T cell receptor Zeta chain (TCRζ) expression in patients with idiopathic thrombocytopenic purpura

Background: T cell receptor zeta chain (TCRζ) plays a critical role in signal
transduction via TCR. Defective signaling through TCRζ-CD3 components may
disrupt peripheral T cell tolerance to autoantigen, giving rise to a variety of
autoimmune diseases. The aim of this work was to evaluate TCRζ chain gene
expression in patients with ITP, thereby to understand the functioning status of T cells
and its possible contribution to disease outcome. Methods: SYBR Green based Realtime
relative quantitative PCR (qRT-PCR) was used to evaluate TCRζ gene
expression in 49 ITP patients and 35 age- and sex-matched control subjects. Results:
Patients in acute phase of ITP had a significantly lower TCRζ gene expression
compared to those in chronic phase and those of the control group; on the other hand
TCRζ gene expression was significantly lower in chronic ITP patients than in
controls. Patients with active ITP had a significantly lower TCRζ gene expression
compared to those in remission and those of control group (P < 0.001). TCRζ gene
expression was significantly lower in ITP patients in remission state in comparison to
the control group. Treated ITP patients had a significantly higher TCRζ gene
expression compared to untreated patients, however TCRζ gene expression in the
treated group was still significantly lower compared to controls (P<0.001). Complete
responders had a significantly higher TCRζ gene expression compared to non
responders (P<0.001), while no significant difference was found between nonresponders
and partial responders as regards TCRζ gene expression (P>0.05). The
level of TCRζ gene expression in complete responders was still significantly lower
compared to controls (P<0.001). Sequential analyses for TCRζ gene expression in 6
patients with stable disease revealed no significant difference in median TCRζ gene
expression values in the 3 consequents analyses (P>0.05). TCRζ gene expression
showed no significant correlation with any of the clinical or hematological data.
Conclusion: From these data, it could be suggested that downregulation of TCRζ
may represent intrinsic defects of potential pathogenetic significance for ITP.
Therapy targeted to normalization of TCRζ expression may represent a new strategy
for treatment of ITP patients after being validated in clinical trials.