Xiaozhou He

The Expression of B-Cell Activating Factor Belonging to Tumor Necrosis Factor Superfamily (BAFF) Significantly Correlated With C4D in Kidney Allograft Rejection

INTRODUCTION B-cell activating factor, belonging to the tumor necrosis factor (TNF) superfamily (BAFF), plays an important role in the development and survival of B lymphocytes. The present study was to investigate the correlation of BAFF and complement residue C4d in kidney allograft biopsies. METHODS Transplant kidney biopsies as allograft were studied. 10 acute rejection (AR) cases, 3 interstitial fibrosis/tubular atrophy (IF/TA) cases, and 9 unknown etiology cases from January 1, 2001 to July 20, 2007 were analyzed. Transplanted kidneys were excised because of graft loss, and their pathological sections were studied. Ten other protocol biopsy specimens were studied. These recipients who received protocol biopsies had serum creatinine levels that were within normal range (normal value: < 144 micromol/L) from 2007. [corrected] BAFF, C4d, and immunoglobulin G (IgG) were detected by immunohistochemical stain methods. All were primary renal transplant recipients. RESULTS In AR and IF/TA cases, BAFF was strongly stained, similar to C4d. And BAFF and C4d were distributed in the perinephric tubular epithelial cell cytoplasm and cytomembrane. In the unknown etiology sections and protocol biopsy sections, BAFF was weakly or not expressed, similar to C4d. In BAFF and C4d high expression sections, weak or moderate IgG deposition was also found. CONCLUSION BAFF may be associated with the development of antibody-mediated allograft rejection in kidney transplantation.

Abnormal high expression of B-cell activating factor belonging to the TNF superfamily (BAFF) associated with long-term outcome in kidney transplant recipients.

B-cell activating factor belonging to the tumor necrosis factor superfamily (BAFF) is a critical regulator of B-cell maturation and survival. We investigated the expression of BAFF in peripheral blood sample from kidney transplant recipients. Results of flow cytometry showed that at 5 years or more posttransplantation, cell-surface BAFF was significantly expressed on peripheral CD3+ T lymphocytes kidney transplant recipients in compared with other groups (P < .05). BAFF expression was noted on CD4+ and CD8+ T cells. The BAFF messenger RNA level in peripheral mononuclear cells was consistent with the protein level. However, the serum soluble BAFF level varied among individuals in each group. Stratified by renal function, the cell-surface BAFF level was significantly higher in recipients with abnormal renal function compared with those with normal renal function (P < .05). Enzyme-linked immunosorbent assay results showed that expression level of cell-surface BAFF significantly correlated with panel reactive antibody. These results indicate that BAFF may be involved in the development of graft loss.

The Abnormal High Expression of B Cell Activating Factor Belonging to TNF Superfamily (BAFF) and Its Potential Role in Kidney Transplant Recipients

B cell activating factor belonging to TNF superfamily (BAFF) is a critical regulator of B cell maturation and survival. In this present study, the expression characteristic of BAFF in kidney transplantation recipients was investigated, its potential significance was analyzed and peripheral blood of follow-up kidney transplant recipients was studied. Flow cytometric assay results showed that, cell-surface BAFF was significantly highly expressed on peripheral CD3+ T lymphocytes in ≥ 5 yrs group of kidney transplant recipients, compared with other groups (p < 0.05). BAFF expression could be found on CD4+ T cells and CD8+ T cells. The BAFF mRNA levels in peripheral mononuclear cells were consistent with the protein levels. However, serum soluble BAFF levels were interindividually different in each group. Stratified by renal function, it was found that cell-surface BAFF levels were significantly higher in those with abnormal renal function, compared with recipients with normal renal function (p < 0.05). ELISA assay results showed that expression levels of cell surface BAFF were significantly correlated with anti-HLA I & II antibodies. These results indicate that BAFF may be involved in the development of graft-loss and influences the long-time outcome of kidney allograft, likely mediated by interfering with immune response.

B-cell-activating factor code and human cytomegalovirus infection in renal transplant recipients

The objective of the present study was to explore the correlation between the BAFF signal and HCMV‐TLR activation in RTx recipients complicated by HCMV. Peripheral blood (anticoagulated by EDTA‐Na2) and urine of 113 RTx recipients were collected; healthy volunteers were controlled. Urine HCMV‐DNA was detected by real‐time PCR. Recipients were classified into a positive group (>10,000 copies/mL urine) and a negative group (<10,000 copies/mL urine). ELISA results showed that sBAFF, sera anti‐HCMV pp65 immunoglobulin (Ig)G antibody, and total IgG all significantly increased in recipients with positive HCMV‐DNA (>10,000 copies/mL urine) (P < 0.05) compared with negative recipients (<10,000 copies/mL urine). In the positive group, HCMV‐DNA copies and total IgG positively correlated with sBAFF (r = 0.988 and 0.625, respectively) (P < 0.05). Luminex assay results suggested that the incidence of anti‐HLA I and II and MICA antibody obviously increased in positive recipients. The expression level of BAFF and BAFF‐R increased in positive recipients. A total of 88 particular genes—involved in TLR signaling pathways, NF‐κB signaling pathways, and cytokine‐cytokine receptor signaling pathways—were detected in real‐time PCR chip assay. A total of 46 genes were differentially expressed greater than two‐fold, and the expression characteristic of BAFF‐R was concordant with FACS results. Our findings are that activation of HCMV would induce or enhance the activation of BAFF code in RTx recipients, which may independently or cooperatively participate in renal allograft injury and decrease the long‐term outcome of renal allografts.

Serum miR-338-5p, Soluble B-Cell–Activating Factor, Allo-Antibodies, and Renal Transplantation

BACKGROUND The objective of the study was to explore the expression features of serum miR-338-5p and soluble B-cell-activating factor (sBAFF) in renal transplant recipients. METHODS Follow-up renal transplant recipients (n = 49) were enrolled in this study (male/female: 38/11). Healthy volunteers were controlled; 2 mL of peripheral blood from each subject was collected. Total RNA was extracted from serum by use of the miRNeasy Serum/Plasma Kit (QIAGEN), and miR-338-5p was amplified by means of quantitative real-time reverse transcriptase-polymerase chain reaction. sBAFF was detected by means of enzyme-linked immunoassay. LABScreen Mix (LSM12) (One Lambda) was used to test the level of anti-human leukocyte antigen (HLA) I antibody (Ab), anti-HLA II Ab, and anti-major histocompatibility complex class I chain-related A (MICA) Ab. All data are shown as mean ± SD and were analyzed by use of SPSS software 17.0. RESULTS Compared with healthy volunteers, serum miR-338-5p in recipients was statistically downregulated (2.79 ± 2.5 versus 0.09 ± 0.12, P < .001); sBAFF in recipients was significantly upregulated (1321 ± 950 pg/mL versus 534 ± 327 pg/mL, P < .01); serum anti-HLAII Ab, anti-MICA Ab, and anti-HLA+MICA Abs all statistically increased in recipients (P < .05). Spearman correlation analysis showed that miR-338-5p was significantly negatively correlated with sBAFF (r = -0.51, P < .001) and anti-HLA II antibody with mean fluorescence intensity value >1000 (r = -0.322, P < .05). Analysis results also suggested that sBAFF was significantly negatively correlated with anti-MICA Ab, with mean fluorescence intensity value >1000 (r = -0.579, P < .05). CONCLUSIONS miR-338-5p is closely correlated with the procedure of renal allograft antibody-mediated rejection.