BAFF and BAFF-R of peripheral blood and spleen mononuclear cells in idiopathic thrombocytopenic purpura

Abstract

BAFF (B-cell activating factor belonging to the TNF family) is an essential component of B-cell homeostasis, and is required for the normal survival and development of B cells. To further explore the role of this cytokine in the pathogenesis of idiopathic thrombocytopenic purpura (ITP), BAFF/BAFF-R (one of receptors of BAFF) expression levels were determined and the correlation between the clinical parameters and the BAFF expression levels was analyzed. A total of 57 patients with ITP were enrolled and 25 age and sex-matched healthy volunteers served as controls. Serum was obtained from 41 patients with ITP and 22 healthy volunteers and was analyzed with a commercial human soluble BAFF (sBAFF) ELISA kit. BAFF and BAFF-R mRNA expression of peripheral blood (PB) (n = 42) and splenocytes (SP) (n = 8) mononuclear cells (MNC) were determined by real-time quantitative PCR. The SPMNC of normal controls came from three hereditary spherocytosis patients who underwent splenectomy. The untreated patients with ITP had higher serum BAFF levels (Median 1430 pg/ml, Range: 534-5787 pg/ml) than those of normal controls (Median 1120 pg/ml, Range: 640-2376 pg/ml, p = 0.006) and treated ITP group (Median 662 pg/ml, Range 267-1265 pg/ml, p = 0.000). On the other hand, serum BAFF levels of treated patients with ITP were lower than those of normal controls (p = 0.001). There was a weak correlation (the Pearson correlation coefficient is - 0.242) between platelet count and BAFF (p = 0.064). However, BAFF levels did not correlate with platelet associated immunoglobulin or immunoglobulin levels. Moreover, the serum BAFF levels were not statistically different between acute and chronic ITP (p = 0.841). PBMNC of ITP had higher BAFF but not BAFF-R mRNA expression than that of normal controls. BAFF mRNA expression of SPMNC had a positive correlation with BAFF-R in ITP patients but not in PBMNC of normal controls and untreated ITP patients. The BAFF-R mRNA expression of SPMNC was shown to be 15.29 times higher than that of PBMNC in ITP. BAFF might contribute to autoimmunity and disease development in ITP. However, BAFF serum level must be carefully considered as a surrogate marker of disease activity in ITP.

Characterization of the 5′-Flanking Region and Regulation of Transcription of Human BAFF-R Gene

“…BAFF-R appears to be the primary receptor responsible for B-cell development and survival (Thompson et al, 2001). Recent evidence (Cater et al, 2005;Hamzaoui et al, 2008;Kohno et al, 2008;Ju et al, 2009;Zhou et al, 2009) has demonstrated that BAFF-R is related to several diseases. In this study, we sought to clone and characterize the 5 0 -flanking region of human BAFF-R gene and elucidate molecular requirements of the basal transcriptional machinery controlling BAFF-R gene expression, in an attempt to provide basal evidence for further researches on the mechanism of BAFF-R transcription regulation.…”

“…Recent studies (Cater et al, 2005;Hamzaoui et al, 2008;Kohno et al, 2008;Ju et al, 2009;Zhou et al, 2009) have shown that BAFF-R has abnormal expression in autoimmune diseases, idiopathic thrombocytopenic purpura, neuro-Behçet's disease, and also in malignant cells of nonhematopoietic origins, and it is reported that BAFF and BAFF-R have abnormal expression in patients with different types of nonHodgkin's lymphomas (Briones et al, 2002;Oki et al, 2007), suggesting that BAFF-R is involved in the development of various diseases. However, these studies focused on the relationship between BAFF-R expression and diseases without clearly defining the molecular mechanism of BAFF-R genic 1 transcription.…”

The Roles of the TNF-Family Member B-Cell Activation Factor Belonging to the TNF-Family (BAFF) in Autoimmunity

“…Although serum BAFF levels were not correlated with anti-GBM antibodies titers, those levels were associated with the percentage of glomeruli with crescents. Elevated serum BAFF levels were also demonstrated in patients with Graves' disease [115], autoimmune pancreatitis [116], myasthenia gravis [117], idiopathic thrombocytopenic purpura [118] and multiple sclerosis [119].…”

Recent progress in understanding the pathogenesis of immune thrombocytopenia

“…It has been reported that BAFF is elevated in several autoimmune diseases [48]. Zhou et al [49] studied this factor in ITP and found that there were higher levels of BAFF and of BAFF mRNA in the leukocytes of patients with ITP. Another study by the same group subsequently demonstrated that BAFF may play a pathogenic role in ITP by promoting the survival of CD19þ B cells and blockade of BAFF by a decoy receptor (BR3-Fc) reduced the BAFF expression, suggesting that this type of blockade might be a promising therapy for ITP [50 ].…”