Serum macrophage inhibitory cytokine 1 in rheumatoid arthritis: a potential marker of erosive joint destruction.
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.
Brown
David A
DA
St. Vincent's Hospital and University of New South Wales, Sydney, New South Wales, Australia.
Moore
John
J
Johnen
Heiko
H
Smeets
Tom J
TJ
Bauskin
Asne R
AR
Kuffner
Tamara
T
Weedon
Helen
H
Milliken
Samuel T
ST
Tak
Paul P
PP
Smith
Malcolm D
MD
Breit
Samuel N
SN
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
D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein