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

96 CHAPTER 4. (BIO-)MEDICAL APPLICATIONS
4.5 Identification of Proteomic Fingerprints in Blood
Serum by High-sensitive Bioinformatic Analysis
of MALDI-TOF MS Data for Detection of
Thyroid Diseases
This study was performed in close collaboration with Dr. Alexander Leichtle
from the Institute of Laboratory Medicine, Clinical Chemistry and Molecular
Diagnostics at University Leipzig.
Today, thyroid diseases are very common in the general population. For
example, up to one third of the adult German population suffers from nodular
thyroid disease (Hampel et al., 1995; Kratzsch et al., 2005). Studies have
shown that even failure of thyroid function shows a prevalence of up to 10%,
whereas the presence of positive anti-TPO antibodies (TPOAb) and of positive
anti-thyroglobulin antibodies (TgAb) is slightly higher in a US population
(13% and 11.5%) and more pronounced in white population, females and the
elderly ((Hollowell et al., 2002)). (Zphel et al., 2003) showed that TPOAb are
detectable in nearly all euthyroid individuals and TPOAb values in the low
measurable range are normally distributed.
Applying the National Academy of Clinical Biochemistry (NACB) decision
limits applied to older men or women, there is a markedly increased number
with “elevated” autoantibody levels compared to sex- and age-specific reference
intervals (O’Leary et al., 2006). TgAb and TPOAb are of immunoglobulin
G (IgG) class and have high affinities for their respective autoantigens.
(McLachlan and Rapoport, 2004) have shown that both autoantibodies are
markers of thyroid autoimmunity. While TgAb alone in the absence of TPOAb
is not significantly associated with thyroid disease, TPOAb and the combination
of both, TgAb and TPOAb, however, show strong association with clinical
hypo- and hyperthyroidism (Hollowell et al., 2002).
The familial aggregation of thyroid autoantibodies seems to be mainly
genetically determined (Brix et al., 2004): An exon 1 CTLA-4 gene polymorphism
G allele influences higher TPOAb and TgAb production, whereas the
C allele affects specifically TPOAb production in patients with Hashimoto’s
thyroiditis (Zaletel et al., 2006) suggesting CTLA-4 as a major thyroid autoantibody
susceptibility gene.
High TPOAb titre correlates with increased frequencies of T cells producing
Th/Tc1 cytokines, probably responsible for thyroid cell damage and/or
death in Hashimoto’s thyroiditis (Karanikas et al., 2005). TPOAb and TgAb
are both correlated with thyroid enlargement (Carl et al., 2006). The histological
diagnosis of Hashimoto’s thyroiditis can most precisely be predicted by
TgAb measurement (Kasagi et al., 1996).
(Engum et al., 2005) have found no associations between antithyroid antibodies
and depression or anxiety in a population-based study. However,
fibromyalgia patients had thyroid autoimmunity higher than control subjects
(Pamuk and Cakir, 2007). There is also a strong relation between thyroid
autoimmunity and breast cancer (Giustarini et al., 2006), but a direct relationship
between thyroid autoimmunity and breast cancer seems to be unlikely
(Kuijpens et al., 2005).
Pregnant women seem to have a lower positive rate of TPOAb than nonpregnant
women (3.3% vs 9.4%, p ¡ 0.01) (xia Guan et al., 2006) and the prevalence
of both, TPO and Tg antibodies shows a progressive decline throughout