Attenuated Apoptosis of B Cell Activating Factor–Expressing Cells in Primary Sjögren's Syndrome

Szodoray, Péter; Jellestad, Stig; Teague, Maria Ohlsson; Jönsson, Roland

doi:10.1097/01.lab.0000059930.92336.e2

Cited by 66 publications

(51 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Transgenic mice overexpressing BAFF are shown to develop autoimmune disorders that are similar to SLE in humans [15,16]. Consistent with these observations, BAFF levels are higher in human autoimmune diseases, such as SLE, Sjogren syndrome, and rheumatoid arthritis [17][18][19][20]. In addition to autoimmune diseases, malignant B cells from non-Hodgkin's lymphoma and multiple myeloma patients also express abnormal levels of BAFF protein, which plays a role in survival of malignant cells [21,22].…”

Section: Introductionsupporting

confidence: 60%

Functional implication of BAFF synthesis and release in gangliosides-stimulated microglia

Kim

Park

Jou

et al. 2009

Journal of Leukocyte Biology

View full text Add to dashboard Cite

BAFF is a recently identified member of the TNF ligand superfamily that plays a critical role in B cell differentiation, survival, and regulation of Ig production. In the present study, we examined whether BAFF is expressed in microglia, and the expression and release of BAFF are regulated by gangliosides. The results showed that BAFF was expressed and released in rat primary microglia as well as in BV-2 cells. Furthermore, its expression and release were increased by gangliosides stimulation and regulated by JAK-STAT, especially the STAT1-and STAT3-dependent signaling pathways. It was of particular interest to observe that SP600125 and SB203580, specific inhibitors of JNK and p38, did not inhibit BAFF synthesis but inhibited the release of sBAFF in gangliosides-treated cells by regulating furin expression, suggesting that the JNK and p38 signaling pathways regulate the release but not the synthesis of BAFF. Moreover, BV-2 cells expressed BAFF-R on their cell surface, and rat primary microglia expressed BAFF-R and TACI on their cell surface. rBAFF increased the release of cytokines, especially IL-6, TNF-␣, and IL-10, in rat primary microglia as well as in BV-2 cells. These findings imply that BAFF secreted by microglia may play important roles in CNS inflammation by regulating microglia as well as infiltrated B cells.

show abstract

Section: Introductionsupporting

confidence: 60%

Functional implication of BAFF synthesis and release in gangliosides-stimulated microglia

Kim

Park

Jou

et al. 2009

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…In human Sjö gren's syndrome, immunohistochemical evidence for BLyS production in epithelial cells of salivary glands exists. 28,36 BLySpositive monocytes, 37 B, 38 and T 37 lymphocytes as well as BAFF-R-positive B lymphocytes 38 infiltrating salivary glands in Sjö gren's syndrome have been demonstrated, similar to the BLyS-/BAFF-R-positive interstitial cell infiltrate seen in lupus nephritis. In human rheumatoid arthritis, different cells seem to express the B-cell survival factors: one immunohistochemical study found APRIL in germinal center positive synovitis in CD83-positive dendritic cells, whereas BLyS was derived from CD68-positive monocytes/macrophages.…”

Section: Discussionmentioning

confidence: 72%

Intrarenal production of B-cell survival factors in human lupus nephritis

et al. 2011

View full text Add to dashboard Cite

The B-cell survival factors APRIL and BLyS are important for B-cell maturation and activation and contribute to human autoimmune diseases. Interference with B-cell function by targeting these molecules is currently being investigated in large clinical trials for systemic lupus erythematosus. The local expression patterns of APRIL and BLyS have not been investigated in detail in kidneys with lupus nephritis. We studied the mRNA expression of APRIL, BLyS, and the corresponding receptors BCMA, TACI, and BAFF-R in microdissected human biopsies with proliferative lupus nephritis (n ¼ 25) and compared it with pretransplant biopsies of living donors (n ¼ 9). APRIL and BLyS mRNA levels were significantly higher in glomeruli of patients with proliferative lupus nephritis (12-and 30-fold, respectively). Tubulointerstitial expression of APRIL, BLyS, BCMA, and TACI was also significantly elevated. To localize the respective proteins in the kidney, APRIL, BLyS, and BAFF-R were studied by immunohistochemistry in renal biopsies with proliferative (n ¼ 21) or membranous (n ¼ 8) lupus nephritis. APRIL was prominently expressed in glomeruli with proliferative, but not membranous, lupus nephritis. The staining pattern was consistent with mesangial cells. A prominent accumulation of CD68-positive cells was present in glomeruli in association with APRIL expression. APRIL, BLyS, and BAFF-R were also expressed in interstitial inflammatory cell accumulation. This is the first study, which details local expression of APRIL and BLyS in glomeruli and tubulointerstitium of human proliferative lupus nephritis. This information might help define intrarenal effects of APRIL and BLyS inhibition in human lupus nephritis.

show abstract

“…We acknowledge that up-regulated levels of BAFF have previously been reported in the salivary glands of patients with primary SS (6,8), but we believe that the present study is the first to quantify the levels of BAFF in their saliva. High salivary BAFF levels correlated with the probing pocket depth score and subsequent bone loss in patients with periodontal disease (both those with and those without autoimmune disorders).…”

Section: Results and Conclusionmentioning

confidence: 94%

“…B cells proliferate, produce autoantibodies, and favor the development of primary SS. Further support for the importance of BAFF is provided by the fact that patients with primary SS have increased serum levels of BAFF (6), associated with autoantibodies (7), and they have high concentrations of BAFF within their salivary glands (8). Accordingly, the purpose of the present study was to compare the periodontal status of patients with primary SS with that of subjects who have xerostomia but do not fulfill the criteria for the disease, to compare the levels of BAFF in paired samples of saliva and serum, and to correlate the levels of BAFF with the periodontal indices.…”

mentioning

confidence: 99%

Is periodontal disease mediated by salivary baff in sjögren's syndrome?

Pers

d’Arbonneau

Devauchelle‐Pensec

et al. 2005

Arthritis & Rheumatism

View full text Add to dashboard Cite

ObjectiveTo correlate the periodontal status of 15 patients with primary Sjögren's syndrome (SS) with their salivary levels of BAFF.MethodsThe periodontal status of 15 patients who fulfilled the criteria for primary SS was compared with that of 15 controls with xerostomia who did not fulfill the criteria for primary SS but had similar symptoms of dry mouth. The level of BAFF was measured in paired samples of saliva and serum using in‐house enzyme‐linked immunosorbent assays. Periodontitis was assessed by the plaque index, the modified gingival index, the papillary bleeding index, and the periodontal pocket depth.ResultsNotwithstanding the better oral hygiene practices of the patients with primary SS compared with those of the xerostomia controls and the subsequent reduction of their plaque index scores, complications of periodontitis, such as bleeding, gingival hypertrophy, and periodontal pockets, were not improved. This failure to ameliorate the complications of periodontitis in patients with primary SS was associated with high levels of BAFF in their saliva compared with the levels in xerostomia controls (7.4 ± 2.1 versus 1.0 ± 0.4 ng/ml [P < 0.002]). The levels of BAFF in saliva did not correlate with the levels in sera but did correlate with the periodontal pocket depth (P < 0.002).ConclusionThese findings are similar to the bone resorption observed in patients with rheumatoid arthritis. They suggest that the known effect of B cells in periodontitis would be partly mediated by salivary BAFF in patients with primary SS.

show abstract

Attenuated Apoptosis of B Cell Activating Factor–Expressing Cells in Primary Sjögren's Syndrome

Cited by 66 publications

References 26 publications

Functional implication of BAFF synthesis and release in gangliosides-stimulated microglia

Functional implication of BAFF synthesis and release in gangliosides-stimulated microglia

Intrarenal production of B-cell survival factors in human lupus nephritis

Is periodontal disease mediated by salivary baff in sjögren's syndrome?

Contact Info

Product

Resources

About