Enumeration of interleukin-10-positive B cells from peripheral blood of patients with chronic lymphocytic leukemia

Rossi, Marco; Gentile, Massimo; Toscano, Rosa; Recchia, Anna Grazia; Bossio, Sabrina; Caruso, Nadia; Stefano, Laura De; Granata, Teresa; Pellicanò, Mariavaleria; Vigna, Ernesto; Tagliaferri, Pierosandro; Tassone, Pierfrancesco; Morabito, Fortunato

doi:10.3109/10428194.2013.824078

Cited by 5 publications

(3 citation statements)

References 8 publications

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“…46,47 Finally, CLL cells have features similar to those of regulatory B cells, producing IL-10 which has immunosuppressive properties. 48,49 Interestingly, IL-10 production has been shown to be greater in IGHV-mutated cells than in unmutated cells as a result of reduced DNA methylation. 49 Plasma levels of IL-10 are similar in IGHV-mutated and unmutated disease, possibly reflecting the greater tumor burden with unmutated disease.…”

Section: Discussionmentioning

confidence: 99%

IgA levels at diagnosis predict for infections, time to treatment, and survival in chronic lymphocytic leukemia

Ishdorj

Streu²,

Lambert

et al. 2019

Blood Advances

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To better understand the relationship between baseline immunoglobulin measurements and subsequent clinical outcomes in chronic lymphocytic leukemia (CLL), we performed a retrospective analysis on 660 patients with CLL (72%), monoclonal B-cell lymphocytosis (MBL) (13%), and small lymphocytic lymphoma (SLL) (14%), diagnosed between 2005 and 2014 at CancerCare Manitoba. Of 511 patients who had their first immunoglobulin level determined within 3 months of diagnosis, abnormal (either increased or decreased) immunoglobulin M (IgM), IgG, and IgA values were observed in 58% of patients with CLL, 27% of patients with MBL, and 20% of patients with SLL. Immunoglobulin deviances were similar for MBL and CLL Rai stage 0 and for SLL and Rai stages I and II; for CLL, IgG and IgA abnormalities occurred with increasing frequency with advancing Rai stage. In contrast, the frequency of IgM abnormalities was similar in all patient groups. IgA abnormalities significantly correlated with high β2-microglobulin (B2M) expression, whereas abnormal IgG and IgA levels were associated with the use of IGHV1-69, 3-21, and 3-49 subtypes. Increases in IgG or IgM were commonly associated with the presence of a CLL-type M-band, whereas oligoclonal bands were frequently observed with increased IgA levels. Although abnormal levels of IgG and IgA at diagnosis were independent predictors for future immunoglobulin replacement, only abnormal IgA levels were associated with shorter time to first treatment and overall survival. These findings indicate that both reduced and elevated levels of IgG and IgA at diagnosis are important and independent prognostic markers for infection in CLL, with IgA being more relevant as a marker of disease progression and survival.

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Section: Discussionmentioning

confidence: 99%

IgA levels at diagnosis predict for infections, time to treatment, and survival in chronic lymphocytic leukemia

Ishdorj

Streu²,

Lambert

et al. 2019

Blood Advances

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“…24 In addition, the typical Breg markers of CD5, CD24, and CD27 are all defined within the typical phenotype of CLL (Table 1). 24,62 Finally, although they spontaneously release modest amounts during circulation, 84 CLL cells produce significant amounts of IL-10 after stimulation by a range of stimuli, including microbial products (eg, CpG-ODN, LPS), T-cell costimulation (via CD40L or IL4), or B cell-activating factor of the tumor necrosis factor family (BAFF) from monocyte/macrophages in vitro (Figure 4). 24 Although these stimuli may not be operating in vivo, IL-10 transcript is upregulated within CLL cells of the lymph node, 69 and STAT3, a potent mediator of IL-10-driven antiinflammatory signaling, 85 is also phosphorylated in the tissues of CLL patients.…”

Section: Role Of Cll Cells In Mediating Immune Suppression: the Tumormentioning

confidence: 99%

Perturbation of the normal immune system in patients with CLL

Forconi

Moss

2015

Blood

324

314

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Immune dysregulation is a cardinal feature of chronic lymphocytic leukemia (CLL) from its early stage and worsens during clinical observation, even in absence of disease progression. Although the mechanisms remain unclear, new insights are emerging into the complex relationship between the CLL clone and its immune environment. T cells are increased in early-stage disease and show progressive accumulation and exhaustion. The mechanisms that drive this expansion may include auto-antigens involved in the original clonal expansion. In addition, chronic viral infections such as cytomegalovirus generate huge virus-specific immune responses, which are further expanded in CLL. Attention is now focused largely on the direct immunosuppressive properties of the tumor. Remarkably, CLL clones often have features of the recently described regulatory B cells producing immunosuppressive IL-10. Better knowledge of the regulatory properties intrinsic to CLL cells may soon become more important with the switch from chemotherapy-based treatments, which trade control of CLL with further impairment of immune function, to the new agents targeting CLL B-cell receptor-associated signaling. Treatment with these new agents is associated with evidence of immune recovery and reduced infectious complications. As such, they offer the prospect of immunologic rehabilitation and a platform from which to ultimately replace chemotherapy

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“…18,26 They also share physiological analogies. While non-stimulated CLL cells produce low levels of IL-10, 27 in vitro stimulation through CD40L or TLR9 induces significant production of IL-10, 25 similar to human Breg cells. 9,17,22 Furthermore, the inability of CLL B cells to stimulate T cell proliferation or their Th1 polarization 28 associated with increased Treg frequencies 29 suggest that they could exhibit regulatory properties like Breg cells inhibiting the T cell proliferation through an IL-10-independent mechanism, 22,30 suppressing the Th1 polarization through the production of IL-10 20 and expanding the Treg cells.…”

Section: Introductionmentioning

confidence: 95%

The regulatory capacity of B cells directs the aggressiveness of CLL

et al. 2018

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Chronic lymphocytic leukemia (CLL) is associated with abnormal T-cell responses responsible for defective anti-tumor activities. Intriguingly, CLL B cells share phenotypical characteristics with regulatory B (Breg) cells suggesting that they might negatively control the T-cell activation and immune responses. We elaborated an in vitro co-culture system with T cells to evaluate the Breg capacities of CLL B cells following innate Toll-like receptor 9 (TLR9) engagement. We demonstrated that B cells from half of the patients exhibited regulatory capacities, whilst B cells from the remaining patients were unable to develop a Breg function. The T cell sensitivities of all patients were normal suggesting that defective Breg activities were due to intrinsic CLL B cell deficiencies. Thus, TLR-dedicated gene assays highlighted differential signature of the TLR9 negative regulation pathway between the two groups of patients. Furthermore, correlations of the doubling time of lymphocytosis, the time to first treatment, the mutational status of IgVH and the Breg functions indicate that patients with efficient Breg activities have more aggressive CLL than patients with defective Breg cells. Our in vitro observations may open new approaches for adjusting therapeutic strategies targeting the Breg along with the evolution of the disease.

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Enumeration of interleukin-10-positive B cells from peripheral blood of patients with chronic lymphocytic leukemia

Cited by 5 publications

References 8 publications

IgA levels at diagnosis predict for infections, time to treatment, and survival in chronic lymphocytic leukemia

IgA levels at diagnosis predict for infections, time to treatment, and survival in chronic lymphocytic leukemia

Perturbation of the normal immune system in patients with CLL

The regulatory capacity of B cells directs the aggressiveness of CLL

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