Medizinische Universität Graz - Research portal
Selected Publication:
Pietsch, D.
Differences in JAK- STAT signaling in leukocytes of the peripheral blood in psoriatic arthritis
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2022. pp. 84
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- Authors Med Uni Graz:
- Advisor:
- Fessler Johannes
- Stradner Martin Helmut
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- Abstract:
- Background and purpose: The immunopathological processes in psoriatic arthritis (PsA) are orchestrated through cells of the innate and adaptive immune system and different cytokines. These cytokines, in large parts, use intracellular molecules that belong to the JAK/ STAT signaling pathway and that can alter gene expression in different cells. An important sign of activation in this pathway is the phosphorylation of STAT molecules. In this work, we investigate whether there are differences in phosphorylation levels between PsA patients with different disease activity and furthermore, if the patients can be divided into subgroups according to their STAT phosphorylation profile. Methods: Prospective cross-sectional study on 49 patients with PsA [median age 57 (50.0,62.0), 42,9% female, Disease Activity Index in Psoriatic Arthritis (DAPSA) 5.0 (1.0, 11.4), 18.4% Moderate / High disease activity (MoDA/ HDA), 81.6% Low disease activity / remission (LDA/ REM)]. Flow Cytometry was used to determine the phosphorylation levels of STAT molecules (pSTATs) in different immune cells of the peripheral blood. The geometric mean fluorescence intensity (gMFI) of the given STAT molecule in the immune cell was used to detect differences with several statistical tests & procedures. Results: We found statistically significant differences between the groups LDA/ REM and MoDA/ HDA in the levels of pSTAT3 in naïve / memory CD4+ and CD4- T cells as well as in pSTAT1 in Granulocytes & Monocytes. We further could divide the PsA patients into 4 clusters based on the STAT phosphorylation levels. These clusters differed significantly in DAPSA, CRP, CD19+ cell frequency, pSTAT3 levels in Monocytes, B cells, naïve & memory CD4+ and CD4- T cells, pSTAT5 in naïve & memory CD4+ T cells, pSTAT1 in T Cells and pSTAT4 in Granulocytes, Monocytes, B cells, and naïve CD4+ and CD4- T cells. Conclusion: This work shows that PsA patients with differences in disease activity also differed in the STAT phosphorylation levels of immune cells of the peripheral blood. Furthermore, the patients could be divided into subgroups based on the phosphorylation patterns and the clusters differed in clinical as well as biological parameters.