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Unsolved mystery of Fas: mononuclear cells may have trouble dying in patients with Sjögren's syndrome
I. Lindrova, M. Kolackova, T. Svadlakova, R. Vankova, M. Chmelarova, M. Rosecka, E. Jozifkova, M. Sembera, J. Krejsek, R. Slezak
Language English Country England, Great Britain
Document type Journal Article
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BioMedCentral
from 2000-12-01
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Free Medical Journals
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- MeSH
- Annexin A5 MeSH
- fas Receptor metabolism MeSH
- Apoptosis MeSH
- Autoimmune Diseases * MeSH
- Humans MeSH
- bcl-2-Associated X Protein metabolism MeSH
- Interleukin-2 Receptor alpha Subunit metabolism MeSH
- Sjogren's Syndrome * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
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.
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