Serum Soluble TACI, a BLyS Receptor, Is a Powerful Prognostic Marker of Outcome in Chronic Lymphocytic Leukemia

Abstract

BLyS is involved in CLL biology and its low soluble serum levels related to a shorter time to first treatment (TFT). TACI is a BLyS receptor and can be shed from cells' surface and circulate in soluble form (sTACI). We investigated the impact of serum BLyS and sTACI levels at diagnosis in CLL patients and their relationship with disease parameters and patients' outcome. Serum BLyS was determined in 73 patients, while sTACI in 60. Frozen sera drawn at diagnosis were tested by ELISA. sTACI concentrations correlated with BLyS (P = −0.000021), b2-microglobulin (P = 0.005), anemia (P = −0.03), thrombocytopenia (P = 0.04), Binet stage (P = 0.02), and free light chains ratio (P = 0.0003). Soluble BLyS levels below median and sTACI values above median were related to shorter TFT (P = 0.0003 and 0.007). During a ten-year followup, sTACI levels, but not BLyS, correlated with survival (P = 0.048). In conclusion, we confirmed the prognostic significance of soluble BLyS levels with regard to TFT in CLL patients, and, more importantly, we showed for the first time that sTACI is a powerful prognostic marker, related to parameters of disease activity and staging and, more importantly, to TFT and OS.

Effect of TACI Signaling on Humoral Immunity and Autoimmune Diseases

“…Although TACI is mainly present on the cell surface, a small amount of TACI is shed from the cell surface by a disintegrin and metalloproteinase (ADAM) 10 and converted into soluble TACI (sTACI) [ 38 , 48 ]. The sTACI plasma levels are elevated in SLE, chronic lymphocytic leukemia (CLL), and CVID patients [ 49 , 50 ]. Additionally, in SLE and CLL patients, the sTACI levels are related to disease activities.…”

Analysis of serum B cell‐activating factor from the tumor necrosis factor family (BAFF) and its soluble receptors in systemic lupus erythematosus

“…All three soluble BAFF receptors have been reported in rheumatoid arthritis, 11 and sTACI and sBCMA have been described in multiple sclerosis, multiple myeloma and patients with chronic lymphocytic leukaemia. 7,8,[12][13][14] One group recently reported the presence of sBCMA and sTACI in human SLE 7,8 ; however, this was in a cohort of modest size (N < 50), and did not investigate clinical phenotypic associations, or association with flare or organ damage. To date, there are no publications on sBAFF-R in SLE.…”

MicroRNA-155-5p Overexpression in Peripheral Blood Mononuclear Cells of Chronic Lymphocytic Leukemia Patients Is a Novel, Independent Molecular Biomarker of Poor Prognosis

“…However, the bootstrapping that was performed in Cox regression strengthens the hypothesis that miR-155-5p overexpression is a promising molecular biomarker of unfavorable prognosis in CLL. Therefore, a panel of molecular prognostic biomarkers that have recently emerged—e.g., the human leukocyte antigen (HLA-G) [ 56 ], high histone deacetylase (HDAC) activity [ 57 ], mRNA expression of kallikrein-related peptidase 14 ( KLK14 ) [ 58 ] and BCL2-like 12 ( BCL2L12 ) [ 59 ], circulating miR-150 [ 60 ], SRY-box 1 (SOX1) [ 61 ], and serum soluble transmembrane activator calcium modulator and cyclophilin ligand interactor (TACI) [ 62 ]—could prove even more promising, provided that it integrates miR-155-5p expression as a new component. In support of this suggestion, it should be added that accumulation of several unfavorable prognostic markers has been proven to deteriorate prognosis in CLL [ 63 ].…”