Genetic Variations of PTPN2 and PTPN22: Role in the Pathogenesis of Type 1 Diabetes and Crohn's Disease

Increasingly, Johne’s disease of ruminants and human Crohn’s disease are regarded as the same infectious disease: paratuberculosis. Mycobacterium avium ss. paratuberculosis (MAP) is the cause of Johne’s and is the most commonly linked infectious cause of Crohn’s disease. Humans are broadly exposed to MAP in dairy products and in the environment. MAP has been found within granulomas such as Crohn’s disease and can stimulate autoantibodies in diseases such as type 1 diabetes (T1D) and Hashimoto’s thyroiditis. Moreover, beyond Crohn’s and T1D, MAP is increasingly associated with a host of autoimmune diseases. This article suggests near equivalency between paucibacillary Johne’s disease of ruminant animals and human Crohn’s disease and implicates MAP zoonosis beyond Crohn’s disease to include T1D.

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Integrated Enrichment Analysis of Variants and Pathways in Genome-Wide Association Studies Indicates Central Role for IL-2 Signaling Genes in Type 1 Diabetes, and Cytokine Signaling Genes in Crohn's Disease

PLoS Genetics ◽

10.1371/journal.pgen.1003770 ◽

2013 ◽

Vol 9 (10) ◽

pp. e1003770 ◽

Cited By ~ 51

Author(s):

Peter Carbonetto ◽

Matthew Stephens

Keyword(s):

Type 1 Diabetes ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Association Studies ◽

Enrichment Analysis ◽

Genome Wide Association ◽

Cytokine Signaling ◽

Genome Wide Association Studies ◽

Genome Wide

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Crohn’s disease associated CARD15 (NOD2) variants are not involved in the susceptibility to type 1 diabetes

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2005.07.029 ◽

2005 ◽

Vol 86 (3) ◽

pp. 379-383 ◽

Cited By ~ 9

Author(s):

Pegah Ghandil ◽

Claude Chelala ◽

Danièle Dubois-Laforgue ◽

Valérie Senée ◽

Sophie Caillat-Zucman ◽

...

Keyword(s):

Type 1 Diabetes ◽

Crohn’S Disease ◽

Crohn's Disease

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Health Literacy and Quality of Life in Young Adults From The Belgian Crohn's Disease Registry Compared to Type 1 Diabetes Mellitus

Frontiers in Pediatrics ◽

10.3389/fped.2021.624416 ◽

2021 ◽

Vol 9 ◽

Author(s):

Constance Carels ◽

Lucas Wauters ◽

An Outtier ◽

Filip Baert ◽

Peter Bossuyt ◽

...

Keyword(s):

Quality Of Life ◽

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Young Adults ◽

Crohn’S Disease ◽

Health Literacy ◽

Crohn's Disease ◽

Disease Registry

Background and Aims: The management of chronic inflammatory bowel diseases in youth is challenging. We aimed to determine health literacy (HL), quality of life (QoL) and clinical outcomes in young adults from the BELgian CROhn's disease registry (BELCRO) in comparison to type 1 diabetes mellitus (DM) as a control.Methods: In this prospective and observational study, young adults with Crohn's disease (CD) diagnosed < 18 years and with > 5 years disease duration and a comparable group of patients with DM completed validated HL, QoL and work productivity and activity impairment questionnaires (HLS-EU-Q16, EQ-5D-5L and WPAI). HL was scored as sufficient (13–16), problematic (9–12) or inadequate (0–8). QoL was dichotomized into “no problems” (EQ-5D level 1) or “problems” (EQ-5D levels 2 to 5). Non-parametric (Mann-Whitney U) analyses and Spearman correlations were performed.Results: A total of 52 CD (median [IQR] age of 25.0 [23.8-27.0], 64% male) and 50 DM (age 20.0 [19.0-22.0], 50% male) patients were included. HL was 14.0 [11.0-16.0] for CD and 14.0 [11.3-14.8] for DM (p = 0.6) with similar proportions of sufficient (60 vs. 68%, p = 0.4), problematic (34 vs. 26%, p = 0.3) and inadequate HL (both 6%, p = 1). Although QoL was comparable for CD and DM (77.0 [68.8-82.0] vs. 75.0 [65.0-80.0] %, p =0.4), CD had a trend for higher pain/discomfort (50 vs. 32%, p = 0.06). HL and QoL correlated in CD (r = 0.6, p < 0.001) and DM patients (r = 0.6, p < 0.001). Fewer CD patients with recent hospitalization/surgery had sufficient HL (31 vs. 69%, p = 0.01) and had lower QoL (70.0 [60.0-77.0] vs. 80.0 [70.0-85.0], p = 0.04) compared to those without.Conclusions: Selected young Belgian adults suffering from CD for >5 years have similar and sufficient HL compared to DM patients. However, CD patients requiring hospitalization/surgery have lower HL, which indicates the need for targeted educational programs.

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Debaryomyces is enriched in Crohn’s disease intestinal tissue and impairs healing in mice

Science ◽

10.1126/science.abd0919 ◽

2021 ◽

Vol 371 (6534) ◽

pp. 1154-1159 ◽

Cited By ~ 1

Author(s):

Umang Jain ◽

Aaron M. Ver Heul ◽

Shanshan Xiong ◽

Martin H. Gregory ◽

Elora G. Demers ◽

...

Keyword(s):

Crohn’S Disease ◽

Crohn's Disease ◽

Human Subjects ◽

Debaryomyces Hansenii ◽

Myeloid Cell ◽

Mucosal Healing ◽

Mucosal Tissues ◽

Colonic Healing ◽

Gnotobiotic Mice

Alterations of the mycobiota composition associated with Crohn’s disease (CD) are challenging to link to defining elements of pathophysiology, such as poor injury repair. Using culture-dependent and -independent methods, we discovered that Debaryomyces hansenii preferentially localized to and was abundant within incompletely healed intestinal wounds of mice and inflamed mucosal tissues of CD human subjects. D. hansenii cultures from injured mice and inflamed CD tissues impaired colonic healing when introduced into injured conventionally raised or gnotobiotic mice. We reisolated D. hansenii from injured areas of these mice, fulfilling Koch’s postulates. Mechanistically, D. hansenii impaired mucosal healing through the myeloid cell–specific type 1 interferon–CCL5 axis. Taken together, we have identified a fungus that inhabits inflamed CD tissue and can lead to dysregulated mucosal healing.

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Study on Genetic Variance of miR-541 in Type 1 Diabetes

ISRN Endocrinology ◽

10.5402/2012/630861 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 3

Author(s):

Bei Han ◽

Xing Shi ◽

Quan Peng ◽

Wentao Gao

Keyword(s):

Type 1 Diabetes ◽

Healthy Volunteers ◽

Target Genes ◽

Direct Sequencing ◽

Clinical Analysis ◽

Genetic Variations ◽

Luciferase Reporter ◽

Putative Promoter ◽

Putative Promoter Region

Genetic susceptibility plays a key role in type 1 diabetes development. Because miR-541 gene was located within the associated chromosome loci and its target genes include the diabetes-associated gene neurogenin3, this study aimed to investigate whether miR-541 had type 1 diabetes-associated genetic variations. Type 1 diabetes children and healthy volunteers were recruited; direct sequencing was performed in initial 69 patients and 46 volunteers. We identified 1 reported SNP (rs12893725) and 3 novel genetic variations, for the candidate -404 G→T variation, restriction fragment length polymorphism (RFLP) was performed in total 247 diabetes children and 212 healthy volunteers, a different distribution trait of allele frequencies was found between the two groups, and further clinical analysis found no significant correlation between clinical parameter and genotypes among patients. In addition, by luciferase reporter assay, -404 was found to be within putative promoter region of pre-miR-541; although mutation of G→T has no effect on promoter activity, a significant secondary structure alteration may possibly influence its processing and transcription. In conclusion, we identified 3 novel genetic variations in putative promoter of miR-541 in type 1 diabetes patients; -404 G→T of miR-541 is a potential T1D-associated genetic variation.

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Mo1721 CD39 Is a Surface Marker for Type 1 CD8+ T-Cells in Patients With Crohn's Disease

Gastroenterology ◽

10.1016/s0016-5085(14)62338-6 ◽

2014 ◽

Vol 146 (5) ◽

pp. S-644

Author(s):

Aiping Bai ◽

Alan C. Moss ◽

Simon C. Robson

Keyword(s):

T Cells ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Cd8 T Cells ◽

Surface Marker

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The Oxidoreductase DsbA Plays a Key Role in the Ability of the Crohn's Disease-Associated Adherent-Invasive Escherichia coli Strain LF82 To Resist Macrophage Killing

Journal of Bacteriology ◽

10.1128/jb.00233-07 ◽

2007 ◽

Vol 189 (13) ◽

pp. 4860-4871 ◽

Cited By ~ 45

Author(s):

Marie-Agnès Bringer ◽

Nathalie Rolhion ◽

Anne-Lise Glasser ◽

Arlette Darfeuille-Michaud

Keyword(s):

Escherichia Coli ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Epithelial Cells ◽

Intestinal Epithelial Cells ◽

Coli Strain ◽

Intestinal Epithelial ◽

Type 1 Pili ◽

K 12

ABSTRACT Adherent-invasive Escherichia coli (AIEC) isolated from Crohn's disease patients is able to adhere to and invade intestinal epithelial cells and to replicate in mature phagolysosomes within macrophages. Here, we show that the dsbA gene, encoding a periplasmic oxidoreductase, was required for AIEC strain LF82 to adhere to intestinal epithelial cells and to survive within macrophages. The LF82-ΔdsbA mutant did not express flagella and, probably as a consequence of this, did not express type 1 pili. The role of DsbA in adhesion is restricted to the loss of flagella and type 1 pili, as forced contact between bacteria and cells and induced expression of type 1 pili restored the wild-type phenotype. In contrast, the dsbA gene is essential for AIEC LF82 bacteria to survive within macrophages, irrespective of the loss of flagella and type 1 pilus expression, and the survival ability of LF82-ΔdsbA was as low as that of the nonpathogenic E. coli K-12, which was efficiently killed by macrophages. We also provide evidence that the dsbA gene is needed for LF82 bacteria to grow and survive in an acidic and nutrient-poor medium that partly mimics the harsh environment of the phagocytic vacuole. In addition, under such stress conditions dsbA transcription is highly up-regulated. Finally, the CpxRA signaling pathway does not play a role in regulation of dsbA expression in AIEC LF82 bacteria under conditions similar to those of mature phagolysosomes.

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