Background The Mammalian Target of Rapamycin (mTOR), a multiprotein complex, controls cell growth, proliferation, survival and plays an important role in immunity and inflammation. Transforming Growth Factor-β1 (TGF- β1) leads to an increase in mTOR levels by protein kinase B (PKB or Akt) pathway. Phosphatase and tensin homolog (PTEN) affects mTOR pathway by inhibiting Akt. Recently, increased activities of TGF-β1 and mTOR were established in a mouse model of SSc. However the role of mTOR pathway, which might be a potential treatment target, in the human salivary gland inflammation is not evaluated systematically before.
Objectives Therefore, we aimed to examine the activity of mTOR pathway and TGF-β1 in human minor salivary gland biopsies of Sjogren's Syndrome (SjS) and systemic sclerosis (SSc) patients.
Methods Immunohistochemical technique was used to analyze the expression of mTOR, PTEN and TGF-β1 in human minor salivary gland biopsies of SjS, SSc and SjS-SSc overlap patients. Immunohistochemical staining was evaluated by light microscopy and staining intensity was scored semi-quantitatively (Figure 1). The biopsy specimens were also examined for the degree of fibrosis.
Results Formalin fixed sections of minor salivary gland biopsies of 58 SjS (57 female [98.3%]), 14 SSc (13 female [92.8%]) and 23 SjS-SSc overlap patients (all female) were included in the study. All biopsy specimens of SjS and overlap patients had a focus score of ≥1. There is no significant difference regarding mTOR expression between groups (P=0.622). mTOR expression was found in 94.4% in SjS group, 100% in overlap and 90% in SSc patients. PTEN protein was expressed in 87.2% of patients with SjS, 57.9% of overlap and 100% of SSC patients and the difference was statistically different (P=0.023). Although ductal epithelial TGF-β1 expression was similar between groups (P=0.345), acinar cell expression is more frequent in SSc (72.7%) and overlap patients (85.7%) in comparison with SjS (58.2% and P=0.004). Additionally, most of the acinar TGF-β1 staining was strong positive in SSC patients (45.5% vs 19.0% and 3.6%).
Conclusions The results of our study showed that mTOR may be one of the common pathways for the pathology/inflammation observed in both SjS and SSc. Thus, there may be a room for mTOR inhibitors for the treatment of both diseases. Additionally PTEN and TGF-β1 expression, in particular acinar TGF-β1 might be a distinctive feature of SSc.
Disclosure of Interest None declared