Dynamics of lymphocyte subpopulations, CD4+CD25+CD127- T regulatory cells in patients with rheumatoid arthritis during therapy with the rituximab biosimilar Acellbia

Objective: to evaluate the effect of the rituximab (RTM) biosimilar Acellbia on the peripheral blood levels of CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD19+, and CD4+CD25+CD127- lymphocytes in patients with rheumatoid arthritis (RA).Patients and methods. Examinations were made in 20 RA patients who received 2 RTM infusions at a total dose of 1200 mg. The levels of C-reactive protein, IgM rheumatoid factor, IgG, IgM, and IgA were measured by a nephelometric method. The relative and absolute contents of CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD19+, CD4+CD25+CD127- T regulatory cells (Tregs) were estimated by multicolor flow cytofluorometry.Results and discussion. At week 24 of RTM therapy, there was a good/satisfactory effect according to EULAR criteria in 17 (85%) patients; DAS28 remission in 4 (20%), and SDAI remission in 2 (10%). The use of RTM was accompanied by a significant increase in the relative content of CD4+CD25+CD127- T lymphocytes, the median of which at weeks 12 and 24 after therapy initiation increased from 6.8 [5.2; 7.6]% to 7.3 [6.1; 8.3] and 6.97 [6.4; 8.2]%, respectively (p<0.05). The absolute peripheral blood count of Tregs tended to increase at weeks 12 after the first infusion of the drug (up to 0.05 [0.04; 0.075] ⋅ 109 /l; p=0.05). At week 24 follow-up, the patients who achieved SDAI remission/low disease activity had significantly higher baseline relative Tregs levels (7.35 [6.8; 7.97]% than those with the moderate activity of the pathological process (5.8 [4.3; 7.22] %; p<0.05).Conclusion. The use of the RTM biosimilar is accompanied by the development of complete depletion of CD19+ lymphocytes and by an increase in CD3+ and CD3+CD4+ lymphocytes and Tregs. The larger baseline number of CD4+CD25+CD127- lymphocytes is associated with the higher efficiency of RTM therapy.

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Frequencies of CD4+ T Regulatory Cells and their CD25high and FoxP3high Subsets Augment in Peripheral Blood of Patients with Acute and Chronic Brucellosis

Osong Public Health and Research Perspectives ◽

10.1016/j.phrp.2014.04.008 ◽

2014 ◽

Vol 5 (3) ◽

pp. 161-168 ◽

Cited By ~ 1

Author(s):

Abbas Bahador ◽

Jamshid Hadjati ◽

Niloofar Hassannejad ◽

Hadi Ghazanfari ◽

Mohammadreza Maracy ◽

...

Keyword(s):

Peripheral Blood ◽

T Regulatory Cells ◽

Regulatory Cells

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Effect of Interferon Alfa-2a on Peripheral Blood CD4+CD25+ T Regulatory Cells in Patients with Behcet Uveitis: Preliminary Study

International Journal of Ophthalmology and Clinical Research ◽

10.23937/2378-346x/1410012 ◽

2015 ◽

Vol 2 (1) ◽

Cited By ~ 2

Author(s):

Aylin Koc

Keyword(s):

Peripheral Blood ◽

T Regulatory Cells ◽

Interferon Alfa ◽

Regulatory Cells ◽

Preliminary Study

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Association between peripheral blood levels of C-reactive protein and Autism Spectrum Disorder in children: A systematic review and meta-analysis

Brain Behavior and Immunity ◽

10.1016/j.bbi.2020.04.008 ◽

2020 ◽

Vol 88 ◽

pp. 432-441

Author(s):

Fangna Yin ◽

Hongbing Wang ◽

Zeya Liu ◽

Junwei Gao

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorder ◽

Peripheral Blood ◽

Meta Analysis ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Blood Levels ◽

C Reactive Protein ◽

Reactive Protein

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Expression of CD62P and CD154 in peripheral blood of patients with rheumatoid arthritis and their correlation with clinical indexes

European Journal of Inflammation ◽

10.1177/2058739218822682 ◽

2019 ◽

Vol 17 ◽

pp. 205873921882268

Author(s):

Shiping Qu ◽

Chunyi Yu ◽

Qian Xing ◽

Haisheng Hu ◽

Haiyan Jin

Keyword(s):

Rheumatoid Arthritis ◽

Peripheral Blood ◽

Healthy Subjects ◽

Disease Activity Score ◽

Control Group ◽

Disease Course ◽

C Reactive Protein ◽

Reactive Protein ◽

Erythrocyte Sedimentation ◽

Pearson Test

The aim of this study is to investigate the expression of CD62P and CD154 in peripheral blood of patients with rheumatoid arthritis (RA) and their correlation with the clinical indexes of RA. A total of 60 RA patients diagnosed and treated in the Department of Rheumatism in our hospital from January to December 2016 were selected as the RA group, and 60 cases of healthy subjects were selected as the control group. CD62P and CD154 levels in peripheral blood were determined by flow cytometry using the FACS Vantage flow cytometer, and the correlation analysis with the clinical indexes of RA patients were conducted. The levels of CD62P and CD154 in the peripheral blood of RA group were 28.75% ± 1.48% and 26.84% ± 1.03%, respectively, which were significantly higher than those of the control group ( P < 0.05). The levels of white blood cell (WBC), platelet (PLT), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), and interleukin (IL)-37 in the RA group were significantly higher than those in the control group ( P < 0.05). Pearson test showed that CD62P and CD154 levels in the peripheral blood in the RA group were positively correlated with serum WBC, PLT, ESR, RF, CRP, IL-37, and disease activity score 28 (DAS28) ( P < 0.05), but not correlated with disease course ( P > 0.05). The expression of CD62P and CD154 in peripheral blood of patients with RA was upregulated, and their expression levels were correlated with the activity of RA and the degree of joint lesion.

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T regulatory cells and Th1/Th2 cytokines in peripheral blood from tuberculosis patients

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/s10096-010-0908-0 ◽

2010 ◽

Vol 29 (6) ◽

pp. 643-650 ◽

Cited By ~ 51

Author(s):

X.-Y. He ◽

L. Xiao ◽

H.-B. Chen ◽

J. Hao ◽

J. Li ◽

...

Keyword(s):

Peripheral Blood ◽

T Regulatory Cells ◽

Th2 Cytokines ◽

Regulatory Cells ◽

Tuberculosis Patients

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Regulatory T Cells in Human Autoimmune Thyroid Disease

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-2337 ◽

2006 ◽

Vol 91 (9) ◽

pp. 3639-3646 ◽

Cited By ~ 119

Author(s):

Mónica Marazuela ◽

María A. García-López ◽

Nicté Figueroa-Vega ◽

Hortensia de la Fuente ◽

Brenda Alvarado-Sánchez ◽

...

Keyword(s):

Peripheral Blood ◽

T Regulatory Cells ◽

Mononuclear Cells ◽

Thyroid Tissue ◽

T Cell Subsets ◽

Thyroid Cell ◽

Regulatory Cells ◽

Rnase Protection ◽

Autoimmune Thyroid

Abstract Context: T regulatory cells have a key role in the pathogenesis of autoimmune diseases in different animal models. However, less information is available regarding these cells in human autoimmune thyroid diseases (AITD). Objective: The objective of the study was to analyze different regulatory T cell subsets in patients with AITD. Design: We studied by flow cytometry and immunohistochemistry different T regulatory cell subsets in peripheral blood mononuclear cells (PBMCs) and thyroid cell infiltrates from 20 patients with AITD. In addition, the function of TREG lymphocytes was assessed by cell proliferation assays. Finally, TGF-β mRNA in thyroid tissue and its in vitro synthesis by thyroid mononuclear cells (TMCs) was determined by RNase protection assay and quantitative PCR. Results: PBMCs from AITD patients showed an increased percent of CD4+ lymphocytes expressing glucocorticoid-induced TNF receptor (GITR), Foxp3, IL-10, TGF-β, and CD69 as well as CD69+CD25bright, CD69+TGF-β, and CD69+IL-10+ cells, compared with controls. TMCs from these patients showed an increased proportion of CD4+GITR+, CD4+CD69+, and CD69+ cells expressing CD25bright, GITR, and Foxp3, compared with autologous PBMCs. Furthermore, a prominent infiltration of thyroid tissue by CD69+, CD25+, and GITR+ cells, with moderate levels of Foxp3+ lymphocytes, was observed. The suppressive function of peripheral blood TREG cells was defective in AITD patients. Finally, increased levels of TGF-β mRNA were found in thyroid tissue, and thyroid cell infiltrates synthesized in vitro significant levels of TGF-β upon stimulation through CD69. Conclusions: Although T regulatory cells are abundant in inflamed thyroid tissue, they are apparently unable, in most cases, to downmodulate the autoimmune response and the tissue damage seen in AITD.

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Multiple Myeloma Patients Treated with Allogeneic Stem Cell Transplantation Show an Increased Frequency of Bone Marrow-Residing CD4+Foxp3+ T Regulatory Cells.

Blood ◽

10.1182/blood.v108.11.5206.5206 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5206-5206

Author(s):

Djordje Atanackovic ◽

Yanran Cao ◽

Christiane Faltz ◽

Katrin Bartels ◽

Christine Wolschke ◽

...

Keyword(s):

Bone Marrow ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Peripheral Blood ◽

T Regulatory Cells ◽

Healthy Controls ◽

Newly Diagnosed ◽

Regulatory Cells

Abstract BACKGROUND: Immunosuppressive CD4+Foxp3+ T regulatory cells (Treg) play a vital role in immune regulation. Thus, Treg contribute to the prevention of autoimmune disease and graft-versus-host reactions following allogeneic stem cell transplantation (alloSCT) but also to the inhibition of effective anti-tumor T cell responses. It has previously been suggested that the frequency of Treg is increased in the peripheral blood of patients with multiple myeloma (MM). However, little is known about the presence of Treg in the bone marrow and it is unclear whether allogeneic stem cell transplantation might deplete Treg from this immune compartment. METHODS: In the present study, we analyzed percentages of CD4+Foxp3+ Treg as well as Treg expression of CD45RA and CCR7 in the bone marrow (BM) and in the peripheral blood of MM patients who had received alloSCT (N=42), in newly diagnosed MM patients (N=18), and in healthy controls (N=15) using flow cytometry. In addition, we performed inhibition assays in order to test the functional relevance of peripheral and BM-residing Treg. RESULTS: While newly diagnosed MM patients and healthy controls showed no significant difference in the proportions of CD4+Foxp3+ Treg in the bone marrow, percentages of BM-residing CD4+Foxp3+ T regulatory cells were markedly higher (p<0.001 and p<0.01) in patients post alloSCT (3.3±0.3%) than in normal BM (1.0±0.3%) or in BM of untreated MM patients (1.8±0.4%). In both groups of patients (p<0.05) as well as in the healthy controls (p<0.001) percentages of Treg were higher in the peripheral blood than in the bone marrow. While there were no differences regarding the percentages of peripheral Treg between the remaining groups, patients post alloSCT had higher percentages of peripheral Treg than newly diagnosed patients (5.6±0.8 vs. 3.2±0.7%, p<0.05). More than 90% of these donor-derived peripheral and BM-residing Treg expressed a memory T cell phenotype, being negative for CD45RA and CCR7. Importantly, peripheral as well as BM-residing Treg of patients post alloSCT were capable of inhibiting the proliferation of autologous non-Treg CD4+ T cells. CONCLUSION: Our study demonstrates for the first time an increased frequency of immunosuppressive Treg in the bone marrow of MM patients. Remarkably, in our patients these memory-type Treg were all donor-derived and led to an efficient replenishment of Treg in the periphery. These Treg might be necessary for the prevention of graft-versus-host disease in the transplanted MM patients, however, they might also contribute to the failure of an effective graft-versus-myeloma effect in the majority of the patients.

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