Elevated levels of Metrnl in rheumatoid arthritis: Association with disease activity.

BACKGROUND: Meteorin-like (Metrnl) is a novel adipokine that is highly expressed in white adipose tissues. Whether Metrnl plays a role in rheumatoid arthritis (RA) remains unclear. In this study, sera from 159 RA patients, 28 osteoarthritis (OA) patients, and 50 healthy individuals were included. The serum levels of Metrnl were measured using an enzyme-linked immunosorbent assay. Clinical parameters, including disease activity score 28 (DAS28), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), antibodies to cyclic citrulline peptide (anti-CCP), inflammatory cytokines, and blood biochemical indices were collected. RESULTS: Metrnl levels were higher in RA patients compared to OA patients and controls. In the RA group, serum Metrnl levels were positively correlated with DAS28, RF, and CRP levels. However, in the RA group, serum Metrnl levels were not correlated with ESR, anti-CCP, immunoglobulins, and blood biochemical indices. CONCLUSION: This study showed that Metrnl is involved in the pathogenesis of RA. Increase in serum Metrnl levels is closely related to RA activity.

IL-34 affects fibroblast-like synoviocyte proliferation, apoptosis and function by regulating IL-17.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by proliferation and insufficient apoptosis of fibroblast-like synoviocytes (FLSs).The biology and functions of interleukin (IL)-34 are only beginning to be uncovered. We previously demonstrated IL-34 could upregulate the expression of IL-17 in RA patients. In this study, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry of Annexin V and PI staining were performed to assess cell proliferation and apoptosis progression in RA-FLSs after stimulated with increasing concentrations of IL-34, respectively. Inflammatory cytokines and angiogenic factors were measured using quantitative real-time PCR, Western blotting and ELISA. We explored the association between IL-34 and RA-FLS proliferation and apoptosis in the context of RA. Stimulating RA-FLSs with different concentrations of IL-34 significantly promoted the proliferation and inhibited the apoptosis of RA-FLSs in a concentration-dependent manner. Neutralization of IL-17 with the IL-17 inhibitor plumbagin (PB) reduced the effects of IL-34. Proinflammatory cytokine (IL-17A IL-6 and tumor necrosis factor-α, TNF-α) and angiogenic factor (vascular endothelial growth factor, VEGF and hypoxia-inducible factor-1α, HIF-1α) expression was markedly upregulated in RA-FLSs stimulated by IL-34. PB-mediated inhibition of IL-17A also decreased the expression of IL-6, TNF-α, HIF-1α and VEGF in RA-FLSs. Taken together, these findings suggest that targeting IL-34 production in RA-FLSs may be a therapeutic strategy for RA.

Effect of IL-34 on T helper 17 cell proliferation and IL-17 secretion by peripheral blood mononuclear cells from rheumatoid arthritis patients.

Interleukin (IL)-34 is a new pro-inflammatory cytokine with elevated expression in rheumatoid arthritis (RA) patients. Our previous study showed that the frequency of T helper 17 (Th17) cells was also elevated in RA patients. Our study aimed to determine the effects of IL-34 on the proliferation, transcription factor expression and cytokine secretion of different subgroups of CD4 + T cells [Th1, Th2, Th17 and regulatory T (Treg) cells] in RA patients. Peripheral blood mononuclear cells (PBMCs) were isolated from the peripheral blood of 10 RA patients and stimulated with different concentrations of recombinant human (rh) IL-34 (0, 25, 50 and 100 ng/ml). Flow cytometry was used to determine the frequencies of the 4 subgroups of CD4 + T cells. Reverse transcription-PCR, western blotting and enzyme-linked immunosorbent assays were used to determine the mRNA and protein expression levels of transcription factors and cytokines. As a result, the frequency of Th17 cells was obviously increased under IL-34 stimulation. Moreover, the expression of the transcription factor retinoic acid-related orphan receptor (ROR-γt) and secretion of IL-17 by PBMCs were increased by stimulation with IL-34. However, there were no effects of IL-34 on transcription factors or cytokine secretion in Th1, Th2 and Treg cells. In conclusion, IL-34 can improve the proliferation of Th17 cells and expression of IL-17 in RA patients.

Association Between Adiponectin and Clinical Manifestations in Rheumatoid Arthritis.

Adiponectin (APN) belongs to adipokines. Previous studies showed contradictory results that have both proinflammatory and anti-inflammatory effects in rheumatoid arthritis (RA). We set out to detect the levels of APN and the correlations between APN and the clinical manifestations in RA patients. Sera of 60 newly diagnosed patients with RA and 29 age- and gender-matched healthy subjects were collected. Clinical parameters, including C-reactive protein (CRP), erythrocyte sedimentation rate, rheumatoid factor (RF), antibodies to cyclic citrullinated peptide, disease activity score 28, and bone erosion conditions, were collected. The serum levels of total APN and high-molecular-weight APN (HMW-APN) were detected by enzyme-linked immunosorbent assay. As a result, total APN and HMW-APN levels were all lower in patients with RA compared with healthy controls. The levels of APN and HMW-APN were all positively correlated with CRP levels. There was also positive correlation between HMW-APN levels and RF levels. Moreover, patients with higher disease activities had higher HMW-APN levels; patients with more severe synovial thickening had higher APN and HMW-APN levels. Therefore, APN, especially HMW-APN, may play a regulatory role in RA.

Elevated levels of anti-carbamylated protein antibody in patients with rheumatoid arthritis: association with disease activity and bone destruction.

To measure the serum levels of anticarbamylated protein (CarP) antibodies in patients with rheumatoid arthritis (RA) in China and to evaluate the association of anti-CarP antibodies with clinical parameters and disease activity. 260 Chinese patients with RA, 40 patients with osteoarthritis (OA), 88 patients with spondyloarthritis (SpA) and 77 healthy controls were included. The serum levels of anti-CarP antibodies were detected by ELISA. Blood tests to detect the anticyclic citrullinated peptide (CCP) antibody level, rheumatoid factor (RF) level, erythrocyte sedimentation rate, C reactive protein level and Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) were performed by standard methods. Bone erosion was assessed by colour Doppler ultrasonography. A total of 18.8% of patients with RA and 9.4% of anti-CCP antibody and RF-double-negative patients were positive for anti-CarP antibody. The anti-CarP antibody level was significantly higher in patients with RA than in patients with OA or SpA and in healthy controls. Univariate and multivariate analyses showed that the level of anti-CarP antibody was positively correlated with DAS28-ESR; the higher a level of serum anti-CarP antibody, the higher the DAS28-ESR score. Anti-CarP-positive patients had higher disease activity scores than anti-CarP-negative patients. Moreover, anti-CarP-positive patients had a higher risk of developing bone erosion. The anti-CarP antibody was found to play an important role in the diagnosis of RA, especially in anti-CCP antibody and RF-double-negative patients. The anti-CarP antibody is a potential marker of disease activity and bone erosion in RA.

Serum levels of interleukin-34 and clinical correlation in patients with primary Sjögren's syndrome.

OBJECTIVES: To measure the levels of serum interleukin (IL)-34 in patients with primary Sjögren's syndrome (pSS) and evaluate the cytokine's clinical association with the disease. METHODS: Serum samples were obtained from 66 pSS patients and 32 healthy controls (HCs) and measured by enzyme-linked immunosorbent assay for IL-34 levels. The clinical parameters, including autoantibodies, immunoglobulins (Igs), complements (Cs), inflammatory indicators, involvement of the blood system, lung and arthritis, were collected simultaneously. Two-sample t test was applied for comparison between 2 groups, and Pearson's correlation coefficient was used to assess the associations between IL-34 levels and laboratory parameters. RESULTS: Serum IL-34 levels were significantly elevated in pSS patients compared with HCs. Patients with anti-Ro/SSA antibody positivity showed higher serum IL-34 levels than those who were negative, as did the anti-La/SSB antibody-positive patients. Serum IL-34 levels were positively associated with the levels of rheumatoid factor, IgG and gamma-globulin, but not associated with IgA, IgM, C3, C4, erythrocyte sedimentation rate or C-reactive protein. For the pSS subgroups with and without leucopenia, thrombocytopenia, anemia or interstitial lung disease (ILD), there was no significant difference in serum IL-34 levels. Interestingly, the pSS patients with arthritis had higher levels of IL-34 compared with the no-arthritis patients. CONCLUSIONS: IL-34 may be involved in B cell activation and production of antibodies in pSS.