Increased serum concentrations of neutrophil-derived protein S100A12 in heterozygous carriers of MEFV mutations

Clin Exp Rheumatol. 2015 Nov-Dec;33(6 Suppl 94):S113-6. Epub 2015 Oct 19.

Abstract

Objectives: 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.

MeSH terms

  • Adult
  • Asymptomatic Diseases
  • Biomarkers / blood
  • Blood Sedimentation
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis
  • Exons
  • Familial Mediterranean Fever / blood*
  • Familial Mediterranean Fever / diagnosis
  • Familial Mediterranean Fever / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote*
  • Humans
  • Inflammation Mediators / blood*
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Pyrin
  • S100A12 Protein / blood*
  • Surveys and Questionnaires
  • Time Factors
  • Up-Regulation

Substances

  • Biomarkers
  • Cytoskeletal Proteins
  • Inflammation Mediators
  • MEFV protein, human
  • Pyrin
  • S100A12 Protein
  • S100A12 protein, human