Seroreactivity against glycolytic enzymes in inflammatory bowel disease.
BACKGROUND
Patients with inflammatory bowel disease (IBD) carry autoantibodies such as perinuclear antineutrophil cytoplasmic antibodies. The aim of the current study was to further characterize the immune reactivity in IBD.


METHODS
We used an immunoproteomic approach with extracts from granulocytes and serum from ulcerative colitis (UC) patients and controls to identify target antigens. By means of Western blot analysis, we screened 60 UC and 60 Crohn's disease (CD) patients, 60 diseased, and 60 healthy controls for the antibodies. We performed gene array experiments on RNA extracted from colonic mucosal biopsies from 42 IBD patients and six controls.


RESULTS
We identified aldolase A, phosphoglycerate mutase, alpha-enolase, triose-phosphate isomerase, and malate dehydrogenase as target antigens in IBD. Seroreactivity to at least one of these five antigens was detected in 53.3% of UC patients, 38.3% of CD patients, and 8.3% of controls. Seroreactivity to at least two antigens was detected in 16.7% of UC patients, 11.7% of CD patients, and none of the controls. Gene array experiments showed a significant upregulation of aldolase A, phosphoglycerate mutase, alpha-enolase, and pyruvate kinase mRNA in biopsies from IBD patients, but not controls. UC and CD patients also showed enhanced expression of hypoxia-inducible factor-1, a transcription factor that induces expression of glycolytic enzymes.


CONCLUSIONS
IBD patients show strong seroreactivity toward enzymes involved in the glycolysis. IBD patients also have increased colonic mRNA expression of glycolytic enzymes, which is triggered by hypoxia through the transcription factor HIF-1.
Vermeulen
Nathalie
N
Department of Internal Medicine, University Hospitals Leuven, Leuven, Belgium.
Vermeire
Severine
S
Arijs
Ingrid
I
Michiels
Georges
G
Ballet
Vera
V
Derua
Rita
R
Waelkens
Etienne
E
Van Lommel
Leentje
L
Schuit
Frans
F
Rutgeerts
Paul
P
Bossuyt
Xavier
X
D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000201:enzymology*; D003424:Crohn Disease / Q000201:enzymology*; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D006019:Glycolysis; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome / Q000032:analysis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers; D020543:Proteome; D012333:RNA, Messenger