salivary glands of primary sj？grens syndrome patients express factors vital for plasma cell survival唾液腺初级sj gren综合征患者表达因素对浆细胞的生存至关重要.pdfVIP

Szyszko et al. Arthritis Research Therapy 2011, 13:R2 /content/13/1/R2 RESEARCH ARTICLE Open Access Salivary glands of primary Sjögren’s syndrome patients express factors vital for plasma cell survival 1,2* 1 2 3 1,4 Ewa A Szyszko , Karl A Brokstad , Gunnvor Øijordsbakken , Malin V Jonsson , Roland Jonsson , Kathrine Skarstein2 Abstract Introduction: The presence of circulating Ro/SSA and La/SSB autoantibodies has become an important marker in the classification criteria for primary Sjögren’s syndrome (pSS). Plasma cells producing these autoantibodies are mainly high affinity plasma cells originating from germinal centre reactions. When exposed to the right microenvironment these autoimmune plasma cells become long-lived and resistant to immunosuppressive treatment. Since autoimmune plasma cells have been detected in the salivary glands of SS patients, we wanted to investigate if the glandular microenvironment is suitable for plasma cell survival and if glandular residing plasma cells are the long-lived plasma cell subset. Methods: Single, double and triple immunohistochemistry as well as immunofluorescence staining was performed on minor salivary gland tissue retrieved from pSS, chronically inflamed and normal subjects. Results: We detected significant numbers of CD138+, non-proliferating, Bcl-2 expressing plasma cells in the salivary glands of pSS patients with high focus score (FS). Furthermore, we demonstrated that CXCL12 and interleukin (IL)-6 survival factors were highly expressed in pSS salivary gland epithelium and by focal mononuclear infiltrating cells. Notably, adipocytes when present in the salivary gland tissue were an important source of CXCL12. We clearly d