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Dermatomyositis (DM) represents a multifaceted chronic inflammatory myopathy, primarily manifesting as progressive deterioration of muscular and cutaneous tissues. Despite an incomplete comprehension of DM's etiology and pathogenesis, current evidence implicates the involvement of T lymphocyte infiltration, extensive cytokine release, myositis-specific antibodies, and myositis-associated antibodies in disease development. Serum soluble interleukin-2 receptor (sIL-2R) frequently serves as a marker for T cell activation; however, its role remains elusive. Consequently, this investigation sought to elucidate the association between sIL-2R levels, peripheral blood lymphocyte subset counts, and related cytokines in DM patients, with the aim of uncovering the intricate mechanisms underlying DM and establishing a theoretical foundation for the implementation of precise, targeted, individualized immunomodulatory therapy. In this study, a cohort of 60 dermatomyositis (DM) patients, comprising 32 with inactive DM and 28 with active DM, was enrolled and stratified into inactive and active groups based on the Myositis Disease Activity Visual Analogue Scale (MYOACT). Flow cytometry was employed to quantify the absolute counts of peripheral lymphocyte subsets and CD4+T cell subsets in each group, while a flow cytometry bead array was utilized to measure serum cytokine levels. In a comparative analysis between healthy individuals and patients diagnosed with DM, we observed a marked elevation in serum sIL-2R concentrations (P < 0.001) and T-helper 17 cell/regulatory T cell (Th17/Treg) ratios (P < 0.01) within the latter group. A positive correlation was identified between serum sIL-2R levels and various parameters, including ESR, CRP, VAS, AST, CKMB, LDH, HBDH, PT, APTT, DDi, IL-6, IL-10, and IFN-γlevels (P < 0.05). In contrast, serum sIL-2R levels demonstrated a negative correlation with LY, HGB, ALB, Th17 cell populations, and Th17/Treg cell ratios (P < 0.05). Employing multivariate logistic regression, we identified serum sIL-2R concentrations as an independent risk factor for both disease activity and hepatic involvement in DM patients. Moreover, receiver operating characteristic (ROC) curve analyses revealed that serum sIL-2R levels significantly contributed to the differentiation of disease activity and the detection of liver involvement in DM patients, with areas under the ROC curve (AUC) of 0.757 (95% CI 0.630–0.884, P = 0.001) and 0.826 (95% CI 0.717–0.935, P < 0.001), respectively. This study highlights the potential utility of serum sIL-2R levels as a valuable biomarker for assessing disease activity and liver involvement in dermatomyositis. Elevated serum concentrations of sIL-2R were observed in patients with DM, exhibiting significant associations with Th17 cell populations and Th17/ Treg ratios. These findings indicate that sIL-2R may be implicated in the immunopathogenesis of DM, thereby warranting further investigation to elucidate its role in the disease process. [ABSTRACT FROM AUTHOR]

Objective Patients with ankylosing spondylitis (AS) carry an increased burden of cardiovascular diseases (CVD), but features denoting the development of CVD in AS are unclear. This study aimed to evaluate the percentage and absolute number of lymphocytes and CD4+T cells in AS patients complicated with CVD (AS-CVD) and determine whether circulating T helper 17 (Th17) cells are associated with the development of CVD in AS. Method A total of 117 AS patients (46 had CVD and 71 had no CVD) were enrolled in this retrospective study. The percentage and absolute number of lymphocytes and CD4+T cells were determined by flow cytometry. Associations between CVD and clinical markers were analysed using logistic regression. Results The ratio of Th17/Treg cells (0.30 vs 0.19, P   =  0.014) and the absolute number of Th17 cells (7.27 cells/μL vs 4.34 cells/μL, P   <  0.001) was significantly elevated in AS-CVD group compared with AS-no-CVD group. Multivariate logistic regression revealed that elevated Th17 cells (OR = 1.20, P   =  0.016) were associated with CVD complications in AS. Receiver operating characteristic (ROC) curves showed a contribution of Th17 cell for distinguishing AS patients with CVD, with the areas under the ROC curve (AUCs) of 0.729 (95% CI: 0.632, 0.825, P   <  0.001). Conclusion Our findings provide evidence for the association between Th17 cells and increased cardiovascular risk in AS. Th17 cells may contribute to accelerated atherogenesis and increased cardiovascular burden in AS and be valuable for early assessment and management of AS-CVD. [ABSTRACT FROM AUTHOR]

Objective: To identify lymphocyte and CD4 + T cell subset characteristics, particularly regulatory T cells (Tregs), in active rheumatoid arthritis (RA) patients with coronary artery disease (CAD). Methods: A total of 54 RA patients with CAD (RA-CAD group), 43 RA patients without CAD (pure RA group), and 43 healthy controls (HC group) were enrolled. The absolute number and frequency of lymphocyte subpopulations and CD4 + T cell subsets were analyzed by flow cytometry. Serum levels of cytokines were analyzed using a cytometric bead array. Clinical and laboratory data were collected retrospectively and their correlation with CD4 + T subsets were analyzed. Results: There was a significant decrease in the absolute number of Treg cells (CD4 + CD25 + Foxp3 + T cells) in the RA-CAD group compared to the pure RA group (p < 0.001). Similarly, both the absolute number (p = 0.001) and frequency (p = 0.011) of Tregs in the RA-CAD group were decreased compared to the HCs, causing a Th17/Treg imbalance (p = 0.044). No difference was found in the absolute number and frequency of Treg cells between the pure RA and HC groups. However, the absolute Th17 cell count was increased in the pure RA group (p = 0.032). The serum level of cytokine IL-17 was lower in the RA-CAD group than in the pure RA group (p = 0.023). In the RA-CAD group, the Treg number was negatively correlated with the RA disease activity score and ESR value, and LDL and ApoB100 levels were negatively correlated with the number of Th17 cells. Conclusions: Active RA patients with CAD sustain more severe immune tolerance damage and Th17/Treg disorder. Monitoring of lymphocyte and CD4 + T cell subsets, particularly Treg cells, is crucial to understanding immune status in this group. Focusing on RA activity and CAD risk control, immune-regulatory therapy based on the Treg level may be more beneficial for RA patients with CAD. [ABSTRACT FROM AUTHOR]

• The double negative T cells in patients with AAV were amplified. • More CD62L-CD45RO- double negative T cells in patients with AAV. • Double negative T cells produced IFN-γ, IL-4 and IL-17 in patients with AAV. • Expanded double negative T cells in patients with AAV and renal vasculitis. • Conventional methylprednisolone effectively reduced double negative T cells. CD3+CD4−CD8− [double-negative (DN)] T cells play vital roles in the pathogenesis of autoimmune disorders. In this study, we investigated the exact level of DN T cells in patients with antineutrophil cytoplasmic autoantibody (ANCA)–associated vasculitis (AAV). Forty patients with active AAV and 19 healthy controls (HCs) were enrolled in this study. Peripheral mononuclear cells were characterised phenotypically via flow cytometry. The potential clinical value of DN T cells was then assessed by the receiver operating characteristic (ROC) curves. The percentage (p < 0.001) and absolute number (p = 0.028) of DN T cells were found to be significantly higher in patients with AAV than in HCs. Relative to HCs, a lower percentage of DN T cells from patients with AAV was of the CD62L+CD45RO+ phenotype (p = 0.024), a higher percentage of these cells was of the CD62L–CD45RO– phenotype (p = 0.043). Patients with AAV had increased percentages of DN T cells expressing interferon (IFN)-γ (p = 0.032), interleukin (IL)-4 (p = 0.039) and IL-17 (p = 0.042). Furthermore, the percentages of IL-17–producing CD4+ T cells and IFN-γ–producing CD8+ T cells were significantly higher in patients with AAV than in HCs (p = 0.014, p = 0.008). Compared with the CD4+ and CD8+ T-cell subsets, DN T cells had the highest fractions of intracellular IL-17 in HCs and patients with AAV (both p < 0.001). In patients with AAV and renal damage, the percentage of DN T cells was expanded relative to that in patients without renal damage (p = 0.016). In addition, conventional methylprednisolone effectively reduced the percentage and overall number of DN T cells in patients with AAV (p = 0.028, p = 0.007). DN T cells represent a T-lymphocyte subset that produces inflammatory cytokines (IFN-γ, IL-4 and IL-17) and is absolutely elevated in patients with AAV. Additional investigations are required to determine their precise role in patients with AAV. [ABSTRACT FROM AUTHOR]

Background: We have reported previously the insufficient absolute number or functional defects of regulatory T cells (Tregs) in patients with rheumatoid arthritis (RA), challenging conventional unspecific immunosuppressive therapy. Sirolimus, a mTOR inhibitor, is reported to allow growth of functional Tregs; here, we investigated the efficacy of low-dose sirolimus combined with conventional immunosuppressants (sirolimus immunoregulation therapy) for RA treatment with lower side effects and better tolerance.Methods: In this nonblinded and parallel-group trial, we randomly assigned 62 patients to receive conventional glucocorticoids and immunosuppressants with or without sirolimus at a dosage of 0.5 mg on alternate days for 24 weeks in a 2 : 1 ratio. The demographic features, clinical manifestations, and laboratory indicators including peripheral blood lymphocyte subgroups and CD4+T subsets were compared before and after the treatment.Results: Finally, 37 patients in the sirolimus group and 18 in the conventional treated group completed the 6-month study. By 24 weeks, the patients with sirolimus experienced significant reduction in disease activity indicators including DAS28, ESR, and the number of tender joints and swollen joints (p < 0.001). Notably, they had a higher level of Tregs as compared with those with conventional therapy alone (p < 0.05), indicating that sirolimus could partly restore the reduced Tregs. Concomitantly, their usage of immunosuppressants for controlling disease activity was decreased as compared with the conventional group with no difference in blood routine, and liver and renal functions both before and after the treatment of sirolimus and between the two groups (p > 0.05).Conclusions: Low-dose sirolimus immunoregulatory therapy selectively upregulated Tregs and partly replaced the usage of immunosuppressants to control disease activity without overtreatment and evaluable side effect. Further study is required using a large sample of RA patients treated with sirolimus for a longer period. This trial is registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/showproj.aspx?proj=17245). [ABSTRACT FROM AUTHOR]

Objective: Accumulating evidence indicates that regulatory T cells (Tregs) may be involved in the pathogenesis of ankylosing spondylitis (AS). As different markers have been used to identify Tregs, some studies on the proportions of Tregs in AS patients have generated considerable controversy. To clarify the status of Tregs in such patients, we determine the proportion changes of peripheral Tregs during development of the disease, with different cellular markers.Methods: We systematically searched Embase, PubMed, Cochrane, Web of Knowledge, FDA.gov, and Clinical Trials.gov for the studies reporting the proportion of Tregs in AS patients. Using the PRISMA guidelines, we performed a random-effects meta-analysis of the frequencies of peripheral Tregs defined in different ways. Inconsistency was evaluated using the I-squared index (I2), and publication bias was assessed by examining funnel plot asymmetry using the Begger and Egger tests.Results: A total 29 studies involving 1732 participants were included in the meta-analysis. Their conclusions of using the diversity of Tregs surface markers were inconsistent with each other. No significant difference in the proportions of Tregs was evident regardless of the definitions used [-0.709, (-1.455, 0.037, p = 0.063), I2 = 97.3%]. Six studies used "single CD25-positive" cells as Tregs, which revealed a significant increase in AS patients compared with healthy blood donors [0.736, (0.138, 1.334), p = 0.016, I2 = 80.7%]. Notably, the proportions of "CD4+CD25+FOXP3+," "CD4+CD25highCD127low/-," or "CD4+CD25+CD127low" T cells were lower in AS patients [-2.856, (-4.645, -1.066), p = 0.002; -1.812, (-2.648, -0.977), p < 0.001; -1.12, (-1.605, -0.635), p < 0.001]. Tregs defined as "CD25high," "CD25bright," "CD25bright/highCD127low/-," "CD4+FOXP3+," "CD4+CD25highFOXP3+," and "CD4+CD25+CD127-" did not differ in proportion between AS patients and healthy blood donors.Conclusions: The levels of Tregs varied based on the cellular identification markers used. The proportions of CD4+CD25+FOXP3+Tregs, CD4+CD25highCD127low/-, or CD4+CD25+CD127low in blood of AS patients were significantly decreased as compared with those in healthy blood donors, and our findings lend support to the idea that the Treg status of AS patients is important. And we recommend the above as the best definition of Tregs when evaluating the status of such patients. [ABSTRACT FROM AUTHOR]

Objective. To conduct a meta-analysis, assessing the efficacy and safety of the combination treatment of dexamethasone and rituximab for adults with ITP (primary immune thrombocytopenia). Methods. Randomized controlled trials that compared rituximab and dexamethasone combination treatment to dexamethasone monotherapy in the treatment of adults with ITP were collected by searching Pubmed, Embase, Cochrane, China National Knowledge (CNKI), Wanfang database, and Sino Med. We conducted pooled analyses on OR (overall response) rate, CR (complete response) rate, PR (partial response) rate, SR (sustained response) rate, R (relapse) rate, change in Treg cell count (mean [SD]), and AE (adverse event). GRADE pro scale was used to assess the quality of the evidence. Publication bias was assessed with Egger's test method. Results. A total of 11 randomized controlled trials were eligible for inclusion. The overall efficacy estimates favored combination arm in terms of OR rate at month 3, CR rate at week 4 and month 3, SR rate, and Treg cell count at week 2. Subgroup analysis showed that females obtained a higher OR rate than males did at week 4. No significant difference was found in pooled analysis of relapse rate between combination arm and monotherapy arm. The comparison of serious AE and other AEs showed no significant difference either. A total of 19 outcomes were assessed by GRADE pro software, of which 79% (15/19) was scaled as moderate-to-high level. Publication bias existed in studies on OR at week 4 (P=0.025), CR at week 4 (P=0.017), infection (P=0.006), and rash (P=0.028) of the AEs. Conclusion. Dexamethasone combined with rituximab can provide a better long-term response in the treatment of adults with ITP and will not increase the risk of adverse effects. [ABSTRACT FROM AUTHOR]

Dermatomyositis (DM) is closely associated with infection, the levels of peripheral lymphocyte subpopulations are rarely studied in patients with DM combined with Epstein-Barr virus (EBV)/cytomegalovirus (CMV) infection. Here, we aimed to observe the level of lymphocyte subsets, especially Th17, regulatory T (Treg) cells in DM combined with EBV/CMV viremia, and explore the effects of short-term low-dose IL-2. 34 DM patients combined with EBV/CMV viremia (DM infection group), 31 DM patients without infection (DM non-infection group) and 20 healthy controls were entrolled in our study. In DM infection group, 13 patients received low-dose IL-2 at 0.50 Million IU/day for a five-day course on the basis of conventional treatment. All subjects had completed the decetion of the absolute numbers of lymphocytes subsets in peripheral blood by flow cytometry. The infection group had significant decreases levels of total T, total B, NK, CD4 + T cells and CD4 + T subsets (Th1, Th2, Th17, Treg cells). Compare to the healthy controls, Th17 cells was significantly reduced in the infection group, but not in the non-infection group (P < 0.001 vs. P = 0.171). After low-dose IL-2 therapy, the levels of Treg (P = 0.001) cells and Th17 cells were significantly elevated, re-balancing the Th17 and Treg proportions. The absolute numbers of Th17 and Treg cells in DM patients with EBV/CMV viremia is further reduced. In addition to Treg cells, a decrease in Th17 cells may be also a crucial feature. Low-dose IL-2 treatment may be beneficial and safe prospect immunomodulatory therapy to restores imbalance between Th17 and Treg cells for these patients. Low-dose IL-2 therapy may be a new prospect field with some challenges such as long-term immunoregulatory utility in various virus infection. [ABSTRACT FROM AUTHOR]

The breakdown of immune tolerance mediated by the reduced regulatory T (Treg) cell contributes to autoimmune diseases, which can be recovered by the short-term and low-dose interleukin 2 (IL-2). However, the role of Treg cells in microscopic polyangiitis (MPA) and the efficacy of short-term and low-dose IL-2 for MPA remain unclear. Therefore, we performed a retrospective study to explore the role of Treg cells and evaluate the efficacy of short-term and low-dose IL-2 therapy in MPA. 52 MPA were collected as research objects, and 15 of them voluntarily received short-term and low-dose IL-2 subcutaneous injection combined with conventional therapy. 60 volunteers were recruited as health controls (HC) according to the inclusion and exclusion criteria. The number of circulating CD4 + T cell subsets was detected by flow cytometry. Patients with MPA had reduced circulating Treg cells than HCs (P < 0.001), and the level of Treg cells were reduced in MPA-activity and ANCA-positive group (P = 0.018 and P = 0.008 respectively). The patients with lower Treg cells had the higher incidence of the organ involvement (P = 0.006). The level of Treg cells in MPA was doubled after the short-term and low-dose IL-2 combined with conventional therapy (P = 0.001), and the disease activity indicators such as ESR and CRP were improved (P < 0.05) with no apparent side effects. Patients with MPA had reduced circulating Treg cells, especially the MPA-activity and ANCA-positive patients. And the patients with lower Treg cells were more likely to exhibit the organ involvement. Short-term and low-dose IL-2 therapy increased the reduced Treg cells and promoted the remission of the disease at a certain extent with well tolerance. [ABSTRACT FROM AUTHOR]

Patients with rheumatoid arthritis (RA) are more susceptible to infections, which elevate the levels of relative cytokines. However, the ability of the cytokines levels to predicate bacterial infections in RA patients remains unclear. Here, we assessed the ability of the combination of serum cytokine levels and blood parameters to diagnose bacterial infections in RA patients. We measured the levels of a panel of serum cytokine and blood parameters in 168 RA patients and 81 healthy individuals. RA patients were divided into the bacterial infection (INFE) group (n = 76) and RA flare without INFE group (n = 92). Bacterial infection was confirmed by microbial culture, imaging, antibiotic response, and typical clinical symptoms. The discriminative ability of the combination of the cytokine levels and inflammatory parameters was assessed using the receiver-operating characteristic (ROC) curves analysis and a novel bioscore system. The levels of interleukin (IL)-6 (p = 0.006), IL-10 (p = 0.019), interferon (IFN)-γ (p = 0.033), CRP (p < 0.001), and ESR (p < 0.001) were higher in patients of the INFE group than in patients with RA flare, and the absolute numbers of CD19+ B cells (p < 0.001) and CD4+ T cells (p = 0.009) were lower. For discriminating bacterial infection, the combination of IL-6, IL-10, IFN-γ, ESR, CRP, CD19+ B cells, and CD4+ T cells, provided an area under the curve (AUC) of 0.827 [(95% confidence interval (CI): 0.760–0.881)], which was profoundly larger than that of IL-6, IL-10, IFN-γ, ESR, CRP, CD19+ B cells, or CD4+ T cells alone. In addition, we also developed a bioscore system based on the combination of these seven biomarkers. Seventeen (100%) patients with a bioscore of 0 were non-infected, while seven (100%) patients with a score of 7 had bacterial infections. The bioscore based on the combination of ESR, CRP, IL-6, IL-10, IFN-γ, CD19+ B cells and CD4+ T cells may be a promising and robust tool to diagnose bacterial infections in RA patients. [ABSTRACT FROM AUTHOR]