title: Serum protein profile of Crohn's disease treated with infliximab.
abstract: The infliximab (IFX) has dramatically improved the treatment of Crohn's disease (CD). However, the need for predictive factors, indicative of patients' response to IFX, has yet to be met. In the current study, proteomics technologies were employed in order to monitor for differences in protein expression in a cohort of patients following IFX administration, aiming at identifying a panel of candidate protein biomarkers of CD, symptomatic of response to treatment. We enrolled 18 patients, who either had achieved clinical and serological remission (Rm, n=6), or response (Rs, n=6) and/or were PNRs (n=6), to IFX. Serum samples were subjected to two-dimensional Gel Electrophoresis. Following evaluation of densitometrical data, protein spots exhibiting differential expression among the groups, were further characterized by MALDI-TOF-MS. Identified proteins where evaluated by immunoblot analysis while functional network association was carried out to asses significance. Proteins apolipoprotein A-I (APOA1), apolipoprotein E (APOE), complement C4-B (CO4B), plasminogen (PLMN), serotransferrin (TRFE), beta-2-glycoprotein 1 (APOH), and clusterin (CLUS) were found to be up-regulated in the PNR and Rs groups whereas their levels displayed no changes in the Rm group when compared to baseline samples. Additionally, leucine-rich alpha-2-glycoprotein (A2GL), vitamin D-binding protein (VTDB), alpha-1B-glycoprotein (A1BG) and complement C1r subcomponent (C1R) were significantly increased in the serum of the Rm group. Through the incorporation of proteomics technologies, novel serum marker-molecules demonstrating high sensitivity and specificity are introduced, hence offering an innovative approach regarding the evaluation of CD patients' response to IFX therapy.
authors.affiliation: Department of Basic Medical Sciences, Laboratory of Biology, School of Medicine, University of Athens, Greece; Laboratory of Cell and Gene Therapy Foundation for Biomedical Research of the Academy of Athens (IIBEAA), Greece. Electronic address: mgazouli@med.uoa.gr.
authors.forename: Maria
authors.initials: M
authors.lastname: Gazouli
authors.forename: Athanasios K
authors.initials: AK
authors.lastname: Anagnostopoulos
authors.forename: Aggeliki
authors.initials: A
authors.lastname: Papadopoulou
authors.forename: Anna
authors.initials: A
authors.lastname: Vaiopoulou
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Papamichael
authors.forename: Gerassimos
authors.initials: G
authors.lastname: Mantzaris
authors.forename: George E
authors.initials: GE
authors.lastname: Theodoropoulos
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Anagnou
authors.forename: George Th
authors.initials: GT
authors.lastname: Tsangaris
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000097:blood; D001057:Apolipoproteins E / Q000097:blood; D015415:Biomarkers / Q000097:blood; D051152:Clusterin / Q000097:blood; D015923:Complement C1r / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D010958:Plasminogen / Q000378:metabolism; D040901:Proteomics; D012074:Remission Induction; D014168:Transferrin / Q000378:metabolism; D015854:Up-Regulation; D014809:Vitamin D-Binding Protein / Q000097:blood; D055815:Young Adult; D053482:beta 2-Glycoprotein I / Q000097:blood
chemical_list: C048566:A1BG protein, human; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000911:Antibodies, Monoclonal; D016632:Apolipoprotein A-I; D001057:Apolipoproteins E; D015415:Biomarkers; D051152:Clusterin; D006023:Glycoproteins; D007136:Immunoglobulins; C015246:LRG1 protein, human; D014168:Transferrin; D014809:Vitamin D-Binding Protein; D053482:beta 2-Glycoprotein I; D015935:Complement C4b; D010958:Plasminogen; D000069285:Infliximab; D015923:Complement C1r
keywords: Crohn's disease; Inflammatory bowel disease; Infliximab; Proteomics