Unsolved mystery of Fas: mononuclear cells may have trouble dying in patients with Sjögren's syndrome.

BACKGROUND: Patients with Sjögren's syndrome, like other patients with autoimmune disorders, display dysregulation in the function of their immune system. Fas and Fas Ligand (FasL) are among the dysregulated proteins. METHODS: We studied Fas and FasL on IL-2Rα+ cells and in serum of patients with Sjögren's syndrome (n = 16) and healthy individuals (n = 16); both from same ethnic and geographical background. We used flow cytometry and enzyme-linked immunosorbent for this purpose. We also measured the expression of Bcl-2 and Bax by reverse transcription quantitative real-time PCR (RT-qPCR) and percentage of apoptotic and dead cells using Annexin V and 7-AAD staining in lymphocytes. RESULTS: FasL was increased in patients' T and B cells while Fas was increased in patients' monocytes, T and B cells. No signs of increased apoptosis were found. sFas and sFasL in patients' serum were increased, although the increase in sFasL was not significant. We suspect an effect of non-steroidal anti-inflammatory therapy on B cells, explaining the decrease of the percentage Fas+ B cells found within our samples. In healthy individuals, there was a noticeable pattern in the expression of FasL which mutually correlated to populations of mononuclear cells; this correlation was absent in the patients with Sjögren's syndrome. CONCLUSIONS: Mononuclear cells expressing IL-2Rα+ had upregulated Fas in Sjögren's syndrome. However, the rate of apoptosis based on Annexin V staining and the Bcl-2/Bax expression was not observed in mononuclear cells. We suspect a functional role of abnormal levels of Fas and FasL which has not been cleared yet.

Increase of Intracellular BAFF in B Cells of Sjögren's Patients Is Not Affected by Decrease of BAFFR.

The presence of a broad spectrum of autoantibodies in Sjögren's syndrome (SjS) patients is the result of abnormal B-cell regulation that can be at least partially explained by abnormal BAFF/BAFFR regulation. The objective of this study was to determine both membrane and intracellular expression of BAFF/BAFFR in monocytes and B-cells in peripheral blood of 19 primary Sjögren's syndrome patients and 20 healthy controls using flow cytometry. We also measured sBAFF in serum. Compared to healthy controls, both surface and intracellular expression of BAFF was significantly increased in monocytes and B-cells of SjS patients. Also serum sBAFF level was elevated. Expression of BAFFR on B-cells of SjS patients was surprisingly decreased, but there was no clear increase or decrease within monocytes. Our results indicate that activated monocytes communicate with B-cells via BAFF and BAFFR, so that B-cells are stimulated, but BAFF is also produced to stimulate cells in autocrine way. The decrease of BAFFR expression in SjS patients suggests that there is the mechanism that attempts to take over in order to balance the high level of BAFF.