title: Serum macrophage inhibitory cytokine 1 in rheumatoid arthritis: a potential marker of erosive joint destruction.
abstract: OBJECTIVE
  The transforming growth factor beta superfamily member macrophage inhibitory cytokine 1 (MIC-1) is expressed upon macrophage activation, regulated by the p53 pathway, and linked to clinical events in atherosclerosis and cancer. Since rheumatoid arthritis (RA) shares similar etiopathologic mechanisms with the above diseases, we sought to determine the clinical utility of determining MIC-1 serum levels and MIC-1 genotype in the management of RA.
  
  
  METHODS
  Ninety-one RA patients were recruited. Serum was collected from 83 of these patients and synovial biopsy samples were collected from the remaining 8 patients. Of the 83 patients from whom serum was collected, 61 were treated on an outpatient basis (defined as having nonsevere disease), and 22 patients went on to undergo hemopoietic stem cell transplantation (HSCT) (defined as having severe disease).
  
  
  RESULTS
  Serum levels of MIC-1 were higher in RA patients and reflected disease severity independently of classic disease markers. MIC-1 was detected in rheumatoid synovial specimens, and allelic variation of MIC-1 was associated with earlier erosive disease and severe treatment-resistant chronic RA. Additionally, algorithms including serum and/or allelic variation in MIC-1 predicted response to HSCT, the presence of severe disease, and joint erosions.
  
  
  CONCLUSIONS
  Determination of serum levels of MIC-1 and MIC-1 genotype may be clinically useful in the management of RA as well as in selection of patients for HSCT, since they predict disease course and response to therapy. The data indicate a potential role for MIC-1 in RA pathogenesis. These results warrant larger prospective studies to fully delineate and confirm a role for MIC-1 genotyping and serum estimation in patient selection for HSCT and in the management of RA.
authors.affiliation: St. Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.forename: John
authors.initials: J
authors.lastname: Moore
authors.forename: Heiko
authors.initials: H
authors.lastname: Johnen
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Smeets
authors.forename: Asne R
authors.initials: AR
authors.lastname: Bauskin
authors.forename: Tamara
authors.initials: T
authors.lastname: Kuffner
authors.forename: Helen
authors.initials: H
authors.lastname: Weedon
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Milliken
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Smith
authors.forename: Samuel N
authors.initials: SN
authors.lastname: Breit
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D019485:Bone Morphogenetic Proteins / Q000097:blood* / Q000235:genetics; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D055436:Growth Differentiation Factor 15; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007596:Joints / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein