To detect receptor activator of nuclear factor kappa B ligand (RANKL) expressed on B10 cells in rheumatoid arthritis (RA) and to evaluate the correlation between RANKL-producing B10 cells in RA and clinical features and laboratory parameters, trying to reveal the possible role of B10 cells in the pathogenesis of RA and the potential mechanism of impaired immunosuppressive capacities.25 RA patients and 20 healthy volunteers were enrolled. These RA patients did not received treatment with glucocorticoids, disease-modifying anti-rheumatic drug and biologics during the recent half of a year. The levels of RANKL-producing B10 cells were measured by flow cytometry (FCM) and polymerase chain reaction (PCR). The correlation between the frequencies of RANKL-producing B10 cells in RA and clinical data, laboratory parameters were analyzed. The role of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) in inducing RANKL expression in B10 cells was evaluated by in vitro stimulation assay. Independent samples t test, Pearson and Spearman correlation were used for statistical analysis.B10 cells were capable of producing RANKL at a low level in health controls. The frequencies of RANKL-producing B10 cells were markedly higher in RA patients than in health controls (3.65%±1.59% vs. 2.25%±0.68%, P<0.01). The frequencies of these cells correlated positively with RA tender joint counts, swollen joint counts and disease activity score in 28 joints (DAS28) (r=0.479, P=0.035; r=0.519, P=0.008; r=0.526, P=0.019). However, no correlation was found between these cells and RA patient age, disease duration, or the levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF) and anti-citrullinated peptide antibody (ACPA). After in vitro stimulation by TNF-α, but not IL-1β, B10 cells isolated from healthy donors demonstrated fundamentally upregulated expression of RANKL.Our studies showed the frequencies of RANKL-producing B10 cells were markedly higher in RA patients, and their frequencies were positively correlated with RA tender joint counts, swollen joint counts and DAS28. These findings suggested that B10 cells might be involved in RA bone destruction.
The NKT-like cells were known to play a role of the suppression in many chronic inflammatory diseases. This study was designed to investigate both of the expression and the possible role of NKT-like cells in SLE patients.
Methods
79 patients with SLE together with 30 age- and sex-matched healthy controls were enrolled. Flow cytometric determination of peripheral NKT-like cells was carried out for all participants by detecting the absolute counts (Abs) and percentage (%) of CD3+CD16+CD56+ cells. Disease activity index, laboratory parameters and clinical manifestations were collected. The correlation between the cells and these parameters were analyzed.
Results
SLE patients had, with respect to controls, considerably decreased values of NKT-like cells (P < 0.001 in both absolute number and percentage). The absolute number of NKT-like cells were found to have positive correlations with WBC, RBC, PLT, C3, C4, IgM and negative correlations with the disease duration, SLEDAI-2K, anti-dsDNA, anti-nucleosome, anti-ribosomal protein, and CRP, ESR. Meanwhile, it was found that the percentage values of NKT-like cells decreased in SLE patients with nephritis which was correlated with anti-ribosomal protein and CRP in comparison to SLE patients without nephritis. Moreover, an increase in the NKT-like cell counts was also observed in the patients with a clinical response to the treatment.
Conclusions
The absolute counts and frequencies of NKT-like cells decreased in SLE patients significantly, which correlated to disease activities and could recover to normal after the treatment. The NKT-like cells may play an important role in the pathogenesis of SLE and could be a useful marker in the disease assessment.
Hyperactivated B cells have been demonstrated the contribution to the development of rheumatoid arthritis (RA). While the recognition of the negative regulatory function of B cells further promoted our understanding of their pathogenic role in RA. Recently, a new population of granzyme B (GrB)-producing B cells was identified, which was proved to be involved in cancer and infectious diseases. However, their characteristics and roles in RA remain to be elucidated. In the present study, we aim to further characterize whether B cells could produce GrB and reveal their potential role in the pathogenesis of RA. Here, we further demonstrated peripheral blood B cells from healthy individuals could produce and secrete GrB, which could be enhanced by IL-21 and/or anti-B-cell receptor stimulation. These cells could negatively regulate Th1 and Th17 cells partly via downregulating TCR zeta chain and inducing T cell apoptosis, which might be termed as GrB-producing regulatory B cells (Bregs). These GrB-producing Bregs were significantly decreased under RA circumstance concomitant of lower levels of IL-21 receptor, with impaired regulatory functions on Th1 and Th17 cells. Moreover, the frequencies of these cells were negatively correlated with RA patient disease activity and clinical features. After effective therapy with disease remission in RA, these GrB-producing Bregs could be recovered. Therefore, our data revealed that B cells could produce GrB with immunosuppressive functions, and the impairment of this Breg subset was correlated with RA pathogenesis.
Raman spectra integrated multiple potential biomarkers into one spectroscopic signature for the diagnosis of RA. In the recognition of ACPA-negative RA, the sensitivity and specificity also reached 95.6% and 92.8%, respectively.
Objectives . IL-33, a newly found cytokine which is involved in joint inflammation, could be blocked by a decoy receptor—sST2. The expression and correlation of IL-33 and sST2 in rheumatoid arthritis (RA) are of great interest. Methods . Synovial fluid (SF) was obtained from 120 RA and 30 osteoarthritis (OA) patients, and paired sera were collected from 54 of these RA patients. The levels of IL-33 and sST2 were measured by ELISA. Results . SF IL-33 was significantly higher in RA than in OA, which was correlated with disease activity score 28, erythrocyte sedimentation rate, rheumatoid factor (RF)-IgM, RF-IgG, glucose phosphate isomerase (GPI), and immunoglobulin. Serum IL-33 was correlated positively with SF IL-33 in RA. Furthermore, it was correlated with RF-IgM and GPI. sST2 was partly detectable in RA (13 out of 54, 24.1%), while not in OA. Serum sST2 in RA had no significant correlation with serum IL-33 or SF IL-33. However, SFs from both RA and OA patients did not express sST2. Conclusions . This study supported that IL-33 played an important role in the local pathogenesis of RA. Considering the tight correlation between IL-33 and clinical features, it may become a new target of local treatment.
To investigate the effect of myeloid-derived suppressor cells (MDSC) on pro-liferation of B lymphocytes in rheumatoid arthritis (RA) patients.The peripheral blood specimens were collected from 15 healthy adults and 38 RA patients who were divided into high disease activity group, medium activity group and low activity group according to their 28-joint disease activity score (DAS28). And the frequencies of MDSC were determined by flow cytometry. Then, B cells and MDSC were isolated by flow cytometry, respectively. B cells were labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE) and then were co-cultured with MDSC in the presence of 3 mg/L anti-CD40 antibody and 10 mg/L CpG, for 3 days. Flow cytometry was performed to investigate the proliferation of B cells.MDSC expanded markedly in high disease activity patients (7.13% ±2.17%) compared with medium (5.35%±1.36%) and low disease activity patients (4.72%±1.08%) or healthy controls (4.79%±1.02%) (P<0.05), and there were no statistical differences between healthy controls, medium and low disease activity RA (P>0.05). Moreover, the frequencies of MDSC were positively correlated with the DAS28 (P<0.05). After co-culture, MDSC significantly promoted B cell proliferation (P<0.01).Our studies showed that MDSC expanded obviously in high disease activity RA patients, and their frequencies were positively correlated with the disease activities. Furthermore, MDSC could promote autologous B cell proliferation remarkably in vitro. These findings suggest that MDSC might be involved in RA pathogenesis through regulating B cell functions.
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