Objective Inter‐alpha‐trypsin inhibitor heavy chain 4 (ITIH4) regulates immunity and inflammation, but its clinical role in rheumatoid arthritis (RA) patients remains unclear. Hence, this study was conducted to explore the association of circulating ITIH4 with disease risk, clinical features, inflammatory cytokines, and treatment outcomes of RA. Methods After the enrollment of 93 active RA patients and 50 health controls (HCs), their serum ITIH4 level was analyzed by enzyme‐linked immunosorbent assay (ELISA). For RA patients only, serum ITIH4 level at week (W) 6 and W12 after treatment was also analyzed. Besides, serum tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐1β, IL‐6, and IL‐17A at baseline of RA patients were also detected by ELISA. Results ITIH4 was downregulated in RA patients (151.1 (interquartile range (IQR): 106.2–213.5) ng/mL) than in HCs (306.8 (IQR: 238.9–435.1) ng/mL) (p < 0.001). Furthermore, ITIH4 was negatively related to C‐reactive protein (CRP) (rs = −0.358, p < 0.001) and 28‐joint disease activity score using erythrocyte sedimentation rate (DAS28‐ESR) (rs = −0.253, p = 0.014) in RA patients, but not correlated with other clinical features (all p > 0.05). Besides, ITIH4 was negatively linked with TNF‐α (rs = −0.337, p = 0.001), IL‐6 (rs = −0.221, p = 0.033), and IL‐17A (rs = −0.368, p < 0.001) in RA patients, but not correlated with IL‐1β (rs = −0.195, p = 0.061). Moreover, ITIH4 was gradually elevated in RA patients from baseline to W12 after treatment (p < 0.001). Additionally, the increment of ITIH4 at W6 and W12 was linked with treatment response and remission in RA patients (all p < 0.05). Conclusion Circulating ITIH4 possesses clinical utility in monitoring disease risk, inflammation, disease activity, and treatment outcomes of RA.

Dehydroevodiamine (DHE) is an effective natural active substance extracted from Euodiae Fructus , which is a widely used herbal drug in traditional Chinese medicine. The focus of this study was to test the possibility of using DHE in the treatment of rheumatoid arthritis (RA) diseases. A rat model of adjuvant-induced arthritis (AIA) was generated using Complete Freund’s Adjuvant (CFA). Body weight changes, arthritis scores, ankle pathology, tumor necrosis factor-alpha (TNF-α), interleukin-1β(IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) secretion, as well as matrix metalloproteinase (MMP) expression in joint tissue, were measured as indicators of viability of DHE medicated AIA rats. Human fibroblast-like synoviocytes (MH7A cells) were connected to check these impacts. The results confirmed that DHE administration had an excellent therapeutic impact on the AIA rat model, substantially relieving joint swelling, inhibiting synovial pannus hyperplasia, and decreasing joint scores. In addition, the serum enzyme-linked immunosorbent assay (ELISA) showed that DHE treatment reduced the expression of pro-inflammatory factors in AIA rats. The immunohistochemical results showed that DHE treatment could reduce the synthesis of MMPs such as matrix metalloproteinase-1(MMP-1) and matrix metalloproteinase-3 (MMP-3) in the ankle tissue of AIA rats. In vitro, DHE inhibited cell proliferation, mRNA transcription, protein synthesis of proinflammatory factors such as IL-1βand IL-6, and matrix metalloproteinases such as MMP-1 and MMP-3. Furthermore, DHE inhibited the phosphorylation levels of p38, JNK, and ERK proteins in TNF-α-treated MH7A cells.This work assessed the effect of DHE in AIA rats and revealed its mechanism in vitro.

An immunosensor was developed on an interdigitated electrode (IDE) by voltammetry sensing for the early identification of the autoimmune disease ‘rheumatoid arthritis (RA)’ by detecting the biomarker anti-cyclic citrullinated peptide antibody (anti-CCP). Higher immobilization of cyclic citrullinated peptide (CCP) as a probe was achieved by using green synthesized iron oxide nanoparticles (IONPs). Field-emission scanning electron microscopy and field-emission transmission electron microscopy observations revealed that the polydispersed material displayed multifaceted features. X-ray photoelectron spectroscopy analysis confirms the occurrence of Fe, O, and C groups on the synthesized IONPs. IONPs were immobilized with a probe on IDE through bifunctional aldehyde-amine linkers. Due to the elevated occupancy of CCP and the highly efficient electric transfer from IONPs, higher changes in current are observed upon binding of anti-CCP with CCP. In the linear range from 8 to 250 pg/mL, the sensitivity and detection limit of anti-CCP were 8 and 15 pg/mL, respectively, with a regression coefficient of y = 1E−06x−3E−07; R2 = 0.9637. Control experiments with nonimmune antibody and anti-carcinoembryonic antigen indicate the specific detection of anti-CCP. Furthermore, spiking of anti-CCP in human serum does not interfere, representing the specific detection of anti-CCP. This CCP-immobilized IDE through IONP helps to quantify anti-CCP levels in the biological fluid for diagnosing RA.

No abstract