Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research Article
  • Published:

In situ mass spectrometry of autoimmune liver diseases

Cellular & Molecular Immunology volume 8, pages 237–242 (2011)Cite this article

Abstract

Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) are the major forms of autoimmune liver diseases each characterized by the destruction of a specific liver cell type and the presence of differing auto-antibodies. We took a proteomic approach utilizing in situ matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) to obtain profiles directly from liver samples of patients with PBC, PSC, AIH and controls. The ability to precisely localize the region for acquisition of MALDI MS allowed us to obtain profiles from bile ducts, inflammatory infiltrates and hepatocytes from each biopsy sample. Analysis tools developed to identify peaks and compare peaks across diseases and cell types were used to develop models to classify the samples. Using an initial set of testing samples from PBC patients and controls, we identified unique peaks present in bile ducts, inflammatory infiltrates and hepatocytes that could classify samples in a validation cohort with 88–91% accuracy. Interestingly, profiles of PSC and AIH did not differ significantly from PBC. Identification of proteins in these peaks may represent novel autoantigens or effector molecules. These findings illustrate the potential of a proteomic approach to autoimmune diseases with in situ MALDI MS.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Selmi C, Meda F, Kasangian A, Invernizzi P, Tian Z, Lian Z et al. Experimental evidence on the immunopathogenesis of primary biliary cirrhosis. Cell Mol Immunol 2010; 7: 1–10.

    Article  PubMed  Google Scholar 

  2. Aron JH, Bowlus CL . The immunobiology of primary sclerosing cholangitis. Semin Immunopathol 2009; 31: 383–397.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Ichiki Y, Aoki CA, Bowlus CL, Shimoda S, Ishibashi H, Gershwin ME . T cell immunity in autoimmune hepatitis. Autoimmun Rev 2005; 4: 315–321.

    Article  CAS  PubMed  Google Scholar 

  4. Moritoki Y, Lian ZX, Ohsugi Y, Ueno Y, Gershwin ME . B cells and autoimmune liver diseases. Autoimmun Rev 2006; 5: 449–457.

    Article  CAS  PubMed  Google Scholar 

  5. Yanagisawa K, Shyr Y, Xu BJ, Massion PP, Larsen PH, White BC et al. Proteomic patterns of tumour subsets in non-small-cell lung cancer. Lancet 2003; 362: 433–439.

    Article  CAS  PubMed  Google Scholar 

  6. Chaurand P, Norris JL, Cornett DS, Mobley JA, Caprioli RM . New developments in profiling and imaging of proteins from tissue sections by MALDI mass spectrometry. J Proteome Res 2006; 5: 2889–2900.

    Article  CAS  PubMed  Google Scholar 

  7. Cornett DS, Mobley JA, Dias EC, Andersson M, Arteaga CL, Sanders ME et al. A novel histology-directed strategy for MALDI-MS tissue profiling that improves throughput and cellular specificity in human breast cancer. Mol Cell Proteomics 2006; 5: 1975–1983.

    Article  CAS  PubMed  Google Scholar 

  8. Amann JM, Chaurand P, Gonzalez A, Mobley JA, Massion PP, Carbone DP et al. Selective profiling of proteins in lung cancer cells from fine-needle aspirates by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Clin Cancer Res 2006; 12: 5142–5150.

    Article  CAS  PubMed  Google Scholar 

  9. Chaurand P, Cornett DS, Caprioli RM . Molecular imaging of thin mammalian tissue sections by mass spectrometry. Curr Opin Biotechnol 2006; 17: 431–436.

    Article  CAS  PubMed  Google Scholar 

  10. Sanders ME, Dias EC, Xu BJ, Mobley JA, Billheimer D, Roder H et al. Differentiating proteomic biomarkers in breast cancer by laser capture microdissection and MALDI MS. J Proteome Res 2008; 7: 1500–1507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Theodoridis S, Koutroumbas K . Pattern recognition. Boston: Elsevier/Academic Press, 2006.

    Chapter  Google Scholar 

  12. Webb AR . Statistical pattern recognition. New Jersey: Wiley, 2002.

  13. Honda M, Kawai H, Shirota Y, Yamashita T, Kaneko S . Differential gene expression profiles in stage I primary biliary cirrhosis. Am J Gastroenterol 2005; 100: 2019–2030.

    Article  CAS  PubMed  Google Scholar 

  14. Aoki CA, Dawson K, Kenny TP, Gershwin ME, Bowlus CL . Gene expression by PBMC in primary sclerosing cholangitis: evidence for dysregulation of immune mediated genes. Clin Dev Immunol 2006; 13: 265–271.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chen L, Borozan I, Milkiewicz P, Sun J, Meng X, Coltescu C et al. Gene expression profiling of early primary biliary cirrhosis: possible insights into the mechanism of action of ursodeoxycholic acid. Liver Int 2008; 28: 997–1010.

    Article  CAS  PubMed  Google Scholar 

  16. Furuta K, Sato S, Yamauchi T, Ozawa T, Harada M, Kakumu S . Intrahepatic gene expression profiles in chronic hepatitis B and autoimmune liver disease. J Gastroenterol 2008; 43: 866–874.

    Article  CAS  PubMed  Google Scholar 

  17. Padgett KA, Lan RY, Leung PC, Lleo A, Dawson K, Pfeiff J et al. Primary biliary cirrhosis is associated with altered hepatic microRNA expression. J Autoimmun 2009; 32: 246–253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Anderson L, Seilhamer J . A comparison of selected mRNA and protein abundances in human liver. Electrophoresis 1997; 18: 533–537.

    Article  CAS  PubMed  Google Scholar 

  19. Oertelt S, Rieger R, Selmi C, Invernizzi P, Ansari AA, Coppel RL et al. A sensitive bead assay for antimitochondrial antibodies: chipping away at AMA-negative primary biliary cirrhosis. Hepatology 2007; 45: 659–665.

    Article  CAS  PubMed  Google Scholar 

  20. Bauer JA, Chakravarthy AB, Rosenbluth JM, Mi D, Seeley EH, de Matos Granja-Ingram N et al. Identification of markers of taxane sensitivity using proteomic and genomic analyses of breast tumors from patients receiving neoadjuvant paclitaxel and radiation. Clin Cancer Res 2010; 16: 681–690.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by NIH/NIGMS 5R01 GM58008, Vanderbilt Ingram Cancer Center Core Support Grant P30 CA068485, NIH DK39588 and National Foundation for Cancer Research: Vanderbilt Center for Proteomics and Drug Action.

Author information

Author notes

  1. Dr CL Bowlus, 4150 V Street, PSSB 3500, Sacramento, CA 95817, USA. E-mail: clbowlus@ucdavis.edu

Authors and Affiliations

  1. Division of Gastroenterology and Hepatology, University of California, Davis, CA, USA

    Christopher L Bowlus

  2. Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, TN, USA

    Erin H Seeley & Richard M Caprioli

  3. Biodesix, Steamboat Springs, CO, USA

    Joanna Roder, Julia Grigorieva & Heinrich Roder

  4. Division of Clinical Immunology, Allergy and Rheumatology, University of California, Davis, CA, USA

    MEric Gershwin

Authors
  1. Christopher L Bowlus
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Erin H Seeley
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joanna Roder
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Julia Grigorieva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Heinrich Roder
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Richard M Caprioli
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. MEric Gershwin
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bowlus, C., Seeley, E., Roder, J. et al. In situ mass spectrometry of autoimmune liver diseases. Cell Mol Immunol 8, 237–242 (2011). https://doi.org/10.1038/cmi.2010.72

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/cmi.2010.72

Keywords

This article is cited by

Search

Advanced search

Quick links