Research data from University of Helsinki update understanding of Sjogren syndrome
2007 NOV 22 -- "Sjogren's syndrome (SS), an autoimmune disease of exocrine glands, typically starts at the time of adrenopause. We undertook this study to test the hypothesis that SS is characterized by an insufficient androgen effect at the target tissue levelWe searched for androgen response elements (AREs) in the cysteine-rich secretory protein 3 (crisp-3) gene," scientists in Helsinki, Finland report. "Dehydroepiandrosterone (DHEA) responsiveness was experimentally studied using quantitative reverse transcriptase-polymerase chain reaction and immunofluorescence staining of human submandibular gland-derived acinar cells and labial salivary gland explants with or without DHEA. Finally, glandular and salivary CRISP-3 in healthy controls and SS patients was analyzed using immunohistochemistry, in situ hybridization, and enzyme-linked immunosorbent assay. Serum DHEA sulfate (DHEAS) and salivary DHEA levels were measured using a radioimmunometric methodLiterature analysis and a search for AREs in gene banks suggested androgen dependency of human CRISP-3, and this was verified by studies of human submandibular gland acinar cells cultured with or without DHEA, in which DHEA increased CRISP-3 messenger RNA (mRNA) levels (P = 0.018). This finding was confirmed by the results of DHEA stimulation of labial salivary gland explants. Glandular CRISP-3 mRNA and protein labeling was weak and diffuse, coupled with low secretion in saliva (mean +/- SEM 21.1 +/- 2.7 mu g CRISP-3/15 minutes in SS patients versus 97.6 +/- 12.0 mu g CRISP-3/15 minutes in healthy controls; P< 0.0001). Compared with healthy controls, SS patients had low serum levels of DHEAS (P = 0.008) and also low salivary levels of DHEA (mean +/- SEM 224 33 pmoles versus 419 98 pmoles; P = 0.005)CRISP-3 pathology was seen in acini remote from lymphocyte foci and is apparently not secondary to local inflammation, but may represent some systemic effect in SS. Indeed, androgen deprivation in the salivary glands of SS patients is evidenced both by low salivary levels of DHEA and by low levels of DHEA-regulated CRISP-3," wrote M. Laine and colleagues, University of Helsinki. The researchers concluded: "This may explain some of the characteristic features of SS." Laine and colleagues published their study in Arthritis and Rheumatism (Low salivary dehydroepiandrosterone and androgen-regulated cysteine-rich secretory protein 3 levels in Sjogren's syndrome. Arthritis and Rheumatism, 2007;56(8):2575-2584). For additional information, contact Y.T. Konttinen, University of Helsinki, Cent. Hospital, Dept. of Med Biomedical, PO Box 700, FIN-00029 Helsinki, Finland. The publisher's contact information for the journal Arthritis and Rheumatism is: Wiley-Liss, Division John Wiley & Sons Inc., 111 River St., Hoboken, NJ 07030, USA. Keywords: Finland, Helsinki, Sjogren Syndrome, University of Helsinki. This article was prepared by Hospital Law Week editors from staff and other reports. Copyright 2007, Hospital Law Week via NewsRx.com.
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