Urine Proteomics Reveals Sex-Specific Response to Total Pancreatectomy With Islet Autotransplantation

Tue Bjerg Bennike, Kate Templeton, Kimino Fujimura, Melena D. Bellin, Saima Ahmed, Christoph N. Schlaffner, Rohit Arora, Zobeida Cruz-Monserrate, Ramy Arnaout, Gregory J. Beilman, Amit S. Grover, Darwin L. Conwell, Hanno Steen

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical option for refractory chronic pancreatitis-related pain. Despite the known clinical implications of TPIAT, the molecular effects remain poorly investigated. We performed the first hypothesis-generating study of the urinary proteome before and after TPIAT. Methods Twenty-two patients eligible for TPIAT were prospectively enrolled. Urine samples were collected the week before and 12 to 18 months after TPIAT. The urine samples were prepared for bottom-up label-free quantitative proteomics using the "MStern"protocol. Results Using 17 paired samples, we identified 2477 urinary proteins, of which 301 were significantly changed post-TPIAT versus pre-TPIAT. Our quantitative analysis revealed that the molecular response to TPIAT was highly sex-specific, with pronounced sex differences pre-TPIAT but minimal differences afterward. Comparing post-TPIAT versus pre-TPIAT, we found changes in cell-cell adhesion, intracellular vacuoles, and immune response proteins. After surgery, immunoglobulins, complement proteins, and cathepsins were increased, findings that may reflect glomerular damage. Finally, we identified both known and novel markers for immunoglobulin A nephropathy after 1 patient developed the disease 2 years after TPIAT. Conclusions We found distinct changes in the urinary proteomic profile after TPIAT and the response to TPIAT is highly sex-specific.

Original languageEnglish (US)
Pages (from-to)435-444
Number of pages10
JournalPancreas
Volume51
Issue number5
DOIs
StatePublished - May 1 2022

Bibliographical note

Funding Information:
T.B. was supported by the Lundbeck Foundation, the Carlsberg Foundation, and A.P. Møller Foundation. K.F. was supported by Overseas Research Fellowship Grant from the Japan Society for the Promotion of Science.

Funding Information:
This study was supported by the National Cancer Institute and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) under award numbers related to The Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC): U01DK126300 (M.D.B and G.J.B.) and U01DK108327 (H.S. and D.C.).

Publisher Copyright:
© Wolters Kluwer Health, Inc. All rights reserved.

Keywords

  • TPIAT
  • autoislet
  • diabetes
  • nephropathy
  • pancreatectomy
  • pancreatitis

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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