Dynamics of TREC and KREC for patients after therapy with anti-CD20 monoclonal antibodies
0
Citation
0
Reference
10
Related Paper
Keywords:
Immunophenotyping
Antibodies to CD20 have confirmed the hypothesis that monoclonal reagents can be given in vivo to alleviate human diseases. The targeting of CD20 on normal, malignant and auto-immune B-lymphocytes by rituximab has demonstrated substantial benefits for patients with a variety of B-cell lymphomas, as well as some with autoimmune disorders. There has been a notable increase in the survival rates from B-cell lymphoma in the decade since anti-CD20 therapy was introduced.
Monoclonal antibody therapy
Cite
Citations (240)
Ocrelizumab
Cite
Citations (130)
[Analysis of immunophenotype characteristics in 109 cases of B lineage chronic B lymphoid leukemia].
This study was aimed to investigate the immunophenotypic characteristics of 109 cases of B-cell chronic lymphoid leukemia (B-CLL) so as to provide evidences for the diagnosis and therapy of B-CLL, and for the detection of the minimal residual disease and its prognosis. Immunophenotyping was performed in 109 patients of B-CLL by two/three color multiparameter flow cytometry analysis using a panel of monoclonal antibodies. The results showed that in 109 cases of B-CLL, all cases expressed CD19, the positive ratios of other B lineage antigen such as CD20, CD22 and CD23 were 95.40%, 94.50%, 86.20% respectively. None of the B-CLL cases expressed CD10. The expression ratio of FMC-7 and CD38 in 105 cases of B-CLL were 28.60% and 36.20%. Among the B-CLL cases the CD5(+) cells amounted to 86.23%, CD5(-) cells amounted to 13.76%, ZAP-70 protein was expressed in 12 out of 50 patients. It is concluded that immunophenotypic data are very useful for the diagnosis and detection of minimal residual disease of B-CLL, and the relationship between the immunophenotypic characteristics and the prognosis of B-CLL needs further study.
Immunophenotyping
CD5
CD23
Minimal Residual Disease
Cite
Citations (0)
To identify potential alternatives to Epstein-Barr virus (EBV)-specific cytotoxic T-cell responses, peripheral lymphocyte subsets (PLS) (CD4+, CD8+, CD3+, CD19+, CD56+) were measured by flow cytometry in children with abdominal transplants (n = 22) and heart transplants (n = 2), with (n = 14) and without (n = 10, group C) post-transplant lymphoproliferative disorder (PTLD). PTLD resolved with reduced immunosuppression and antiviral therapy in eight children (group B). Recalcitrant PTLD was observed in six children (group A). Recalcitrant PTLD followed prior antilymphocyte therapy [monoclonal anti-CD3 antibody (OKT3) and thymoglobin (n = 3) and thymoglobin (n = 1)] for refractory rejection in four of these six children, and resolved after treatment with rituximab (anti-CD20 monoclonal antibody). Ten children without PTLD served as a control group (group C). Between group comparisons showed a numeric increase in CD8 + cells and significantly lower CD4:CD8 ratios in both PTLD groups (A and B) compared with group C. Group A children also demonstrated significant depletion of natural killer (NK) cells, and post-rituximab depletion of B-cells compared with group B (no rituximab treatment). We conclude that NK cell depletion with a reversed CD4:CD8 ratio may represent a persistent immunosuppressed state, which may result from prior antilymphocyte therapy and may predispose to recalcitrant EBV-PTLD. Clinical remission with rituximab is accompanied by B-cell depletion. Serial monitoring of PLS from the time of diagnosis of PTLD will be necessary to confirm these observations.
Immunosuppression
Post-transplant lymphoproliferative disorder
Lymphoproliferative Disorders
Cite
Citations (10)
To investigate key factors that may contribute to the variability of rituximab-mediated peripheral and renal B cell depletion (BCD) in SLE.
Obinutuzumab
Belimumab
Cite
Citations (19)
Xenotransplantation
Cite
Citations (12)
Anti-CD20 therapy using rituximab directly targeting B cells has been approved for treatment of non-Hodgkin lymphoma, rheumatoid arthritis and anti-neutrophil cytoplasmic antibody-associated vasculitides and has led to reappreciation of B-lineage cells for anti-rheumatic treatment strategies. Moreover, blocking B-cell activating factor with belimumab, a drug that is licensed for treatment of active, seropositive systemic lupus erythematosus (SLE), represents an alternative, indirect anti-B-cell approach interfering with proper B-cell development. While these approaches apparently have no substantial impact on antibody-secreting plasma cells, challenges to improve the treatment of difficult-to-treat patients with SLE remain. In this context, anti-CD19 antibodies have the promise to directly target autoantibody-secreting plasmablasts and plasma cells as well as early B-cell differentiation stages not covered by anti-CD20 therapy. Currently known distinct expression profiles of CD19 by human plasma cell subsets, experiences with anti-CD19 therapies in malignant conditions as well as the rationale of targeting autoreactive plasma cells in patients with SLE are discussed in this review.
Belimumab
Cite
Citations (98)
To assess the presence and phenotype of B-lineage cells in the bone marrow (BM) of rheumatoid arthritis (RA) patients after rituximab therapy.Six patients were studied. BM aspirates were collected 3 months after the treatment and analysed using the four-colour flow cytometry.CD19+ (B-lineage) cells in BM samples varied from 0.1 to 3.25% in the lymphoid gate. CD34+ cells varied from 1.23 to 4.86%. The proportion of CD34+ cells committed to the B-lineage varied between 0 and 42.19%. Pro-B-cells were undetectable in one case. The majority of B-cell precursors were pro-B-cells in Patients 5 and 6 (50 and 62% of CD19+ cells, respectively), pre-B-cells in Patients 3 and 4 (64 and 70%) and immature B-cells in Patient 1 (44%). Detectable CD20 expression on CD19+ cells was either low or absent. Plasma cells varied from 0.01 to 0.36% of the total nucleated cells. There was a trend towards longer duration of clinical response in patients with evidence of more complete depletion in BM.In this small cohort of RA patients treated with rituximab, differences in proportion and phenotype of CD19+ BM cells were detected. These differences suggest variation in the degree of depletion achieved and correlate with time to relapse. Although pro-B-cells are not targeted directly by rituximab as they do not express CD20, the levels were unexpectedly low.
Immunophenotyping
CD5
Cite
Citations (95)
Background CD19 is a membrane glycoprotein interacting with different surface molecules like the B cell receptor (BCR) and is crucial for antigen-independent development as well as immunoglobulin-induced activation of B cells.[1] Alterations in this signalling pathway can incline autoantibody production and systemic autoimmunity in humans. Rituximab (RTX), a CD20 antagonist appears to be an effective candidate in the treatment of different autoimmune diseases that are partly driven by autoreactive B cells, such as systemic sclerosis (SSc).[2] It has been speculated that RTX might work not only by depleting B cells but also to down regulate activation markers, such as CD19. Objectives In-depth analysis of CD19 abundancy and activation on B cells in SSc patients with and without RTX treatment Methods Peripheral blood samples from 41 patients suffering from SSc (median ± standard deviation SD, age: 54.3 ± 10.6 years, female ratio: 0.8) and 45 age- and sex-matched healthy controls (HC) (age: 51.0 ± 13.9 years, female ratio: 0.8) were drawn and PBMCs were isolated on-site. We performed flow cytometry analysis on a standardized BD LSRFortessa platform to identify B cell (CD19+CD20+) subpopulations. The geometric mean fluorescence intensity (gMFI) for CD19 in all B cell subtypes was extracted from the data set and used for further statistical analysis. Additionally, a quantitative flow cytometric bead-based assay (QuantiBRITE PE kit from Becton Dickinson) was used for the estimation of CD19 antibodies bound per cell. Results 3 out of 41 SSc patients were in high disease activity at the time of blood drawal. 23 SSc patients were under RTX therapy of whom 5 patients still displayed measurable B cells frequencies. Naïve B cells made up the most abundant B cell population in SSc patients. Thus, the frequency of IgM+/IgD+/CD27- B cells was 67.9% ±13.2 (mean ±SD), followed by class-switched memory B cells (IgM-/IgD-/CD27+, 10.5 ± 4.9), non-switched memory B cells (IgM+/IgD+/CD27+, 4.0 ± 3.6) and plasmablasts (0.3 ± 4.4). Pairwise Wilcoxon Tests (Bonferroni-corrected for multiple testing) showed significant differences (p < 0.001) between frequencies of naïve B cells and all other cell types. In contrast, naïve B cells displayed the second lowest CD19 gMFI levels (7601.0 ± 1912.0) in the dataset. Non-switched memory B cells in SSc patients showed the highest CD19 gMFI (10620.0 ± 15689.8), followed by class-switched (9388 ± 3048.6). As expected, Plasmablasts displayed the lowest CD19 gMFI levels (4799.0 ± 4185.7). The decrease in CD19 gMFI was again highly significant. This trajectory in decreasing CD19 gMFI was found in both HCs and SSc patients. We saw a significant reduction in percentages of non-switch B cells and class-switched B cells in SSc patients compared to HCs (4.0 ± 3.6 vs 6.5 ± 4.2, p = 0.029, 10.5 ± 4.9 vs 13.2 ± 7.2 p = 0.04) but an increase in CD19 gMFI in non-switched B cells (HC: 9204.5 ± 2116.8, p = 0.05). Interestingly, SSc patients under RTX treatment had significantly lower class-switched memory B cell frequencies compared to HCs (6.4 ± 4.2 vs. 13.2 ± 7.2, p = 0.015). However, RTX did not affect CD19 gMFI or bound CD19 in SSc. Conclusion RTX treatment in SSc is not associated with downregulation of the co-stimulation marker CD19. Thus, the main effect of this drug is the reduction of B cells, especially class-swtched memory B cells that might have a high capacity to activate other cells involved in the pathogenesis of SSc. References [1]M. Wang et al. , “Identification and Validation of Predictive Biomarkers to CD19- and BCMA-Specific CAR T-Cell Responses in CAR T-Cell Precursors,” Blood , vol. 134, no. Supplement_1, pp. 622–622, Nov. 2019, doi: 10.1182/blood-2019-122513. [2]S. Ebata et al. , “Safety and efficacy of rituximab in systemic sclerosis (DESIRES): a double-blind, investigator-initiated, randomised, placebo-controlled trial,” Lancet Rheumatol. , 2021. Acknowledgements This work was funded by a grant from JDRF, LRA and NMSS (grant key: 2-SRA-2021-1043-S-B) and the Austrian Federal Government within the COMET K1 Centre Program, Land Steiermark and Land Wien. Disclosure of Interests Barbara Dreo: None declared, Barbara Prietl: None declared, Selina Kofler: None declared, Verena Pfeifer: None declared, Harald Sourij: None declared, Florentine Moazedi-Fürst: None declared, Sonja Kielhauser: None declared, Monica D’Orazio: None declared, Sabine Zenz: None declared, Jens Thiel Speakers bureau: Novartis, GSK, Vifor, BMS, Consultant of: Novartis, GSK, Vifor, Grant/research support from: BMS, Martin Stradner: None declared, Hans-Peter Brezinsek: None declared
Immunophenotyping
CD22
Cite
Citations (0)