Increased serum concentrations of neutrophil-derived protein S100A12 in heterozygous carriers of MEFV mutations.
OBJECTIVE
To assess subclinical inflammation in heterozygous carriers of Mediterranean fever (MEFV) gene mutations, analysis of classical inflammation markers and S100A12 was performed.


METHODS
Exons 2, 3, and 10 of the MEFV gene, C-reactive protein (CRP), serum amyloid A protein (SAA), procalcitonin (PCT), and S100A12 concentrations, erythrocyte sedimentation rate (ESR), and differential blood count were analysed in apparently healthy parents (n=26) of homozygous children with familial Mediterranean fever (FMF). Their general health condition was assessed by a standardised questionnaire. In order to collect data on the disease course, subjects were reevaluated after 5 years by means of telephone interview and/or questionnaire.


RESULTS
Twenty-two individuals with one typical mutation in the MEFV gene were included. Mean values (mean±SEM) of classical inflammation markers were within the normal range (ESR of 11.7±1.9 mm/h, SAA 4.7±0.4 mg/l, CRP 0.26±0.04 mg/dl), while PCT was non-detectable in all cases (<0.1 μg/l). Eleven subjects showed elevated S100A12 levels [>140 ng/ml] with a mean concentration of 205±43 ng/ml. Thus, the mean value of S100A12 was 1.5-fold higher than the regular cut-off.


CONCLUSIONS
50% of the heterozygous MEFV mutation carriers exhibited elevated S100A12 levels, supporting previous observations that S100 molecules are very sensitive biomarkers of subclinical inflammation. Possibly, S100A12 could be a prognostic biomarker to detect individuals at risk of FMF manifestation who might benefit from colchicine therapy.
Department of Paediatric Pneumology and Immunology, Charité University Hospital Berlin, Germany.
Mareike
M
Lieber
Department of Paediatric Pneumology and Immunology, Charité University Hospital Berlin, Germany. tilmann.kallinich@charite.de.
Tilmann
T
Kallinich
Department of Clinical Chemistry, Großhadern, University of Munich, Munich, Germany.
Peter
P
Lohse
German Rheumatism Research Centre Berlin, a Leibniz Institute, Berlin; and Institute for Social Medicine, Epidemiology and Health Economics, Charité Universitaetsmedizin, Berlin, Germany.
Jens
J
Klotsche
Department of Paediatric Rheumatology and Immunology, University Children's Hospital Münster, Germany.
Dirk
D
Holzinger
Department of Paediatric Rheumatology and Immunology, University Children's Hospital Münster, Germany.
Dirk
D
Foell
Department of Paediatric Rheumatology and Immunology, University Children's Hospital Münster, Germany.
Helmut
H
Wittkowski
D000328:Adult; D058070:Asymptomatic Diseases; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D010505:Familial Mediterranean Fever / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D000071198:Pyrin; D000067616:S100A12 Protein / Q000097:blood*; D011795:Surveys and Questionnaires; D013997:Time Factors; D015854:Up-Regulation
D015415:Biomarkers; D003598:Cytoskeletal Proteins; D018836:Inflammation Mediators; C000604192:MEFV protein, human; D000071198:Pyrin; D000067616:S100A12 Protein; C090441:S100A12 protein, human