Skip to main content

Advertisement

SpringerLink
Log in

Local Pentraxin-2 Deficit Is a Feature of Intestinal Fibrosis in Crohn’s Disease

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Pentraxin-2 (PTX-2) is a homo-pentameric plasma protein showing evidence of antifibrotic activity in Phase 2 clinical trials in idiopathic pulmonary fibrosis (IPF). Whether PTX-2 plays a role in other fibrotic diseases, including intestinal fibrosis which commonly occurs in inflammatory bowel disease (IBD), remains unknown.

Aims

This study aimed to qualitatively and quantitatively assess PTX-2 expression in fibrostenotic Crohn’s disease (FCD) and determine whether expression is correlated with postsurgical restenosis.

Methods

Immunohistochemistry was performed in histologic sections of small bowel resected from patients with fibrostenotic Crohn’s disease (FCD), comparing strictured segments with adjacent surgical margins from the same patient. Ileal resections from patients without inflammatory bowel disease were examined as controls.

Results

PTX-2 signal was analyzed in 18 patients with FCD and 15 patients without IBD and localized predominantly to submucosal vasculature, including arterial subendothelium and internal elastic lamina, and perivascular connective tissue. PTX-2 signal in the surgical margins from patients with FCD strictures (where tissue architecture was normal) was consistently lower than non-IBD samples. Fibrostenotic regions showed increased PTX-2 signal relative to surgical margins from the same patient in 14/15 paired samples. Submucosal/mural PTX-2 signal in fibrostenotic tissue was lower in patients who subsequently experienced re-stenosis (P = 0.015).

Conclusions

This exploratory study is the first analysis of PTX-2 within the intestine, and demonstrates that PTX-2 signal is reduced in the architecturally normal bowel of patients with FCD. Lower submucosal PTX-2 levels in patients with re-stenosis raises the possibility of a protective role of PTX-2 in intestinal fibrosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Cosnes J, Cattan S, Blain A et al. Long-term evolution of disease behavior of Crohn’s disease. Inflamm Bowel Dis 2002;8:244–250.

    Article  PubMed  Google Scholar 

  2. Rieder F, Fiocchi C, Rogler G. Mechanisms, management, and treatment of fibrosis in patients with inflammatory bowel diseases. Gastroenterology 2017;152:340-350.e6.

    Article  PubMed  Google Scholar 

  3. Latella G, Di Gregorio J, Flati V et al. Mechanisms of initiation and progression of intestinal fibrosis in IBD. Scand J Gastroenterol 2015;50:53–65.

    Article  CAS  PubMed  Google Scholar 

  4. Louis E, Collard A, Oger AF et al. Behaviour of Crohn’s disease according to the Vienna classification: changing pattern over the course of the disease. Gut 2001;49:777–782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Nakagawa N, Barron L, Gomez IG et al. Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease. JCI Insight 2016;1:e87446.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Lu J, Marnell LL, Marjon KD et al. Structural recognition and functional activation of FcgammaR by innate pentraxins. Nature 2008;456:989–992.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Pilling D, Gomer RH. The development of serum amyloid P as a possible therapeutic. Front Immunol 2018;9:2328.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cox N, Pilling D, Gomer RH. Distinct Fcγ receptors mediate the effect of serum amyloid p on neutrophil adhesion and fibrocyte differentiation. J Immunol 2014;193:1701–1708.

    Article  CAS  PubMed  Google Scholar 

  9. Raghu G, van den Blink B, Hamblin MJ et al. Long-term treatment with recombinant human pentraxin 2 protein in patients with idiopathic pulmonary fibrosis: an open-label extension study. Lancet Respir Med 2019;7:657–664.

    Article  CAS  PubMed  Google Scholar 

  10. Basturk T, Ojalvo D, Mazi EE et al. Pentraxin-2 is associated with renal fibrosis in patients undergoing renal biopsy. Clinics 2020;75:e1809.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Hutchinson WL, Hohenester E, Pepys MB. Human serum amyloid P component is a single uncomplexed pentamer in whole serum. Mol Med 2000;6:482–493.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Allez M, Auzolle C, Ngollo M et al. T cell clonal expansions in ileal Crohn’s disease are associated with smoking behaviour and postoperative recurrence. Gut 2019;68:1961–1970.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We gratefully acknowledge the following: Jason Low and KT Park for critical manuscript review; Rhian Jacob-Moffatt for critical statistical methodology review.

Funding

Financial support for this project was provided by Genentech Inc, South San Francisco, CA, USA. Authors FVP, JM, and MN are full-time employees of Genentech Inc and are stockholders in Roche Holding AG, Basel, Switzerland.

Author information

Authors and Affiliations

  1. Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Stanford University, 750 Welch Rd Ste 116, Palo Alto, CA, 94304, USA

    Steven Levitte

  2. Research Pathology, Genentech Inc., South San Francisco, CA, USA

    Franklin V. Peale

  3. Department of Pathology, Stanford University, Palo Alto, CA, USA

    Iny Jhun

  4. OMNI Biomarker Development, Genentech Inc., South San Francisco, CA, USA

    Jacqueline McBride & Margaret Neighbors

Authors
  1. Steven Levitte
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Franklin V. Peale
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Iny Jhun
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jacqueline McBride
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Margaret Neighbors
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Project conceptualization (SL, IJ, MN), data curation (SL, FP, IJ, MN), methodologies (SL, FP, IJ, JM, MN), formal analysis (SL, FP, IJ, MN), original draft of manuscript (SL), editing and final approval of manuscript (all authors).

Corresponding author

Correspondence to Steven Levitte.

Ethics declarations

Conflict of interest

The authors report no relevant conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Levitte, S., Peale, F.V., Jhun, I. et al. Local Pentraxin-2 Deficit Is a Feature of Intestinal Fibrosis in Crohn’s Disease. Dig Dis Sci 68, 2975–2980 (2023). https://doi.org/10.1007/s10620-023-07909-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-023-07909-1

Keywords

Search

Navigation