Skip to main content
Top
Published in: Clinical Rheumatology 12/2014

01-12-2014 | Original Article

Establishment of a novel diagnostic model for Sjögren’s syndrome by proteomic fingerprinting

Authors: Yuhui Li, Xiaolin Sun, Xuewu Zhang, Yuqin Yang, Rulin Jia, Xu Liu, Ru Li, Yanying Liu, Zhanguo Li

Published in: Clinical Rheumatology | Issue 12/2014

Login to get access

Abstract

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease that lacks sensitive and specific diagnostic methods. The aim of this study was to identify potential biomarkers specific for pSS and to establish a diagnostic model. Serum samples from patients with pSS, disease controls (DC, patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA)), and healthy controls (HC)) were randomly divided into a training set (35 pSS, 50 DC, and 26 HC) and a testing set (25 pSS, 50 DC, and 25 HC). Weak cationic exchange (WCX) magnetic beads were used to differentially capture serum proteins prior to proteomic analysis. Proteomic mass spectra were generated by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). One hundred differential M/Z peaks associated with pSS were identified, and the m/z peaks at 8,133.85, 11,972.8, 2,220.81, and 4,837.66 were used to establish a diagnostic model for pSS. This diagnostic model was able to distinguish pSS from non-pSS controls with a sensitivity of 77.1 % and a specificity of 85.5 %, and its efficacy was confirmed in our blinded testing set with good sensitivity and specificity of 95.5 and 88 %, respectively. The results indicated that the proteomic fingerprinting model was effective in the diagnosis of pSS.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ioannidis JP, Vassiliou VA, Moutsopoulos HM (2002) Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjögren’s syndrome. Arthritis Rheum 46(3):741–7PubMedCrossRef Ioannidis JP, Vassiliou VA, Moutsopoulos HM (2002) Long-term risk of mortality and lymphoproliferative disease and predictive classification of primary Sjögren’s syndrome. Arthritis Rheum 46(3):741–7PubMedCrossRef
2.
go back to reference Skopouli FN, Dafni U, Ioannidis JP, Moutsopoulos HM (2000) Clinical evolution, and morbidity and mortality of primary Sjögren’s syndrome. Semin Arthritis Rheum 29(5):296–304PubMedCrossRef Skopouli FN, Dafni U, Ioannidis JP, Moutsopoulos HM (2000) Clinical evolution, and morbidity and mortality of primary Sjögren’s syndrome. Semin Arthritis Rheum 29(5):296–304PubMedCrossRef
3.
go back to reference Theander E, Manthorpe R, Jacobsson LT (2004) Mortality and causes of death in primary Sjögren’s syndrome: a prospective cohort study. Arthritis Rheum 50(4):1262–9PubMedCrossRef Theander E, Manthorpe R, Jacobsson LT (2004) Mortality and causes of death in primary Sjögren’s syndrome: a prospective cohort study. Arthritis Rheum 50(4):1262–9PubMedCrossRef
4.
go back to reference Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH, European Study Group on Classification Criteria for Sjögren’s Syndrome (2002) Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61(6):554–8PubMedCentralPubMedCrossRef Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH, European Study Group on Classification Criteria for Sjögren’s Syndrome (2002) Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61(6):554–8PubMedCentralPubMedCrossRef
5.
go back to reference Shiboski SC, Shiboski CH, Criswell L, Baer A, Challacombe S, Lanfranchi H, Schiødt M, Umehara H, Vivino F, Zhao Y, Dong Y, Greenspan D, Heidenreich AM, Helin P, Kirkham B, Kitagawa K, Larkin G, Li M, Lietman T, Lindegaard J, McNamara N, Sack K, Shirlaw P, Sugai S, Vollenweider C, Whitcher J, Wu A, Zhang S, Zhang W, Greenspan J, Daniels T, Sjögren’s International Collaborative Clinical Alliance (SICCA) Research Groups (2012) American college of rheumatology classification criteria for Sjögren’s syndrome: a data-driven, expert consensus approach in the Sjögren’s international collaborative clinical alliance cohort. Arthritis Care Res (Hoboken) 64(4):475–87CrossRef Shiboski SC, Shiboski CH, Criswell L, Baer A, Challacombe S, Lanfranchi H, Schiødt M, Umehara H, Vivino F, Zhao Y, Dong Y, Greenspan D, Heidenreich AM, Helin P, Kirkham B, Kitagawa K, Larkin G, Li M, Lietman T, Lindegaard J, McNamara N, Sack K, Shirlaw P, Sugai S, Vollenweider C, Whitcher J, Wu A, Zhang S, Zhang W, Greenspan J, Daniels T, Sjögren’s International Collaborative Clinical Alliance (SICCA) Research Groups (2012) American college of rheumatology classification criteria for Sjögren’s syndrome: a data-driven, expert consensus approach in the Sjögren’s international collaborative clinical alliance cohort. Arthritis Care Res (Hoboken) 64(4):475–87CrossRef
8.
go back to reference de Noo ME, Mertens BJ, Ozalp A, Bladergroen MR, van der Werff MP, van de Velde CJ, Deelder AM, Tollenaar RA (2006) Detection of colorectal cancer using MALDI-TOF serum protein profiling. Eur J Cancer 42(8):1068–1076PubMedCrossRef de Noo ME, Mertens BJ, Ozalp A, Bladergroen MR, van der Werff MP, van de Velde CJ, Deelder AM, Tollenaar RA (2006) Detection of colorectal cancer using MALDI-TOF serum protein profiling. Eur J Cancer 42(8):1068–1076PubMedCrossRef
9.
go back to reference Cheng AJ, Chen LC, Chien KY, Chen YJ, Chang JT, Wang HM, Liao CT, Chen IH (2005) Oral cancer plasma tumor marker identified with bead-based affinity-fractionated proteomic technology. Clin Chem 51(12):2236–44PubMedCrossRef Cheng AJ, Chen LC, Chien KY, Chen YJ, Chang JT, Wang HM, Liao CT, Chen IH (2005) Oral cancer plasma tumor marker identified with bead-based affinity-fractionated proteomic technology. Clin Chem 51(12):2236–44PubMedCrossRef
10.
go back to reference Peter JF, Otto AM, Wolf B (2007) Enrichment and detection of molecules secreted by tumor cells using magnetic reversed-phase particle and LC-MALDI-TOF-MS. J Biomol Tech 18(5):287–297PubMedCentralPubMed Peter JF, Otto AM, Wolf B (2007) Enrichment and detection of molecules secreted by tumor cells using magnetic reversed-phase particle and LC-MALDI-TOF-MS. J Biomol Tech 18(5):287–297PubMedCentralPubMed
11.
12.
go back to reference Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM, Mills GB, Simone C, Fishman DA, Kohn EC, Liotta LA (2002) Use of proteomic patterns in serum to identify ovarian cancer. Lancet 359(9306):572–7PubMedCrossRef Petricoin EF, Ardekani AM, Hitt BA, Levine PJ, Fusaro VA, Steinberg SM, Mills GB, Simone C, Fishman DA, Kohn EC, Liotta LA (2002) Use of proteomic patterns in serum to identify ovarian cancer. Lancet 359(9306):572–7PubMedCrossRef
13.
go back to reference Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. J Ann Rheum Dis 69(9):1580–1588CrossRef Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD, Combe B, Costenbader KH, Dougados M, Emery P, Ferraccioli G, Hazes JM, Hobbs K, Huizinga TW, Kavanaugh A, Kay J, Kvien TK, Laing T, Mease P, Ménard HA, Moreland LW, Naden RL, Pincus T, Smolen JS, Stanislawska-Biernat E, Symmons D, Tak PP, Upchurch KS, Vencovsky J, Wolfe F, Hawker G (2010) 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. J Ann Rheum Dis 69(9):1580–1588CrossRef
14.
go back to reference Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):p. 1725CrossRef Hochberg MC (1997) Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 40(9):p. 1725CrossRef
15.
go back to reference Freed GL, Cazares LH, Fichandler CE, Fuller TW, Sawyer CA, Stack BC Jr, Schraff S, Semmes OJ, Wadsworth JT, Drake RR (2008) Differential capture of serum proteins for expression profiling and biomarker discovery in pre- and post-treatment head and neck cancer samples. Laryngoscope 118(1):61–8PubMedCrossRef Freed GL, Cazares LH, Fichandler CE, Fuller TW, Sawyer CA, Stack BC Jr, Schraff S, Semmes OJ, Wadsworth JT, Drake RR (2008) Differential capture of serum proteins for expression profiling and biomarker discovery in pre- and post-treatment head and neck cancer samples. Laryngoscope 118(1):61–8PubMedCrossRef
16.
go back to reference Bañez LL, Prasanna P, Sun L, Ali A, Zou Z, Adam BL, McLeod DG, Moul JW, Srivastava S (2003) Diagnostic potential of serum proteomic patterns in prostate cancer. J Urol 170(2 pt 1):442–6PubMedCrossRef Bañez LL, Prasanna P, Sun L, Ali A, Zou Z, Adam BL, McLeod DG, Moul JW, Srivastava S (2003) Diagnostic potential of serum proteomic patterns in prostate cancer. J Urol 170(2 pt 1):442–6PubMedCrossRef
17.
go back to reference Beeley JA, Khoo KS (1999) Salivary proteins in rheumatoid arthritis and Sjögren’s syndrome: one-dimensional and two-dimensional electrophoretic studies. Electrophoresis 20(7):1652–1660PubMedCrossRef Beeley JA, Khoo KS (1999) Salivary proteins in rheumatoid arthritis and Sjögren’s syndrome: one-dimensional and two-dimensional electrophoretic studies. Electrophoresis 20(7):1652–1660PubMedCrossRef
18.
go back to reference Tomosugi N, Kitagawa K, Takahashi N, Sugai S, Ishikawa I (2005) Diagnostic potential of tear proteomic patterns in Sjögren’s syndrome. J Proteome Res 4(3):820–825PubMedCrossRef Tomosugi N, Kitagawa K, Takahashi N, Sugai S, Ishikawa I (2005) Diagnostic potential of tear proteomic patterns in Sjögren’s syndrome. J Proteome Res 4(3):820–825PubMedCrossRef
19.
go back to reference Ryu OH, Arkinson JC, Hoehn GT, Illei GG, Hart TC (2006) Identification of parotid salivary biomarkers in Sjögren’s syndrome by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and two-dimensional difference gel electrophoresis. Rheumatology 45(9):1077–1086PubMedCrossRef Ryu OH, Arkinson JC, Hoehn GT, Illei GG, Hart TC (2006) Identification of parotid salivary biomarkers in Sjögren’s syndrome by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry and two-dimensional difference gel electrophoresis. Rheumatology 45(9):1077–1086PubMedCrossRef
20.
go back to reference Giusti L, Baldini C, Bazzichi L, Ciregia F, Tonazzini I, Mascia G, Giannaccini G, Bombardieri S, Lucacchini A (2007) Proteome analysis of whole saliva: a new tool for rheumatic diseases–the example of Sjögren’s syndrome. Proteomic 7(10):1634–1643CrossRef Giusti L, Baldini C, Bazzichi L, Ciregia F, Tonazzini I, Mascia G, Giannaccini G, Bombardieri S, Lucacchini A (2007) Proteome analysis of whole saliva: a new tool for rheumatic diseases–the example of Sjögren’s syndrome. Proteomic 7(10):1634–1643CrossRef
21.
go back to reference Srea EA, Routsias JG, Samiotaki M, Panayotou G, Papalambros E, Moutsopoulos HM, Tzioufas AG (2007) Analysis of parotid glands of primary Sjögren’s syndrome patients using proteomic technology reveals altered autoantigen compositon and novel antigenic targets. Clin Exp Immunol 147(1):81–89 Srea EA, Routsias JG, Samiotaki M, Panayotou G, Papalambros E, Moutsopoulos HM, Tzioufas AG (2007) Analysis of parotid glands of primary Sjögren’s syndrome patients using proteomic technology reveals altered autoantigen compositon and novel antigenic targets. Clin Exp Immunol 147(1):81–89
22.
go back to reference Peluso G, De Santis M, Inzitari C, Fanali C, Cabras T, Messana I, Castagnola M, Ferraccioli GF (2007) Proteomic study of salivary peptides and proteins in patients with Sjögren’s syndrome before and after pilocarpine treatment. Arthritis Rheum 56(7):2216–2222PubMedCrossRef Peluso G, De Santis M, Inzitari C, Fanali C, Cabras T, Messana I, Castagnola M, Ferraccioli GF (2007) Proteomic study of salivary peptides and proteins in patients with Sjögren’s syndrome before and after pilocarpine treatment. Arthritis Rheum 56(7):2216–2222PubMedCrossRef
23.
go back to reference Zoukhri D, Rawe I, Singh M, Brown A, Kublin CL, Dawson K, Haddon WF, White EL, Hanley KM, Tusé D, Malyj W, Papas A (2012) Discovery of putative salivary biomarkers for Sjögren’s syndrome using high resolution mass spectrometry and bioinformatics. J Oral Sci 54(1):61–70PubMedCrossRef Zoukhri D, Rawe I, Singh M, Brown A, Kublin CL, Dawson K, Haddon WF, White EL, Hanley KM, Tusé D, Malyj W, Papas A (2012) Discovery of putative salivary biomarkers for Sjögren’s syndrome using high resolution mass spectrometry and bioinformatics. J Oral Sci 54(1):61–70PubMedCrossRef
24.
go back to reference Wei P, Kuo WP, Chen F, Hua H (2013) Diagnostic model of saliva peptide finger print analysis of primary Sjögren’s syndrome patients by using weak cation exchange magnetic beads. Biosci Rep 16(4):e00051. doi:10.1042/BSR20130022 Wei P, Kuo WP, Chen F, Hua H (2013) Diagnostic model of saliva peptide finger print analysis of primary Sjögren’s syndrome patients by using weak cation exchange magnetic beads. Biosci Rep 16(4):e00051. doi:10.​1042/​BSR20130022
Metadata
Title
Establishment of a novel diagnostic model for Sjögren’s syndrome by proteomic fingerprinting
Authors
Yuhui Li
Xiaolin Sun
Xuewu Zhang
Yuqin Yang
Rulin Jia
Xu Liu
Ru Li
Yanying Liu
Zhanguo Li
Publication date
01-12-2014
Publisher
Springer London
Published in
Clinical Rheumatology / Issue 12/2014
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-014-2762-4

Other articles of this Issue 12/2014

Clinical Rheumatology 12/2014 Go to the issue