The Association between the Circulating B-cell Activating Factor Serum Level and B-cell Chronic Lymphocytic Leukemia

Abstract

B-cell chronic lymphocytic leukemia (B-CLL) constitutes the most prevalent leukemia in Western countries,and it is an incurable disease characterized by extensive clinical heterogeneity despite a common diagnostic immunophenotype [small mature B cells display CD19+, CD20+, CD5+, CD23 markers]. Whether defects in the apoptotic pathway are frequently encountered in a variety of cancers, B-CLL represents a paradigm of the tumors that arise as a consequence of alterations in the processes leading to programmed cell death Indeed, B-CLL cells display multiple intrinsic defects in their apoptotic machinery and dysregulated production of survival signals from their microenvironment. Therefore, their accumulation mostly results from a deficient apoptosis rather than from an acute proliferation B-cell activating factor (BAFF) is a molecule that identified by sequence homology with the TNF superfamily members, also named BLyS (B-lymphocyte stimulator) because it induces B lymphocyte proliferation and immunoglobulin secretion. BAFF and its receptor play a key role in the survival and differentiation of B cells. They therefore provide not only a new insight into the development of autoreactive B cells, but also a paradigm to the interaction between survival, growth and death affecting all cells.

The aim of this work was to investigate the association between the circulating BAFF serum level and B-cell Chronic Lymphocytic Leukemia by ELISA technique. In the present study B-cell activating factor of the tumor necrosis factor family (BAFF) was measured in the serum of patients with B-cell chronic lymphocytic leukemia (B-CLL) and was correlated with clinical stages according to Binet clinical staging system. The study included 65 subjects that grouped into: group І: 25 patients diagnosed as B-cell chronic lymphocytic leukemia (B-CLL) who further classified according to Binet clinical staging system into three stages (A, B and C) and compared in there clinical features and laboratory investigation including BAFF values and group П: 40 healthy control subjects. BAFF concentrations were measured in serum of both groups using a commercially available enzyme-linked immuno-sorbent assay (ELISA) kit. The serum BAFF levels was significantly lower in the sera of B-CLL patients (211.56 ± 131.7pg/ml) compared to healthy controls (628 ± 152.6pg/ml) with (P<0.001). As regard correlation of BAFF values and laboratory data among patients there was significant positive correlation between BAFF values versus Hb level, platelet count and CD5(P = 0.004, 0.015 and 0.002 respectively). While there was significant inverse correlation between BAFF values versus TLC, BM infiltration and sIgM (P = 0.013, 0.008 and 0.033 respectively). Furthermore, we found that BAFF level was significant lower in stage C than stage B and A, as mean± SD was (127.18 ±83.08, 256.5 ± 125.5 and 331.2 ± 128.47 pg/ml respectively) with P = 0.006, indicating that BAFF level decreases with advanced stages of B-CLL. In order to predict B-CLL, the (ROC) curve was performed and identified that 425 pg/ml was the best cut off value of serum BAFF level with sensitivity 96% and specificity 92.5%, so when its level below or equal 425 pg/ml we can predict B-CLL cases while if above 425 pg/ml we can rule out the disease. From our study, BAFF is considered a valid predictive marker for B-CLL cases.