Background: Expression levels of cytokine and growth factor receptors have been found to be important in the regulation of their action. Tumor necrosis factor-α (TNFα) is actively involved in inflammation processes in atopic dermatitis (AD), but the role of TNFα membrane receptors (TNFR) and their regulatory function in AD remains unclear. Aim: We aimed to determine the associations of parameters of TNFRα expression on immunocompetent cells with disease severity before and after therapy in AD patients. Methods: TNFRα expression on T cells, B cells, and monocytes was evaluated by flow cytometry. To determine receptor numbers on the cells, Quantibrite PE beads were used. The content of soluble mediators was evaluated by ELISA. To reveal linear relationships between the index scoring AD (SCORAD) and the studied parameters, multiple linear regression model building was used. Results: TNFR1 and TNFR2 expression in lymphocyte and monocyte populations of AD patients was higher than in healthy individuals (HI). At the same time an increased percentage of positive cells was not associated with high receptor density, and vice versa. Serum content of TNFα, both soluble receptors, the number of TNFR2/T cells, and the percentage of TNFR2+ monocytes were found to be strongly associated with the SCORAD index. Conclusion: AD patients had increased TNFR expression on immune cells. Changes in the parameters of TNFRα expression compared to HI were associated with the disease severity index SCORAD.
Objectives: Our study aimed to define chemokine receptor profile of peripheral OCPs in rheumatoid arthritis (RA), with comparison to psoriatic arthritis (PSA), as well as their susceptibility to chemotactic signals. Methods: 129 RA, 53 PSA and 110 control patients were enrolled after Ethical approval. PB samples and synovial fluid (SF) samples, with clinical data of disease activity, inflammation and autoantibody levels were collected. Patients starting anti-TNF therapy were followed up 6 months. TNF-α and CTX serum levels were measured by ELISA. Frequency of OCP-rich subpopulation (CD3-CD19-CD56-CD11b+CD14+), expression of OC differentiation (CD115, RANK) and chemokine (CCR1, CCR2, CCR4, CXCR4) receptors was assessed by flow cytometry. OCPs were sorted using FACS, cultured with M-CSF and RANKL, stained for TRAP enzyme and mature OCs counted. Levels of CCL2, CCL3, CCL4, CCL5, CXCL9 and CXCL10 were measured using cytometric bead array, and of CXCL12 by ELISA. Osteoclastogenic effects of CCL2, CCL5 and CXCL10 were analyzed in cell culture, and chemotactic effects on OCPs were studied by cell migration assay using Transwell, with count of number of migrated cells and subsequently differentiated mature osteoclasts. Results: OCP population was moderately enlarged in PB, further expanded in SF and correlated with TNF-α and rheumatoid factor (RF) levels in patients with RA. However, sorted OCPs generated similar number of mature OCs as control. RANK+ subpopulation was enlarged in SF vs PB and correlated with number of tender joints. In PSA, the OCP population was not enlarged, but had a higher RANK expression. OCPs in RA and PSA had higher expression of CCR1, CCR2, CCR4, CXCR4, and all except CCR4 showed positive PB-to-SF gradient. RA had higher levels of CCL2, CCL3, CCL4, CCL5, CXCL9 and CXCL10, with a positive PB-to-SF gradient for all except CCL5 and CXCL9. OCP frequency correlated with levels of CCL2 and CCL5. Subset expressing CXCR4 was associated with TNF-α, CTX and RF levels and was lower in patients treated with DMARD, who at the same time had lower osteoresorption (CTX). Subset expressing CCR4 showed significant negative trend during anti-TNF treatment. CCL2, CCL5 and CXCL10 showed significant osteoclastogenic effect. CCL5 showed greatest chemotactic effect, attracting the highest number of cells in the migration assay. At the same time, attracted cells possessed greater osteoclastogenic potential. Conclusions: Our study provides evidence of the specific importance of certain chemokine signals for stimulation of OCP mobilization, subsequent tissue homing, and maturation, explaining local as well as generalized bone loss seen in RA. Novel insights in regards to migratory behavior and functional properties of PB OCPs in response to chemotactic signals could open way to new therapeutic targets in RA.
Introduction: Surgical correction of adolescent idiopathic scoliosis is inevitably accompanied by blood loss. About 37–85% of patients undergo allogeneic transfusions associated with a risk of serious complications. Prediction of the expected blood loss volume remains a topical problem. In this regard, there is a need to clarify predictors of increased blood loss. Aim: To assess the effect of vertebrectomy on the intraoperative blood loss volume during surgical correction of adolescent idiopathic scoliosis. Materials and methods: A retrospective study included 511 adolescents who underwent posterior correction of spinal deformity. Two groups were allocated: Group I consisted of 303 patients who underwent multilevel transpedicular fixation; Group II included 208 patients who underwent multilevel transpedicular fixation combined with Smith-Peterson osteotomy. Results: Intergroup comparisons revealed significant differences in the number of transpedicular fixation levels and the volume of blood loss, which were higher in Group II. After aligning the groups by the number of transpedicular fixation levels using the Propensity Score Matching method, no statistically significant difference was observed. We derived formulas for calculating the expected blood loss volume in Groups I and II. Comparison of the formulas revealed that the formula for Group II predicted a significantly lower volume of blood loss, by 2.51%, while the formula for Group I predicted a significantly higher volume of blood loss, by 3.27%. In our opinion, application of the formula that overestimates expected intraoperative blood loss is most reasonable due to a possibility of the worst case scenario during surgery; therefore, the formula for Group I approaches a universal model for use. Conclusion: Smith-Peterson osteotomy did not affect the amount of blood loss during surgical correction of adolescent idiopathic scoliosis, considering the number of transpedicular fixation levels.
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