scholarly journals B cell depletion treatment decreases Th17 cells in patients with rheumatoid arthritis

2021 ◽  
Author(s):  
Constantina A. Bounia ◽  
Stamatis-Nick C Liossis
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
B Cell ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Treg Cells ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Das28 Score ◽  
Autoimmune Rheumatic Diseases

Abstract Introduction: We aimed to evaluate for any possible effects of treatment with rituximab (RTX) on the peripheral Th17 and Treg subpopulations in patients with rheumatoid arthritis (RA).Patients and methods: We analyzed 16 patients with RA initiating RTX treatment, 11 patients with RA initiating abatacept treatment, 11 patients with RA treated with other medications, 8 patients with other autoimmune rheumatic diseases initiating RTX, and 14 healthy volunteers. Th17 cells (CD4+IL23R+IL17A+) and Treg cells (CD4+CD25hiFoxP3+) were evaluated flow-cytometrically.Results: Th17 cells from patients treated with RTX decreased significantly at weeks 8 and 16 (mean ± SEΜ: 3.01% ± 0.54℅ CD4+ cells at week 0 vs. 1.53% ± 0.24℅ at week 8 vs 1.10% ± 0.20℅ at week 16, p = 0.0004). Reductions of Th17 cells were evident in:clinical responders (DAS28 score ≤ 3.2), ACPA (+) and RF (-) patients; circulating Tregs remained stable. Th17 and Tregs were not affected by ABA treatment or by changes in disease activity. Tregs, but not Th17 cells, decreased following treatment with RTX in patients with other autoimmune diseases (0.75% ± 0.16% at week 0 vs. 0.43% ± 0.16% at week 8, p = 0.033).Conclusion: RTX-induced B cell depletion results in a significant reduction of circulating Th17 cell percentages, whereas it has no effect on Tregs of patients with RA. This reduction of Th17 cells was evident particularly in responders to RTX treatment, ACPA+ and RF (-) patients with RA.

scholarly journals Longterm Effects of Rituximab on B Cell Counts and Autoantibody Production in Rheumatoid Arthritis: Use of High-sensitivity Flow Cytometry for More Sensitive Assessment of B Cell Depletion

2013 ◽  
Vol 40 (5) ◽  
pp. 565-571 ◽  
Author(s):  
Andrea Váncsa ◽  
Zoltán Szabó ◽  
Szilvia Szamosi ◽  
Nóra Bodnár ◽  
Edit Végh ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Flow Cytometry ◽  
Disease Activity ◽  
B Cell ◽  
Clinical Response ◽  
High Sensitivity ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Autoantibody Production ◽  
Cell Numbers

Objective.To assess the efficacy and safety of longterm rituximab (RTX) therapy for rheumatoid arthritis (RA) and study correlations among B cell depletion, clinical response, and autoantibody production.Methods.Seventy-seven patients with moderate or high RA activity received RTX and were re-treated every 6 months regardless of clinical response. All patients received at least 5 cycles. We assessed 28-joint Disease Activity Score (DAS28), IgM rheumatoid factor (RF), and anticitrullinated protein antibody (ACPA) levels at baseline, after 15 days, and then every 6 months for 24 months. Absolute CD19+ B lymphocyte counts were determined in 50 patients using high-sensitivity flow cytometry (hsFACS) by reading 100,000 events.Results.After 6, 12, 18, and 24 months, 51.6%, 51.9%, 73.3%, and 83.8% of patients, respectively, showed good European League Against Rheumatism responses. Significant and sustained decreases in IgM RF and ACPA levels were observed as early as 6 months and 12 months, respectively. The baseline mean absolute B cell number was 0.234 g/l. B cell numbers diminished significantly after the very first infusion by Day 15 (0.104 g/l; p = 0.007); they further decreased until 24 months (0.0013 g/l; p < 0.001). One RTX infusion resulted in incomplete depletion in 76.7% of patients. Upon RTX treatment, changes in CD19+ B cell numbers positively correlated with changes in DAS28 (r = 0.963, p = 0.008) and IgM RF (r = 0.859, p = 0.028), but not with changes in ACPA production (r = 0.726, p = 0.102). The correlations between B cell numbers and DAS28 were observed in both ACPA-seropositive (r = 0.999, p < 0.0001) and ACPA-negative patient subpopulations (r = 0.962, p = 0.009). The correlation between CD19+ cell numbers and IgM RF was observed only in the ACPA-positive population (r = 0.944, p = 0.005) but not in seronegative patients (r = 0.398, p = 0.435). No safety issues arose.Conclusion.In RA, clinical response to RTX is associated with the extent of B cell depletion and with autoantibody production. Changes in CD19+ B cell numbers correlate with those in disease activity and, in seropositive patients, also with IgM RF, but not with ACPA production. We found that hsFACS may be a useful method to more accurately assess incomplete B cell depletion.

scholarly journals AB0223 MODIFIED DOSE RITUXIMAB BIOSIMILAR IN RHEUMATOID ARTHRITIS COMPARING B-CELL DEPLETION EFFECT AND DISEASE ACTIVITY SCORES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1137.2-1138
Author(s):  
S. Bandyopadhyay
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
B Cell ◽  
Low Dose ◽  
Outcome Measurement ◽  
Eligible Patient ◽  
Cell Depletion ◽  
Individual Choice ◽  
B Cell Depletion ◽  
Eular Response

Background:In emerging economies self-funding patients opt for less costly options, influencing both compliance and maintenance of treatment for chronic illness. Studies comparing originator rituximab 1000mgx2 and 500mgx2 doses in Rheumatoid arthritis (RA) have yielded interesting results1. Evidence of B cell depletion, measured by CD19 count, maybe a marker for disease improvement2. However effect of different dose of biosimilar Rituximab (bRTX) on B cell depletion and disease activity needs exploration.Objectives:To determine correlation of CD19 count defining B cell depletion and disease activity with different dosages of bRTX treatment.Methods:Between April 2019 and March 2020, all RA patients with DMARD failure were screened for eligibility of biologics as routine clinical practice. Depending on individual choice, after full consent, patients received either 1000mgx2 or 500mgx2 bRTX. All patients had CD19 count before and 12 months after the first dose. Effectiveness of bRTX 1000 mg×2 and 500 mg×2 was assessed by DAS28 and EULAR response. Comparative adjusted analysis was performed by analysis of variance (ANOVA).Results:Out of 468 eligible patient, 84 opted for biologic. Of which 27 patients consented for bRTX (17 female, mean age 39.5 years).13 patients opted for 1000mg×2 and 14 for 500mg×2 dose. 74% (20/27) patients were on concomitant methotrexate and 26% on hydroxychloroquine (7/27). Both doses led to significant reduction in ESR, CRP, and DAS28-ESR at 12 months (p<0.001) (Table 1).Table 1.RA outcome-measurement scores at 12 months post biosimilar Rituximab therapy.VariableBaseline12 monthsRTX 1000mg x 2(n=13)RTX 500mg x 2(n=14)RTX 1000mg x 2(n=13)RTX 500mg x 2(n=14)ESR*53.9±23.957.1±24.723.9±2.924.1±4.7CRP*6.1±3.96.9±2.92.1±0.92.3±0.9DAS28-ESR*6.1±0.36.1±0.24.0±0.44.1±0.2CD 19+ Count*# (105/L)1191.6±308.41155±289.6128.8±90.4139±90.6* p<0.0001 as compared to 12 mos vs baseline; # p<0.0001 as compared amongst groupAt the end of 12 months, compared to 1000mg, CD19 count was higher in 500mg group (p=0.25). Percentage of patients achieving EULAR moderate or no response was higher in 500mg group (37%vs29%, p=0.205), both complete and incomplete B cell depletion, but patients achieving good response was same in both groups (14.8%vs18.5%, p = 0.25). (Figure 1).Figure 1.EULAR Response at 12 monthsConclusion:Low dose bRTX is effective in DMARD refractory RA patients with similar improvements as regular dose, although CD19 depletion was less in low dose group. A larger study to establish radiographic regression with CD19 depletion and disease activity score can help in further strengthening the use of lower dose bRTX in RA leading to significant economic advantage.References:[1]Chatzidionysiou K, Lie E, Nasonov E, Lukina G,et al. Rheumatic Diseases Portuguese Register. Effectiveness of two different doses of rituximab for the treatment of rheumatoid arthritis in an international cohort: data from the CERERRA collaboration. Arthritis Res Ther. 2016 Feb 16;18:50.[2]Vital EM, Rawstron AC, Dass S, Henshaw K, Madden J, Emery P, McGonagle D. Reduced-dose rituximab in rheumatoid arthritis: efficacy depends on degree of B cell depletion. Arthritis Rheum. 2011 Mar;63(3):603-8.Disclosure of Interests:None declared

B Cell Depletion Therapy Normalizes Circulating Follicular Th Cells in Primary Sjögren Syndrome

2016 ◽  
Vol 44 (1) ◽  
pp. 49-58 ◽  
Author(s):  
Gwenny M. Verstappen ◽  
Frans G.M. Kroese ◽  
Petra M. Meiners ◽  
Odilia B. Corneth ◽  
Minke G. Huitema ◽  
...  
Keyword(s):  
T Cell ◽  
Disease Activity ◽  
B Cell ◽  
Th17 Cells ◽  
Serum Levels ◽  
Cd4 T Cell ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Tfh Cells ◽  
Primary Sjögren Syndrome

Objective.To assess the effect of B cell depletion therapy on effector CD4+ T cell homeostasis and its relation to objective measures of disease activity in patients with primary Sjögren syndrome (pSS).Methods.Twenty-four patients with pSS treated with rituximab (RTX) and 24 healthy controls (HC) were included. Frequencies of circulating effector CD4+ T cell subsets were examined by flow cytometry at baseline and 16, 24, 36, and 48 weeks after the first RTX infusion. Th1, Th2, follicular Th (TFH), and Th17 cells were discerned based on surface marker expression patterns. Additionally, intracellular cytokine staining was performed for interferon-γ, interleukin (IL)-4, IL-21, and IL-17 and serum levels of these cytokines were analyzed.Results.In patients with pSS, frequencies of circulating TFH cells and Th17 cells were increased at baseline compared with HC, whereas frequencies of Th1 and Th2 cells were unchanged. B cell depletion therapy resulted in a pronounced decrease in circulating TFH cells, whereas Th17 cells were only slightly lowered. Frequencies of IL-21–producing and IL-17–producing CD4+ T cells and serum levels of IL-21 and IL-17 were also reduced. Importantly, the decrease in circulating TFH cells was associated with lower systemic disease activity over time, as measured by the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index scores and serum IgG levels.Conclusion.B cell depletion therapy in patients with pSS results in normalization of the elevated levels of circulating TFH cells. This reduction is associated with improved objective clinical disease activity measures. Our observations illustrate the pivotal role of the crosstalk between B cells and TFH cells in the pathogenesis of pSS.

scholarly journals Induction of long-term B-cell depletion in refractory rheumatoid arthritis patients preferentially affects autoreactive more than protective humoral immunity

2012 ◽  
Vol 14 (2) ◽  
pp. R57 ◽  
Author(s):  
YK Onno Teng ◽  
Gillian Wheater ◽  
Vanessa E Hogan ◽  
Philip Stocks ◽  
EW Nivine Levarht ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Humoral Immunity ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Refractory Rheumatoid Arthritis

scholarly journals IFN signature determines responder status on B cell depletion in rheumatoid arthritis patients

2010 ◽  
Vol 69 (Suppl 2) ◽  
pp. A12-A12
Author(s):  
S Vosslamber ◽  
H G Raterman ◽  
M Schreurs ◽  
T van der Pouw Kraan ◽  
M T Nurmohamed ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cell ◽  
Cell Depletion ◽  
B Cell Depletion

Malignant B Cells Skew the Balance between Treg Cell and TH17 Cell Differentiation in B-Cell Non-Hodgkin Lymphoma (NHL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1347-1347
Author(s):  
Zhi-Zhang Yang ◽  
Anne J. Novak ◽  
Thomas E. Witzig ◽  
Stephen M. Ansell
Keyword(s):  
T Cells ◽  
Cell Differentiation ◽  
B Cells ◽  
B Cell ◽  
Cd4 T Cells ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Foxp3 Expression ◽  
Treg Cells ◽  
Th17 Cell Differentiation

Abstract Numerous clinical therapies have attempted to modulate tumor cell immunity, but for the most part, have proven unsuccessful. The inability to produce or augment an effective immune response is due in part to regulatory T (Treg) cells, which inhibit CD4 and CD8 T cell function. Our group has recently shown that Treg cell numbers are elevated in NHL tumors and that NHL B cells induce the development of Treg cells thereby inhibiting anti-tumor responses. The ability of NHL B cells to direct the cellular composition of their microenvironment is critical to our understanding of tumor immunity and we therefore wanted to determine if NHL B cells also directed the expansion or reduction of other T cell populations. IL-17-secreting CD4+ T cells (TH17), a newly characterized CD4+ T helper cell lineage, promote inflammation and play an important role in autoimmune disease. IL-17 has been shown to inhibit tumor cell growth suggesting a potential role for TH17 cells in anti-tumor immunity. We therefore set out to determine if TH17 cells were present in NHL tumors and whether or not their numbers were regulated by NHL B cells. Using unsorted mononuclear cells from malignant lymph nodes, we were unable to detect IL-17 expression in resting CD4+ T cells or CD4+ T cells activated with PMA/Ionomycin stimulation (less than 1%). However, IL-17-secreting CD4+ T cells could be detected in significant numbers in inflammatory tonsil and normal PBMCs. Interestingly, depletion of CD19+ NHL B cells from mononuclear cells obtained from patient biopsies resulted in detection of a clear population of IL-17-secreting CD4+ T cells (5%). These results suggest that NHL B cells suppress TH17 cell differentiation. The frequency of IL-17-secreting CD4+ T cells could not be further enhanced by the addition of exogenous TGF-b and IL-6, a cytokine combination favoring for TH17 differentiation, suggesting a further impairment of TH17 cell differentiation in the tumor microenvironment. In contrast, Foxp3 expression could be detected in resting CD4+ T cells (30%) and could be induced in CD4+CD25−Foxp3− T cells activated with TCR stimulation (28%). Contrary to the inhibition of TGF-b-mediated TH17 differentiation, Foxp3 expression could be dramatically upregulated by TGF-b in intratumoral CD4+ T cells (35%). In addition, lymphoma B cells strongly enhanced Foxp3 expression in intratumoral CD4+CD25−Foxp3−. Furthermore, when added together, the frequency of Foxp3+ T cells and Foxp3-inducible cells reached up to 60% of CD4+ T cells in tumor microenvironment of B-cell NHL. These findings suggest that the balance of effector TH17 cells and inhibitory Treg cells is disrupted in B-cell NHL and significantly favors the development of inhibitory Treg cells. Our data indicate that lymphoma B cells are key factor in regulating differentiation of intratumoral CD4+ T cells toward inhibitory CD4+ T cells.

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