Tue Bjerg Bennike, Kate Templeton1, Kimino Fujimura2, Melena D Bellin, Saima Ahmed3, Christoph N Schlaffner, Rohit Arora4, Zobeida Cruz-Monserrate5, Ramy Arnaout4, Gregory J Beilman6, Amit S Grover, Darwin L Conwell5, Hanno Steen3. 1. Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital. 2. F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA. 3. From the Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA. 4. Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA. 5. Division of Gastroenterology, Hepatology and Nutrition, Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH. 6. Department of Surgery, University of Minnesota Medical School, Minneapolis, MN.
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.
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.
Authors: Jorge D Machicado; Stephen T Amann; Michelle A Anderson; Judah Abberbock; Stuart Sherman; Darwin L Conwell; Gregory A Cote; Vikesh K Singh; Michele D Lewis; Samer Alkaade; Bimaljit S Sandhu; Nalini M Guda; Thiruvengadam Muniraj; Gong Tang; John Baillie; Randall E Brand; Timothy B Gardner; Andres Gelrud; Christopher E Forsmark; Peter A Banks; Adam Slivka; C Mel Wilcox; David C Whitcomb; Dhiraj Yadav Journal: Am J Gastroenterol Date: 2017-02-28 Impact factor: 10.864
Authors: Djuna L Cahen; Dirk J Gouma; Yung Nio; Erik A J Rauws; Marja A Boermeester; Olivier R Busch; Jaap Stoker; Johan S Laméris; Marcel G W Dijkgraaf; Kees Huibregtse; Marco J Bruno Journal: N Engl J Med Date: 2007-02-15 Impact factor: 91.245
Authors: Andrzej Lewandowicz; Magdalena Bakun; Rafał Kohutnicki; Agnieszka Fabijańska; Michał Kistowski; Jacek Imiela; Michał Dadlez Journal: Pol Arch Med Wewn Date: 2015-01-12
Authors: Jorg Kleeff; David C Whitcomb; Tooru Shimosegawa; Irene Esposito; Markus M Lerch; Thomas Gress; Julia Mayerle; Asbjørn Mohr Drewes; Vinciane Rebours; Fatih Akisik; J Enrique Domínguez Muñoz; John P Neoptolemos Journal: Nat Rev Dis Primers Date: 2017-09-07 Impact factor: 52.329
Authors: Tue Bennike; Ugur Ayturk; Carla M Haslauer; John W Froehlich; Benedikt L Proffen; Omar Barnaby; Svend Birkelund; Martha M Murray; Matthew L Warman; Allan Stensballe; Hanno Steen Journal: J Proteome Res Date: 2014-09-03 Impact factor: 4.466