Репозиторий Университета

© 2018 Ima-Press Publishing House. All right reserved. Objective: to analyze the levels of CD3+, CD3+CD4+, CD3+CD8+, and CD3-CD56+ T lymphocytes, FoxP3+ regulatory T cells (Treg), and CD19+ B lymphocytes in patients with early and advanced rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 45 patients previously untreated with methotrexate (MTX-naive) who had early RA and 15 patients who had advanced RA. Immunofluorescence staining and multicolor flow cytome-try assays were used to estimate the percentage and absolute (abs) counts of CD3+, CD3+CD4+, CD3+CD8+, CD3-CD16+CD56+, CD19+, Treg (FoxP3+CD25+; surface CD152+; intracellular CD152+; FoxP3+CD127; CD25+CD127-; FoxP3+ICOS+; FoxP3+CD154+; and FoxP3+CD274+. Results and discussion. The patients with early RA were found to have a lower percentage of FoxP3+CD25+ cells and lower percentages and abs counts of FoxP3+ ICOS+ cells, FoxP3+CD154+ cells, and FoxP3+ CD274+ T cells than healthy donors (p0.05 in all cases). The patients with advanced RA were also recorded to have a lower percentage of FoxP3+CD25+ cells and lower percentages and abs contents of FoxP3+ ICOS+ cells, FoxP3+CD154+ cells, and FoxP3+ CD274+ T cells (p0.05 in all cases). The patients with advanced RA compared to those with early RA had a higher content of CD4+ lymphocytes (50.7 [44.4; 53.1] and 45.0 [38.0; 49.2]) and lower percentages of CD25+CD127- T lymphocytes (5.0 [4.0; 5.7] and 6.5 [5.1; 7.9] respectively; p0.05 in all cases). Conclusion. Patients with RA (with the early or advanced stage of the disease) show a decrease in both the counts and functional activity of Treg. The patients with advanced RA compared with those with early RA showed an increase in CD4+ lymphocyte counts and a decrease in CD25+CD127- cell levels, which suggests that there are more pronounced impairments in Treg homeostasis in advanced RA.

© 2018 Ima-Press Publishing House. All rights reserved. Objective: to assess whether adalimumab (AD) can be gradually discontinued during continuous methotrexate (MTX) use in patients with early rheumatoid arthritis (ERA). Subjects and methods. Within the REMARCA (the Russian study of methotrexate and biological agents in early active arthritis) study, the investigators examined 20 patients (17 women and 3 men; median age, 51 [41.5; 56] years) with ERA (disease duration, 10 [5.5; 20] months; DAS28, 5.17 [4.37; 6.51]; 85% of the patients were seropositive for rheumatoid factor and 85% for anti-cyclic citrullinated peptide antibodies. Results and discussion. All the patients received subcutaneous MTX 25 mg/week. Twelve weeks after beginning therapy with MTX, due to its inefficiency, ADA was added according to the standard scheme. At week 24, the median DAS28 was 3.0 [1.65; 3.73]; 85% of the patients achieved remission or low disease activity. After 3 months of ADA therapy, high or moderate disease activity remained in 3 (15%) patients; median DAS28 was 4.4 [4.3; 6.1]; the drug was discontinued in them due to ineffective therapy. After 12-month follow-up, low DAS28 scores were observed in 5 (29.4%), DAS28 remission was in 12 (70.6%) of the 17 patients who continued ADA treatment; after 24 months, all the 17 patients were noted to have remission. After achieving sustained remission (≥ 6-month duration during ADA therapy), there was a carefully controlled reduction (titration) in the dose of ADA with its complete discontinuation, by maintaining remission at 36-month follow-up; the median DAS28 was 1.6 [1.4; 2.2]. During ADA treatment, one female patient developed pustular psoriasis and therefore the drug was discontinued at 24-month follow-up during the period of sustained remission. Other serious adverse events and tuberculosis cases were not recorded. Conclusion. Thus, the results of the study are indicative of the high clinical efficiency of the therapy. After ADA discontinuation, sustained remission can be maintained in patients with ERA and if they took biological agents early.

© 2018 Media Sphera Publishing Group. All rights reserved. Objective. To clarify the association between HLA-DRB1 and TNFα (-308G>A) genes polymorphism and joint destruction/further progression during 12 months of the follow-up period (FUP) in patients with early (<6 months), active, predominantly antibodies to cyclic citrullinated peptide (ACCP) and rheumatoid factor (RF)-positive rheumatoid arthritis (RA) treated according to "Treat to target" strategy. Materials and Methods. The study included 85 patients with early RA and duration of symptoms <6 months. All patients were initially assigned to subcutaneous methotrexate (MTX) with rapid dose escalation to 20-25 mg/week. Combination MTX + biological therapy, mainly adalimumab, was used when MTX was ineffective. Joint destruction was assessed by Sharp-Van der Heijde modification scoring method at baseline and after 12 months FUP. Real time polymerase chain reaction (PCR-RT) was used for TNFα gene polymorphism (-308G>A) genotyping. Low resolution PCR-RT with subsequent sequence-based typing of ∗04 were performed to study HLA-DRB1 gene polymorphism. The HLA-DRB1∗01, ∗04:01, ∗04:04, ∗04:05, ∗04:08, ∗10 alleles were categorized as SE+ (Shared Epitope) alleles. Results. As for TNFα gene polymorphism, it was demonstrated that the number of narrowings and total Sharp score values were almost twice as high at baseline in GG genotype carriers as compared to GA genotype carriers (ρ<0,005, and ρ<0,004 respectively). Similar association was found after 12mo FUP. The progression of joint destruction, assessed as the change (Δ) in the number of erosions, joint space narrowings and the total score, was statistically significantly associated with HLA-DRB1∗(SE) genotypes: The carriers of SE (SE+/SE+) double-dose had more advanced progression as compared to (SE+/SE-)/(SE-/SE-) carriers (ρ<0,028, ρ<0,019, ρ<0,035 respectively). Conclusion. Our data suggest that HLA-DRB1 (SE+) gene and TNFα (-308G>A) polymorphisms are associated with the progression of radiographic joint destruction in early, active RA patients managed according to "Treat to target" stratagy.