Shuai / Jiang, Fangyuan / Chen, Jie / Lebwohl, Benjamin / Green, Peter H R / Leffler, Daniel / Larsson, Susanna C / Li, Xue / Ludvigsson, Jonas F

EBioMedicine

2024 Volume 101, Page(s) 105033

Abstract: Background: Coeliac disease (CeD) has been associated with a broad range of diseases in observational data; however, whether these associations are causal remains undetermined. We conducted a phenome-wide Mendelian randomization analysis (MR-PheWAS) to ... ...

Abstract	Background: Coeliac disease (CeD) has been associated with a broad range of diseases in observational data; however, whether these associations are causal remains undetermined. We conducted a phenome-wide Mendelian randomization analysis (MR-PheWAS) to investigate the comorbidities of CeD. Methods: Single nucleotide polymorphisms (SNPs) associated with CeD at the genome-wide significance threshold and without linkage disequilibrium (R Findings: Genetic liability to CeD was associated with 68 clinical outcomes in the UK Biobank, and 38 of the associations were replicated in the FinnGen study. Genetic liability to CeD was associated with a higher risk of several autoimmune diseases (type 1 diabetes and its complications, Graves' disease, Sjögren syndrome, chronic hepatitis, systemic and cutaneous lupus erythematosus, and sarcoidosis), non-Hodgkin's lymphoma, and osteoporosis and a lower risk of prostate diseases. The associations for type 1 diabetes and non-Hodgkin's lymphoma attenuated when excluding SNPs in the MHC region, indicating shared genetic aetiology. Interpretation: This study uncovers multiple clinical outcomes associated with genetic liability to CeD, which suggests the necessity of comorbidity monitoring among this population. Funding: This project was funded by Karolinska Institutet and the Swedish Research Council.
MeSH term(s)	Male ; Humans ; Celiac Disease/epidemiology ; Celiac Disease/genetics ; Diabetes Mellitus, Type 1 ; Genome-Wide Association Study ; Mendelian Randomization Analysis ; Comorbidity ; Lymphoma, Non-Hodgkin ; Polymorphism, Single Nucleotide
Language	English
Publishing date	2024-02-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2024.105033
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Article ; Online: Older age of celiac disease diagnosis and risk of autoimmune disease: A nationwide matched case-control study.

Yuan, Shuai / Leffler, Daniel / Lebwohl, Benjamin / Green, Peter H R / Larsson, Susanna C / Söderling, Jonas / Sun, Jiangwei / Ludvigsson, Jonas F

Journal of autoimmunity

2024 Volume 143, Page(s) 103170

Abstract: Objectives: Celiac disease (CeD) has been linked to an increased risk of other autoimmune diseases, yet the impact of delayed CeD diagnosis on risk of developing additional autoimmune diseases remains uncertain. We investigated this through a nationwide ...

Abstract	Objectives: Celiac disease (CeD) has been linked to an increased risk of other autoimmune diseases, yet the impact of delayed CeD diagnosis on risk of developing additional autoimmune diseases remains uncertain. We investigated this through a nationwide matched case-control study. Methods: Using the ESPRESSO cohort with histophatology data from Sweden's 28 pathology departments, we assessed 46,575 biopsy-confirmed CeD cases from 1964 to 2017. We extracted 225,295 matched controls without histopathology information from the Swedish Total Population Register. Autoimmune disease was defined through diagnostic codes in the National Patient Register. Through conditional logistic regression we estimated odds ratio (OR) of autoimmune disease up until CeD diagnosis/matching date comparing CeD cases to controls across different age strata. Results: A total of 3059 (6.6 %) CeD patients and 4076 (1.8 %) controls had earlier autoimmune disease. The overall OR for autoimmune disease in CeD was 3.50 (95%CI 3.32-3.70). The risk of autoimmune disease did not escalate with increasing age at CeD diagnosis. Compared with controls, the OR of autoimmune disease in CeD patients was 7.70 (95%CI 4.71-12.57) in those diagnosed with CeD in 0-4 years, 19.02 (95%CI 13.80-26.23) in 5-9 years, 6.18 (95%CI 5.14-7.44) in 10-14 years, 4.80 (95%CI 3.97-5.79) in 15-19 years, 4.24 (95%CI 3.55-5.07) in 20-29 years, 4.65 (95%CI 3.93-5.51) in 30-39 years, 3.67 (95%CI 3.30-4.09) in 40-59 years, and 1.67 (95%CI 1.50-1.85) in ≥60 years. Conclusions: This study revealed an increased risk of autoimmune disease among CeD patients compared with controls. However, older age at CeD diagnosis did not seem to escalate the risk of autoimmune diseases.
MeSH term(s)	Humans ; Aged ; Case-Control Studies ; Celiac Disease/diagnosis ; Celiac Disease/epidemiology ; Celiac Disease/pathology ; Autoimmune Diseases/diagnosis ; Autoimmune Diseases/epidemiology ; Logistic Models ; Biopsy
Language	English
Publishing date	2024-01-28
Publishing country	England
Document type	Journal Article
ZDB-ID	639452-8
ISSN	1095-9157 ; 0896-8411
ISSN (online)	1095-9157
ISSN	0896-8411
DOI	10.1016/j.jaut.2024.103170
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Zs.A 2368: Show issues

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Article ; Online: The coumarin osthole is a non-electrophilic agonist of TRPA1.

Torres, Karen V / Pantke, Sebastian / Rudolf, Daniel / Eberhardt, Mirjam M / Leffler, Andreas

Neuroscience letters

2022 Volume 789, Page(s) 136878

Abstract: The naturally occurring coumarin osthole has antipruritic properties, and recent reports suggest that this effect is due an inhibition or desensitization of the cation channels TRPV1 and TRPV3. Osthole was also suggested to activate TRPA1, an effect that ...

Abstract	The naturally occurring coumarin osthole has antipruritic properties, and recent reports suggest that this effect is due an inhibition or desensitization of the cation channels TRPV1 and TRPV3. Osthole was also suggested to activate TRPA1, an effect that should rather be pruritic than antipruritic. Here we characterized the effects of osthole on TRPA1 by means of ratiometric calcium imaging and patch clamp electrophysiology. In HEK 293 expressing human (h) TRPA1, osthole induced a concentration-dependent increase in intracellular calcium that was inhibited by the TRPA1-inhibitor A967079. In mouse dorsal root ganglion (DRG) cells, osthole induced a strong calcium-influx that was partly mediated by TRPA1. Osthole evoked fully reversible membrane currents in whole-cell as well as cell-free inside-out recordings on hTRPA1. Osthole failed to activate the mutant hTRPA1-S873V/T874L, a previously described binding site for the non-electrophilic TRPA1-agonists menthol and carvacrol. The combined application of osthole and carvacrol diminished channel activation, suggesting a competitive binding. Finally, osthole failed to activate TRPM8 and TRPV4 but induced a modest activation of hTRPV1 expressed in HEK 293 cells. We conclude that osthole is a potent non-electrophilic agonist of TRPA1. The relevance of this property for the antipruritic effects needs to be further explored.
MeSH term(s)	Animals ; Antipruritics/pharmacology ; Calcium/metabolism ; Coumarins/pharmacology ; Cymenes ; Ganglia, Spinal/metabolism ; HEK293 Cells ; Humans ; Menthol/pharmacology ; Mice ; TRPA1 Cation Channel/metabolism ; TRPV Cation Channels/metabolism ; Transient Receptor Potential Channels/metabolism
Chemical Substances	Antipruritics ; Coumarins ; Cymenes ; TRPA1 Cation Channel ; TRPA1 protein, human ; TRPV Cation Channels ; Transient Receptor Potential Channels ; Trpa1 protein, mouse ; Trpv4 protein, mouse ; Menthol (1490-04-6) ; carvacrol (9B1J4V995Q) ; Calcium (SY7Q814VUP) ; osthol (XH1TI1759C)
Language	English
Publishing date	2022-09-15
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2022.136878
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Article ; Online: Celiac disease diagnosis and management: a 46-year-old woman with anemia.

Leffler, Daniel

JAMA

2011 Volume 306, Issue 14, Page(s) 1582–1592

Abstract: Celiac disease is one of the most prevalent autoimmune gastrointestinal disorders, but as the case of Ms J illustrates, diagnosis is often delayed or missed. Based on serologic studies, the prevalence of celiac disease in many populations is estimated to ...

Abstract	Celiac disease is one of the most prevalent autoimmune gastrointestinal disorders, but as the case of Ms J illustrates, diagnosis is often delayed or missed. Based on serologic studies, the prevalence of celiac disease in many populations is estimated to be approximately 1% and has been increasing steadily over the last 50 years. Evaluation for celiac disease is generally straightforward and uses commonly available serologic tests; however, the signs and symptoms of celiac disease are nonspecific and highly heterogeneous, making diagnosis difficult. Although celiac disease is often considered a mild disorder treatable with simple dietary changes, in reality celiac disease imparts considerable risks, including reduced bone mineral density, impaired quality of life, and increased overall mortality. In addition, a gluten-free diet is highly burdensome and can profoundly affect patients and their families. For these reasons, care of individuals with celiac disease requires prompt diagnosis and ongoing multidisciplinary management.
MeSH term(s)	Autoantibodies ; Celiac Disease/complications ; Celiac Disease/diagnosis ; Celiac Disease/diet therapy ; Celiac Disease/immunology ; Diet, Gluten-Free ; Female ; Humans ; Immunoglobulin A/analysis ; Middle Aged ; Risk ; Transglutaminases/immunology
Chemical Substances	Autoantibodies ; Immunoglobulin A ; Transglutaminases (EC 2.3.2.13)
Language	English
Publishing date	2011-10-10
Publishing country	United States
Document type	Case Reports ; Clinical Conference ; Journal Article
ZDB-ID	2958-0
ISSN	1538-3598 ; 0254-9077 ; 0002-9955 ; 0098-7484
ISSN (online)	1538-3598
ISSN	0254-9077 ; 0002-9955 ; 0098-7484
DOI	10.1001/jama.306.14.1582
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Article ; Online: A Composite Morphometric Duodenal Biopsy Mucosal Scale for Celiac Disease Encompassing Both Morphology and Inflammation.

Syage, Jack A / Mäki, Markku / Leffler, Daniel A / Silvester, Jocelyn A / Sealey-Voyksner, Jennifer A / Wu, Tsung-Teh / Murray, Joseph A

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2023

Abstract: Background & aims: Villus height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocytes (IEL) are key measures of histology of the small intestine in celiac disease. Although the field of celiac disease has advanced, there remains no broadly ... ...

Abstract	Background & aims: Villus height to crypt depth ratio (Vh:Cd) and intraepithelial lymphocytes (IEL) are key measures of histology of the small intestine in celiac disease. Although the field of celiac disease has advanced, there remains no broadly accepted measure of mucosal injury. We assessed whether a composite Vh:Cd and IEL scale (VCIEL) can improve accuracy and statistical precision for assessing histology, compared with individual measures. Methods: The formulation of the VCIEL composite histologic scale was based on combining the Vh:Cd and IEL measurements for individual patients with equal weighting, by converting each scale to a fraction of their standard deviation and summing the results. The VCIEL formula was applied to several clinical trials and the results for Vh:Cd and IEL were compared with those for VCIEL with regards to clinical significance (effect size) and statistical significance. Results: For the ALV003-1021 trial, we observed an effect size and P value (analysis of covariance) of 1.37 and 0.038 for ΔVh:Cd, 1.17 and 0.005 for ΔIEL, and 1.86 and 0.004 for ΔVCIEL. For the similar gluten-challenge IMGX003-NCCIH-1721 trial, the corresponding results were 0.76 and 0.057 for ΔVh:Cd, 0.98 and 0.018 for ΔIEL, and 1.14 and 0.007 for ΔVCIEL. Similar improvements with the use of VCIEL over individual Vh:Cd and IEL measures were observed for other studies, including a nontherapeutic gluten challenge study. Conclusions: The composite VCIEL scale combining Vh:Cd and IEL values seems to improve accuracy and statistical precision compared with either component alone.
Language	English
Publishing date	2023-11-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2023.10.031
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