title: Immune response to extracellular matrix collagen in chronic hepatitis C-induced liver fibrosis.
abstract: Hepatitis C virus (HCV) infection and its recurrence after orthotopic liver transplantation (OLT) are associated with the remodeling of extracellular matrix (ECM) components [particularly collagen (Col)], which leads to fibrosis. Our aim was to determine whether the development of antibodies (Abs) to self-antigen Col in HCV-infected patients correlates with the fibrosis stage and the peripheral cytokine response. Patients with chronic HCV infection, patients with HCV recurrence after OLT who had undergone a biopsy procedure, and healthy control subjects were enrolled. The HCV subjects (n = 70) were stratified as follows: (1) a non-OLT group without fibrosis (Scheuer stages 0-2), (2) a non-OLT group with fibrosis (Scheuer stages 3-4), (3) a post-OLT group without fibrosis (Scheuer stages 0-2), and (4) a post-OLT group with fibrosis (Scheuer stages 3-4). Serum samples were analyzed for Abs against Col1, Col2, Col4, Col5, and vimentin with enzyme-linked immunosorbent assays. Serum levels of cytokines were measured with multiplex bead immunoassays. The levels of Abs to Col1 were higher in the fibrosis groups versus the no-fibrosis groups and the controls for both non-OLT patients (P < 0.001) and post-OLT patients (P = 0.01). There were increased levels of Abs to Col2, Col4, Col5, and vimentin in the non-OLT fibrosis group (Col2, P = 0.0001; Col4, P = 0.122; Col5, P < 0.0001; vimentin, P = 0.36) and in the post-OLT fibrosis group (Col2, P = 0.006; Col4, P = 0.19; Col5, P < 0.0001; vimentin, P = 0.24) in comparison with the no-fibrosis groups. The non-OLT and post-OLT fibrosis groups demonstrated significantly higher T helper 2 (T(h) 2) and T helper 17 (T(h) 17) cytokine levels and lower T helper 1 cytokine levels in comparison with the no-fibrosis groups. Our results demonstrate that in HCV-infected patients, the levels of Abs to ECM Col1, Col2, and Col5 positively correlate with liver fibrosis, which is associated with a predominantly T(h) 2 and T(h) 17 cytokine profile.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Brian B
authors.initials: BB
authors.lastname: Borg
authors.forename: Anil
authors.initials: A
authors.lastname: Seetharam
authors.forename: Vijay
authors.initials: V
authors.lastname: Subramanian
authors.forename: Haseeb Ilias
authors.initials: HI
authors.lastname: Basha
authors.forename: Mauricio
authors.initials: M
authors.lastname: Lisker-Melman
authors.forename: Kevin
authors.initials: K
authors.lastname: Korenblat
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Anderson
authors.forename: Surendra
authors.initials: S
authors.lastname: Shenoy
authors.forename: William C
authors.initials: WC
authors.lastname: Chapman
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Crippin
authors.forename: Thalachallour
authors.initials: T
authors.lastname: Mohanakumar
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D015331:Cohort Studies; D003094:Collagen / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006526:Hepatitis C / Q000150:complications / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007107:Immune System; D008103:Liver Cirrhosis / Q000150:complications* / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000378:metabolism
chemical_list: D016207:Cytokines; D012367:RNA, Viral; D003094:Collagen