П р о г р е с с в р е в м а т о л о г и и в Х Х I в е к е Е.Н. Александровазаведующая лабораторией иммунологии и молекулярной биологии ревматических заболеваний ФГБНУ НИИР им. В.А. Насоновой, докт. мед. наук А.С. Авдееванаучный сотрудник лаборатории иммунологии и молекулярной биологии ревматических заболеваний ФГБНУ НИИР им. В.А. Насоновой, канд. мед. наук Е.Л. Насоновдиректор ФГБНУ «НИИР им. В.А. Насоновой», академик РАН, докт. мед. наук, профессор
Objective: to investigate the count and characteristics of the phenotype of T regulatory cells (Treg) in the peripheral blood of healthy donors and patients with early rheumatoid arthritis (RA), by using multicolor flow cytometry.Subjects and methods. The investigation enrolled 39 patients with early RA. The percentage and absolute count of Treg (FoxP3+CD25+, surface CD152+, intracellular CD152+, FoxP3+CD127, CD25+CD127, FoxP3+ICOS+, FoxP3+CD154+; and FoxP3+CD274+) was determined by multicolor flow-cytometry. A control group consisted of 20 healthy donors matched for sex and age with the examined patients.Results and discussion. In the patients included in the study, the median [25th; 75th percentiles] DAS28 was 5.01 [4.2; 5.8]; high, moderate, and low activity showed 22 (48.9%), 20 (44.4%), and 3 (6.7%) patients, respectively. The patients with early RA had a lower percentage of FoxP3+CD25+ cells and a lower percentage and absolute count of FoxP3+ICOS+, FoxP3+CD154+, and FoxP3+CD274+ T cells than the healthy donors (p<0.05 in all cases). There was a negative correlation of the percentage of FoxP3+CD25+ cells with C-reactive protein (CRP) (r = -0.4), that of intracellular CD152+ with DAS28 (r = -0.35), erythrocyte sedimentation rate (ESR) (r = -0.46), and CRP (r=-0.54); that of FoxP3+CD127 with CRP (r = -0.42); that of CD25+CD127 with DAS28 (r = -0.38), Simplified Disease Activity Index (r = -0.41), Clinical Disease Activity Index (r = -0.36), ESR (r = -0.39), and CRP (r = -0.47) (p < 0.05 in all cases).Conclusion. The findings suggest that the functional activity of Treg is impaired in early RA, which has an impact on the activity of the inflammatory process.
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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