title: Inflammatory profile and response to anti-tumor necrosis factor therapy in patients with chronic pulmonary sarcoidosis.
abstract: Sarcoidosis is an inflammatory, granulomatous disease of unknown etiology that most commonly afflicts the lungs. Despite aggressive immunosuppressive therapies, many sarcoidosis patients still chronically present significant symptoms. Infliximab, a therapeutic tumor necrosis factor alpha (TNF-α) monoclonal antibody (MAb), produced a small but significant improvement in forced vital capacity (FVC) in sarcoidosis patients in a double-blind, placebo-controlled, phase II clinical trial. In the current study, serum samples from this clinical trial were assessed to evaluate the underlying hypothesis that treatment with infliximab would reduce systemic inflammation associated with sarcoidosis, correlating with the extent of clinical response. A 92-analyte multiplex panel was used to assess the expression of serum proteins in 134 sarcoidosis patients compared with sera from 50 healthy controls. A strong systemic inflammatory profile was associated with sarcoidosis, with 29 analytes significantly elevated in sarcoidosis (false-discovery rate, <0.05 and >50% higher than controls). The associated analytes included chemokines, neutrophil-associated proteins, acute-phase proteins, and metabolism-associated proteins. This profile was evident despite patients receiving corticosteroids and immunosuppressive therapies. Following infliximab treatment, sarcoidosis patients expressing the highest levels of TNF-α, who had more severe disease, had the greatest improvement in FVC and reduction in serum levels of the inflammatory proteins MIP-1β and TNF-RII. This study supports the need for further exploration of anti-TNF therapy for chronic sarcoidosis patients, particularly for those expressing the highest serum levels of TNF-α.
authors.affiliation: Department of Biomarkers, Centocor Research & Development, Inc., 145 King of Prussia Road, Radnor, PA 19087, USA. mloza@its.jnj.com
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Loza
authors.forename: Carrie
authors.initials: C
authors.lastname: Brodmerkel
authors.forename: Roland M
authors.initials: RM
authors.lastname: Du Bois
authors.forename: Marc A
authors.initials: MA
authors.lastname: Judson
authors.forename: Ulrich
authors.initials: U
authors.lastname: Costabel
authors.forename: Marjolein
authors.initials: M
authors.lastname: Drent
authors.forename: Mani
authors.initials: M
authors.lastname: Kavuru
authors.forename: Susan
authors.initials: S
authors.lastname: Flavin
authors.forename: Kim Hung
authors.initials: KH
authors.lastname: Lo
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Barnathan
authors.forename: Robert P
authors.initials: RP
authors.lastname: Baughman
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage*; D007249:Inflammation / Q000473:pathology*; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D017565:Sarcoidosis, Pulmonary / Q000188:drug therapy* / Q000473:pathology*; D044967:Serum / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D007155:Immunologic Factors; D010919:Placebos; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab