Relationship between Circulating BAFF Serum Levels with Proliferating Markers in Patients with Multiple Myeloma

Alexandrakis, Michael G.; Roussou, Parascevi; Pappa, Constantina A.; Messaritakis, Ippokratis; Xekalou, Athina; Goulidaki, Nektaria; Boula, Anna; Tsirakis, George

doi:10.1155/2013/389579

Cited by 19 publications

(14 citation statements)

References 33 publications

(38 reference statements)

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“…In addition, a significant positive correlation between BAFF and IL-10 was found only for this subset of the CVID patients (Figure 3). Similar data were previously reported for immunoinflammatory and lymphoproliferative diseases such as active sarcoidosis, multiple myeloma and chronic lymphocytic leukemia, possibly through the induction of IL-10 production by transitional B cells [27][28][29] .…”

Section: Ai -Autoimmune Diseases; Pd -Pulmonary Diseases; Ri -Recurresupporting

confidence: 88%

Serum B cell activating factor and interleukin 10 levels in common variable immunodeficiency: Relationship with clinical findings

Mijanovic

Andrejević²,

Jurišić

et al. 2019

VOJNOSANIT PREGL

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Background/Aim. Common variable immunodeficiency (CVID) is an immunologically and clinically heterogeneous disorder. Disturbed cytokine production is implicated in dysfunctional immune response. The aim of this study was to investigated B-cell activating factor (BAFF) and interleukin (IL)- 10 levels in CVID patients. Methods. The study included 28 CVID patients diagnosed and followed during a 20-year period (mean follow-up 14.5 years). Control groups consisted of 4 patients with X-linked agammaglobulinemia (XLA) and 21 healthy subjects. According to clinical characteristics, the CVID patients were divided into four groups which partly overlap: chronic pulmonary diseases (n = 21), splenomegaly (n = 13), autoimmune diseases (n = 9) and patients with recurrent infections despite regular intravenous immunoglobulin (IVIg) substitution (n = 4). The serum levels of BAFF and IL-10 were measured by commercial ELISA. Results. The BAFF levels were found to be higher in all CVID patients compared to the healthy controls (p < 0.01). The most significant differences were observed in the patients with pulmonary diseases and splenomegaly (p < 0.0001). Also, concentrations of IL-10 were higher in all CVID patients in comparison with the XLA patients (p < 0.05) and healthy subjects (p < 0.01). A statistically significant positive correlation (r = 0.86; p < 0.01) was found between the levels of BAFF and IL-10 in the CVID patients with autoimmune diseases. We demonstrated that the CVID patients with chronic pulmonary diseases had higher levels of IL-10, while the CVID patients with recurrent infections had higher BAFF concentrations in comparison to the patients without these features (p < 0.05). Conclusion. In spite of the limited number of patients, this is the first report from Serbia, examining the serum levels of BAFF and IL-10 in the CVID patients. Our study showed significantly increased concentrations of serum BAFF and IL-10 in the patients with CVID compared to the healthy subjects. Further studies are needed to confirm our findings that the BAFF levels are more pronounced in patients with recurrent infections while IL-10 levels are higher in patients with chronic pulmonary diseases. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175065]

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Section: Ai -Autoimmune Diseases; Pd -Pulmonary Diseases; Ri -Recurresupporting

confidence: 88%

Serum B cell activating factor and interleukin 10 levels in common variable immunodeficiency: Relationship with clinical findings

Mijanovic

Andrejević²,

Jurišić

et al. 2019

VOJNOSANIT PREGL

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“…Additionally, BAFF serum levels correlate positively with markers for angiogenesis (TNF-α, VEGF, microvessel density), 63 , 64 BM infiltration 38 , 66 and proliferation (proliferating cell nuclear antigen and Ki-67 staining). 62 , 66 Of further interest, several authors have established an inverse correlation between circulating BAFF and progression-free survival 65 and overall survival. 62 , 63 These findings clearly establish a clinically relevant link between BAFF and MM and have prompted multiple authors to suggest BAFF as a possible biomarker for tumor burden, disease progression and prognosis and as a potential target for therapy.…”

Section: The Role Of Baff In the Pathophysiology Of MMmentioning

confidence: 94%

“… 10 , 40 , 44 , 61 , 62 , 63 , 64 , 65 , 66 , 67 Furthermore, BAFF serum levels correlate positively with a diverse spectrum of established progression markers in MM including several ILs (IL-6, -10 and -15), lactic dehydrogenase, C-reactive protein and beta-2-microglobulin. Additionally, BAFF serum levels correlate positively with markers for angiogenesis (TNF-α, VEGF, microvessel density), 63 , 64 BM infiltration 38 , 66 and proliferation (proliferating cell nuclear antigen and Ki-67 staining). 62 , 66 Of further interest, several authors have established an inverse correlation between circulating BAFF and progression-free survival 65 and overall survival.…”

Section: The Role Of Baff In the Pathophysiology Of MMmentioning

confidence: 99%

B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?

Hengeveld

Kersten

2015

Blood Cancer Journal

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Multiple myeloma (MM) is a currently incurable malignancy of plasma cells. Malignant myeloma cells (MMCs) are heavily dependent upon the bone marrow (BM) microenvironment for their survival. One component of this tumor microenvironment, B-Cell Activating Factor (BAFF), has been implicated as a key player in this interaction. This review discusses the role of BAFF in the pathophysiology of MM, and the potential of BAFF-inhibitory therapy for the treatment of MM. Multiple studies have shown that BAFF functions as a survival factor for MMCs. Furthermore, MMCs express several BAFF-binding receptors. Of these, only Transmembrane Activator and CAML Interactor (TACI) correlates with the MMC's capability to ligate BAFF. Additionally, the level of expression of TACI correlates with the level of the MMC's BM dependency. Ligation of BAFF receptors on MMCs causes activation of the Nuclear Factor of κ-B (NF-κB) pathway, a crucial pathway for the pathogenesis of many B-cell malignancies. Serum BAFF levels are significantly elevated in MM patients when compared to healthy controls, and correlate inversely with overall survival. BAFF signaling is thus an interesting target for the treatment of MM. Several BAFF-inhibitory drugs are currently under evaluation for the treatment of MM. These include BAFF-monoclonal antibodies (tabalumab) and antibody-drug conjugates (GSK2857916).

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“…These findings have led to the development of novel mAbs that target both BAFF and APRIL (e.g., atacicept), as well as those that target BCMA, for the treatment of multiple myeloma (Rossi, ; Carpenter et al , ; Tai & Anderson, ). Another limitation is that we did not investigate the potential role of other cytokines, such as IL6, which promotes multiple myeloma cell growth and is thought to be involved in the development of drug resistance (Lauta, ; Alexandrakis et al , ). Another potential explanation for lack of efficacy of tabalumab involves the BAFF receptor Transmembrane Activator and CAML Interactor (TACI, TNFRSF13B).…”

Section: Discussionmentioning

confidence: 99%

Phase 2 study of tabalumab, a human anti‐B‐cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma

Raje

Moreau²,

Terpos

et al. 2016

Br J Haematol

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In this double-blind, Phase 2 study, 220 patients with relapsed/refractory multiple myeloma were randomly assigned 1:1:1 to receive placebo (N = 72), tabalumab 100 mg (N = 74), or tabalumab 300 mg (N = 74), each in combination with dexamethasone 20 mg and subcutaneous bortezomib 1·3 mg/m on a 21-day cycle. No significant intergroup differences were observed among primary (median progression-free survival [mPFS]) or secondary efficacy outcomes. The mPFS was 6·6, 7·5 and 7·6 months for the tabalumab 100, 300 mg and placebo groups, respectively (tabalumab 100 mg vs. placebo Hazard ratio (HR) [95% confidence interval (CI)] = 1·13 [0·80-1·59], P = 0·480; tabalumab 300 mg vs. placebo HR [95% CI] = 1·03 [0·72-1·45], P = 0·884). The most commonly-reported treatment-emergent adverse events were thrombocytopenia (37%), fatigue (37%), diarrhoea (35%) and constipation (32%). Across treatments, patients with low baseline BAFF (also termed TNFSF13B) expression (n = 162) had significantly longer mPFS than those with high BAFF expression (n = 55), using the 75th percentile cut-off point (mPFS [95% CI] = 8·3 [7·0-9·3] months vs. 5·8 [3·7-6·6] months; HR [95% CI] = 1·59 [1·11-2·29], P = 0·015). Although generally well tolerated, PFS was not improved during treatment with tabalumab compared to placebo. A higher dose of 300 mg tabalumab did not improve efficacy compared to the 100 mg dose. Nonetheless, BAFF appears to have some prognostic value in patients with multiple myeloma.

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Relationship between Circulating BAFF Serum Levels with Proliferating Markers in Patients with Multiple Myeloma

Cited by 19 publications

References 33 publications

Serum B cell activating factor and interleukin 10 levels in common variable immunodeficiency: Relationship with clinical findings

Serum B cell activating factor and interleukin 10 levels in common variable immunodeficiency: Relationship with clinical findings

B-cell activating factor in the pathophysiology of multiple myeloma: a target for therapy?

Phase 2 study of tabalumab, a human anti‐B‐cell activating factor antibody, with bortezomib and dexamethasone in patients with previously treated multiple myeloma

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