Gene expression in endoprosthesis loosening: chitinase activity for early diagnosis?
The aim of the study was to identify markers for the early diagnosis of endoprosthesis loosening, for the differentiation between wear particle-induced and septic loosening and to gather new insights into the pathogenesis of endoprosthesis loosening. Gene expression profiles were generated from five periprosthetic membranes of wear particle-induced and five of infectious (septic) type using Affymetrix HG U133A oligonucleotide microarrays. The results of selected differentially expressed genes were validated by RT-PCR (n = 30). The enzyme activity and the genotype of chitinase-1 were assessed in serum samples from 313 consecutive patients hospitalized for endoprosthesis loosening (n = 54) or for other reasons, serving as control subjects (n = 259). Eight hundred twenty-four genes were differentially expressed with a fold change greater than 2 (data sets on http://www.ncbi.nlm.nih.gov/geo/ GSE 7103). Among these were chitinase 1, CD52, calpain 3, apolipoprotein, CD18, lysyl oxidase, cathepsin D, E-cadherin, VE-cadherin, nidogen, angiopoietin 1, and thrombospondin 2. Their differential expression levels were validated by RT-PCR. The chitinase activity was significantly higher in the blood from patients with wear particle-induced prosthesis loosening (p = 0.001). However, chitinase activity as a marker for early diagnosis has a specificity of 83% and a sensitivity of 52%, due to a high variability both in the disease and in the control group.
Morawietz
L
L
Institute for Pathology, Charité-University Medicine Berlin, Germany. lars.morawietz@charite.de
Weimann
A
A
Schroeder
J H
JH
Kuban
R J
RJ
Ungethuem
U
U
Kaps
C
C
Slevogt
H
H
Gehrke
T
T
Krukemeyer
M G
MG
Krenn
V
V
D000368:Aged; D000369:Aged, 80 and over; D001424:Bacterial Infections / Q000503:physiopathology; D002688:Chitinases / Q000097:blood* / Q000235:genetics; D042241:Early Diagnosis; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005838:Genotype; D006801:Humans; D008297:Male; D008566:Membranes / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010940:Plant Proteins; D011475:Prosthesis Failure; D016459:Prosthesis-Related Infections / Q000503:physiopathology; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity
D010940:Plant Proteins; D002688:Chitinases; C119825:chitinase C