New Statistical Algorithms for the Analysis of Mass - FU Berlin, FB MI ...

4.5. IDENTIFICATION OF PROTEOMIC FINGERPRINTS IN BLOOD SERUM BY HIGH-SENSITIVE B
gestation becoming undetectable in the third trimester (Smyth et al., 2005).
(Radetti et al., 2006) showed that in children, the presence of goiter and
elevated TgAb at presentation, together with progressive increase in both
TPOab and TSH, may be predictive factors for the future development of
hypothyroidism.
So far several studies using proteomic techniques have been performed in
the area of thyroid diseases, mainly focusing on thyroid malignancies (Villanueva,
Martorella, Lawlor, Philip, Fleisher, Robbins and Tempst, 2006;
Brown et al., 2006; Suriano et al., 2006) and thyroid tissue pathology (Krause
et al., 2006; Torres-Cabala et al., 2006). However, the proteomic implications
of thyroid autoantibodies in the general population still remain unclear.
Due to the high clinical impact of thyroid autoantibodies even in a nonsymptomatic
population, this study investigates serum proteome profiles in an
apparently healthy population of blood donors to detect specific discriminating
proteome patterns which could very early point to the underlying autoimmune
processes in subjects with high thyroid autoantibody titers.
Study Participants
We included a sub-group of 870 healthy blood donors from one study center
(experienced and first time donors, which met the general principles of
donor selection and guidelines for deferral according to the German Guidelines
(Bundesgesundheitsblatt-Gesundheitsforschung-Gesundheitsschutz, 2000)) without
a personal history of a thyroid disease.
All donors filled out a questionnaire requesting information concerning a
family history of thyroid diseases, anthropometric data, smoking habits, and
medications. A total of 445 male and 425 female donors (age range, 18-68
years) were randomly included.
Thyroid ultrasonography was performed with an EUB-405 (Hitachi) with
a 7.5 MHz transducer. The thyroid volume was calculated as length · width
· depth · 0.479 for each lobe (J et al., 1981). Goiter was defined as a thyroid
volume exceeding 18 mL in women and 25 mL in men (Gutekunst et al., 1988).
Solid nodules were identified as differing from the healthy thyroid tissue in
pattern and ultrasonic echo intensity. The nodules were classified as isoechoic
if their texture closely resembled that of healthy thyroid tissue, hyperechoic if
more echogenic, and hypoechoic if less echogenic.
Venous blood was collected before the blood donation procedure started
using Sarstedt blood collection systems (Sarstedt, Nümbrecht, Germany). After
blood was centrifuged at 3000g for 15 min, the serum was aliquoted and
stored frozen at -80� until analysis.
All blood donors gave written consent for the participation in this study
and the study was also approved by the local ethics committee.
Study Description
Serum concentrations of TSH, FT4, FT3, T4, and T3 were measured by assays
on the ELECSYS system (Roche Diagnostics). The immunoreactivity of serum
TPO antibodies and Tg antibodies was measured on the same platform.
After thawing on ice peptide and protein purification and fractionation was
performed using a magnetic bead-based separation technique (ClinProtTM,