Circulating concentrations of follistatin-like 1 in healthy individuals and patients with acute coronary syndrome as assessed by an immunoluminometric sandwich assay.
BACKGROUND
Follistatin-like 1 (FSTL1) is a 308-amino acid secreted glycoprotein. Tissue levels of FSTL1 are induced in animal models and patients with chronic inflammatory and cardiovascular disease. We hypothesized that FSTL1 can be measured in the human circulation and used as a biomarker in acute coronary syndrome (ACS).


METHODS
We developed an immunoluminometric assay (ILMA), assessed the preanalytic characteristics of FSTL1, and determined circulating FSTL1 concentrations in 120 apparently healthy individuals and 216 patients with ACS.


RESULTS
The assay had a limit of detection of 0.17 microg/L, limit of quantification of 1.02 microg/L, intraassay imprecision of < or =12.7%, and interassay imprecision of < or =15.4%. Selectivity was demonstrated with size-exclusion chromatography and lack of cross-reactivity with related proteins. The assay was not appreciably influenced by unrelated biological substances. FSTL1 in serum or whole blood was stable at room temperature for 48 h and was resistant to 4 freeze-thaw cycles. Measured FSTL1 concentrations in citrated plasma and heparin-treated plasma were 18% and 17% lower, respectively, than concentrations measured in serum. Apparently healthy individuals presented with a median FSTL1 serum concentration of 7.18 (range 1.06-18.49) microg/L. Serum FSTL1 concentrations were increased in ACS and related to the risk of all-cause mortality during follow-up.


CONCLUSIONS
The ILMA permits detection of FSTL1 in human serum and plasma. We expect that the favorable preanalytic characteristics of FSTL1 and the reference limits defined here for apparently healthy individuals will facilitate future studies of FSTL1 as a biomarker in various disease settings, including ACS.
Widera
Christian
C
Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Horn-Wichmann
Rüdiger
R
Kempf
Tibor
T
Bethmann
Kerstin
K
Fiedler
Beate
B
Sharma
Sarita
S
Lichtinghagen
Ralf
R
Leitolf
Holger
H
Ivandic
Boris
B
Katus
Hugo A
HA
Giannitsis
Evangelos
E
Wollert
Kai C
KC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood* / Q000401:mortality; D005260:Female; D038702:Follistatin-Related Proteins / Q000097:blood*; D006801:Humans; D007118:Immunoassay; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D055815:Young Adult
D015415:Biomarkers; D038702:Follistatin-Related Proteins; C448799:FSTL1 protein, human