Document Detail


Inflammatory profile and response to anti-tumor necrosis factor therapy in patients with chronic pulmonary sarcoidosis.
MedLine Citation:
PMID:  21508170     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Matthew J Loza; Carrie Brodmerkel; Roland M Du Bois; Marc A Judson; Ulrich Costabel; Marjolein Drent; Mani Kavuru; Susan Flavin; Kim Hung Lo; Elliot S Barnathan; Robert P Baughman
Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2011-04-20
Journal Detail:
Title:  Clinical and vaccine immunology : CVI     Volume:  18     ISSN:  1556-679X     ISO Abbreviation:  Clin. Vaccine Immunol.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-02     Completed Date:  2011-09-13     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  101252125     Medline TA:  Clin Vaccine Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  931-9     Citation Subset:  IM    
Affiliation:
Department of Biomarkers, Centocor Research & Development, Inc., 145 King of Prussia Road, Radnor, PA 19087, USA. mloza@its.jnj.com
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MeSH Terms
Descriptor/Qualifier:
Adult
Antibodies, Monoclonal / administration & dosage*
Biological Markers / blood
Chronic Disease
Female
Humans
Immunologic Factors / administration & dosage*
Inflammation / pathology*
Male
Middle Aged
Placebos / administration & dosage
Sarcoidosis, Pulmonary / drug therapy*,  pathology*
Serum / chemistry
Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Biological Markers; 0/Immunologic Factors; 0/Placebos; 0/TNF protein, human; 0/Tumor Necrosis Factor-alpha; 0/infliximab
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