Proteomic analysis-based discovery of a novel biomarker that differentiates intestinal Behçet’s disease from Crohn’s disease

Park, Jihye; Jeong, Da-Eun; Chung, Youn Wook; Han, Seunghan; Kim, Da Hye; Yu, Jongwook; Cheon, Jae Hee; Ryu, Ji Hwan

doi:10.1038/s41598-021-90250-2

Cited by 6 publications

(6 citation statements)

References 46 publications

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“…Both herpesvirus and hemoplasma infections also shared MGAM as a putative biomarker, but this protein was a positive predictor for these viruses and a negative predictor for these bacteria. MGAM is involved in breaking down carbohydrates in the small intestine, and its deficiency has been linked to gastrointestinal diseases ( 76 , 77 ). Although MGAM seems to have a role in neutrophil biology ( 78 ) and may have a role in regulating inflammatory responses in the gastrointestinal tract, which contains the largest population of mast cells in the body ( 79 ), little is known about its immune function, and our results highlight a potential distinction between viral and bacterial infections.…”

Section: Discussionmentioning

confidence: 99%

Serum proteomics reveals a tolerant immune phenotype across multiple pathogen taxa in wild vampire bats

Vicente-Santos,

Lock,

Allira

et al. 2023

Front. Immunol.

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Bats carry many zoonotic pathogens without showing pronounced pathology, with a few exceptions. The underlying immune tolerance mechanisms in bats remain poorly understood, although information-rich omics tools hold promise for identifying a wide range of immune markers and their relationship with infection. To evaluate the generality of immune responses to infection, we assessed the differences and similarities in serum proteomes of wild vampire bats (Desmodus rotundus) across infection status with five taxonomically distinct pathogens: bacteria (Bartonella spp., hemoplasmas), protozoa (Trypanosoma cruzi), and DNA (herpesviruses) and RNA (alphacoronaviruses) viruses. From 19 bats sampled in 2019 in Belize, we evaluated the up- and downregulated immune responses of infected versus uninfected individuals for each pathogen. Using a high-quality genome annotation for vampire bats, we identified 586 serum proteins but found no evidence for differential abundance nor differences in composition between infected and uninfected bats. However, using receiver operating characteristic curves, we identified four to 48 candidate biomarkers of infection depending on the pathogen, including seven overlapping biomarkers (DSG2, PCBP1, MGAM, APOA4, DPEP1, GOT1, and IGFALS). Enrichment analysis of these proteins revealed that our viral pathogens, but not the bacteria or protozoa studied, were associated with upregulation of extracellular and cytoplasmatic secretory vesicles (indicative of viral replication) and downregulation of complement activation and coagulation cascades. Additionally, herpesvirus infection elicited a downregulation of leukocyte-mediated immunity and defense response but an upregulation of an inflammatory and humoral immune response. In contrast to our two viral infections, we found downregulation of lipid and cholesterol homeostasis and metabolism with Bartonella spp. infection, of platelet-dense and secretory granules with hemoplasma infection, and of blood coagulation pathways with T. cruzi infection. Despite the small sample size, our results suggest that vampire bats have a similar suite of immune mechanisms for viruses distinct from responses to the other pathogen taxa, and we identify potential biomarkers that can expand our understanding of pathogenesis of these infections in bats. By applying a proteomic approach to a multi-pathogen system in wild animals, our study provides a distinct framework that could be expanded across bat species to increase our understanding of how bats tolerate pathogens.

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Section: Discussionmentioning

confidence: 99%

Serum proteomics reveals a tolerant immune phenotype across multiple pathogen taxa in wild vampire bats

Vicente-Santos,

Lock,

Allira

et al. 2023

Front. Immunol.

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“…In human medicine, the discovery of proteomic biomarkers is a multi‐phase process where the initial phase involves screening for potential protein biomarkers with a small number of samples using mass spectrometry techniques, followed by verification of the markers using alternative techniques and increased number of samples. A validation phase then tracks the successful (single) biomarker candidate(s) within a large sample cohort 58,59 . The higher numbers of IBD cases in our cohort of dogs might reflect referral of cases that were more challenging to manage and required biopsies.…”

Section: Discussionmentioning

confidence: 99%

“…A validation phase then tracks the successful (single) biomarker candidate(s) within a large sample cohort. 58 , 59 The higher numbers of IBD cases in our cohort of dogs might reflect referral of cases that were more challenging to manage and required biopsies. Each case was managed at the discretion of the attending veterinarian and the case management was not standardized.…”

Section: Discussionmentioning

confidence: 99%

Serum proteome of dogs with chronic enteropathy

Ruaux

Griebsch

et al. 2023

Veterinary Internal Medicne

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Background: Chronic enteropathy (CE) is common in dogs and can occur with multiple etiologies including food-responsive enteropathy (FRE) and idiopathic inflammatory bowel disease (IBD).Hypothesis/Objective: To study the protein profile and pathway differences among dogs with FRE, IBD, and healthy controls using serum proteome analysis.Animals: Nine CE dogs with signs of gastrointestinal disease and histologically confirmed chronic inflammatory enteropathy and 16 healthy controls. Methods:A cross-sectional study with cases recruited from 2 veterinary hospitals between May 2019 and November 2020 was performed. Serum samples were analyzed using mass spectrometry-based proteomic techniques.Results: Proteomic profiles showed marked variation in relative protein abundances.Forty-five proteins were significantly (P ≤ .01) differentially expressed among the dogs with CE and controls with ≥2-fold change in abundance. The fold change of dogs with IBD normalized to controls was more pronounced for the majority of proteins than that seen in the dogs with FRE normalized to control dogs. Proteins involving reactive oxygen species, cytokine activation, acute phase response signaling, and lipid metabolism were altered in dogs with CE.Conclusions and Clinical Importance: Cytokine alterations, acute phase response signaling, and lipid metabolism are likely involved in pathogenesis of CE. Although there are insufficient current data to justify the use of proteomic biomarkers for assessment of CE in dogs, our study identifies potential candidates.

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“…Given the extensive use of serum protein profiles in IBD in human medicine and studies in other areas of small animal medicine, serum proteomics might provide useful biomarkers in cats with CE 8,14 . The discovery of new proteomic biomarkers is a multi‐phase process which involves screening for potential biomarkers using an untargeted approach with a small sample size at the discovery phase followed by verification of selected proteins using targeted approaches with a larger sample size at the validation phase 20,21 . A recent study investigated the intestinal mucosal proteome in cats with 9 proteins found to be differentially expressed between healthy cats and cats with IBD and LGAL 22 .…”

Section: Introductionmentioning

confidence: 99%

“… 8 , 14 The discovery of new proteomic biomarkers is a multi‐phase process which involves screening for potential biomarkers using an untargeted approach with a small sample size at the discovery phase followed by verification of selected proteins using targeted approaches with a larger sample size at the validation phase. 20 , 21 A recent study investigated the intestinal mucosal proteome in cats with 9 proteins found to be differentially expressed between healthy cats and cats with IBD and LGAL. 22 However, western blot analysis did not confirm significant differential protein expression.…”

Section: Introductionmentioning

confidence: 99%

Serum proteome profiles in cats with chronic enteropathies

Yu,

Boland,

Catt

et al. 2023

Veterinary Internal Medicne

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Background: Serum protein biomarkers are used to diagnose, monitor treatment response, and to differentiate various forms of chronic enteropathies (CE) in humans.The utility of liquid biopsy proteomic approaches has not been examined in cats.Hypothesis/Objectives: To explore the serum proteome in cats to identify markers differentiating healthy cats from cats with CE.Animals: Ten cats with CE with signs of gastrointestinal disease of at least 3 weeks duration, and biopsy-confirmed diagnoses, with or without treatment and 19 healthy cats were included.Methods: Cross-sectional, multicenter, exploratory study with cases recruited from 3 veterinary hospitals between May 2019 and November 2020. Serum samples were analyzed and evaluated using mass spectrometry-based proteomic techniques.Results: Twenty-six proteins were significantly (P < .02, ≥5-fold change in abundance) differentially expressed between cats with CE and controls. Thrombospondin-1 (THBS1) was identified with >50-fold increase in abundance in cats with CE (P < 0.001) compared to healthy cats.Conclusions and Clinical Importance: Damage to the gut lining released marker proteins of chronic inflammation that were detectable in serum samples of cats. This early-stage exploratory study strongly supports THBS1 as a candidate biomarker for chronic inflammatory enteropathy in cats.

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Proteomic analysis-based discovery of a novel biomarker that differentiates intestinal Behçet’s disease from Crohn’s disease

Cited by 6 publications

References 46 publications

Serum proteomics reveals a tolerant immune phenotype across multiple pathogen taxa in wild vampire bats

Serum proteomics reveals a tolerant immune phenotype across multiple pathogen taxa in wild vampire bats

Serum proteome of dogs with chronic enteropathy

Serum proteome profiles in cats with chronic enteropathies

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