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Signal transducers and activators of transcription (Stats) are essential for cytokine receptor signaling. Stat4 is found in lymphocytes and activated monocytes, where it is tyrosine-phosphorylated after IL-12 or (human) interferon-alpha bind their respective receptors. Stat4 plays a significant role in the development of Th1 cells: Stat4-/- mice lack such cells and are Th2-shifted. Moreover, Stat4 expression is known to be influenced by lymphocyte activation. We therefore investigated the expression of Stat4 in human SLE.
Peripheral venous blood was drawn from 9 patients fulfilling ACR criteria for SLE and 7 healthy controls. Protein lysates were prepared from highly enriched T cells and standardized for protein, electropheresed on polyacrylamide gels and electrotransferred. Stat4 was detected using polyclonal antibodies, peroxidase-conjugated secondary antibodies and chemoluminescence.
Stat4 protein was clearly detectable in 5 out of 7 healthy controls. In contrast, the T cells of only 1 of 9 SLE patients contained Stat4. This difference was statistically significant (P = 0.035 in Fisher's exact test). This result was independent of disease activity or therapy. Lysates from crude PBMC lysates gave similar results, which would be expected, given the normal cellular distribution of Stat4, but some SLE lysates contained additional bands of similar size.
The lack of Stat4 protein in SLE T lymphocytes may have immunological consequences by hampering Th1 answers. It is unclear at the moment whether the differences observed are due to constant immune stimulation.