Neutrophil-derived S100A12 as novel biomarker of inflammation in familial Mediterranean fever.
OBJECTIVE
Familial Mediterranean fever (FMF) is characterised by recurrent periodic febrile attacks and persistent subclinical inflammation. The damage-associated molecular pattern (DAMP) protein S100A12 has proven to be a sensitive marker for disease activity and inflammation in numerous inflammatory disorders. The aim of this study was to analyse the role of S100A12 in the detection of inflammation in patients with FMF.


METHODS
52 children and adolescents with a clinical and/or genetic diagnosis of FMF were prospectively followed-up over 18 months (in total 196 visits). During clinical visits, erythrocyte sedimentation rate, C reactive protein, serum amyloid A and S100A12 serum concentrations were determined. Patients were categorised into four groups according to the clinical activity of FMF.


RESULTS
Serum concentrations of S100A12 were excessively increased in patients with a mean increase of about 290-fold in active FMF above normal controls. S100A12 decreased significantly after introduction of colchicine therapy. Serum concentrations of S100A12 were significantly higher in patients treated with colchicine with persistent symptoms (mean+/-SEM, 6260+/-2120 ng/ml) than in those with clinically controlled disease (440+/-80 ng/ml, p<0.001). In contrast to classical markers of inflammation, S100A12 was significantly elevated in clinically unaffected homozygous MEFV gene mutation carriers, indicating subclinical inflammation.


CONCLUSIONS
S100A12 is a valuable biomarker for monitoring disease activity, inflammation and response to colchicine treatment in patients with FMF. It might even be more sensitive in detecting subclinical inflammation than other available indicators.
Kallinich
Tilmann
T
Department of Pediatric Pneumology and Immunology, Charité-Universitaetsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany. tilmann.kallinich@charite.de
Wittkowski
Helmut
H
Keitzer
Rolf
R
Roth
Johannes
J
Foell
Dirk
D
D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003078:Colchicine / Q000627:therapeutic use; D003598:Cytoskeletal Proteins / Q000235:genetics; D010505:Familial Mediterranean Fever / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D009154:Mutation; D011446:Prospective Studies; D000071198:Pyrin; D009418:S100 Proteins / Q000097:blood*; D000067616:S100A12 Protein; D000685:Serum Amyloid A Protein / Q000032:analysis; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein; D003078:Colchicine