Clinical and experimental rheumatology最新文献

Objectives: Recurrent thrombosis is one of the main clinical features of antiphospholipid syndrome (APS), and recent studies revealed that APS shares similar pathophysiological mechanisms with atherosclerosis. Oxidised low-density lipoprotein (OxLDL) and antibodies against OxLDL (anti-OxLDL) are involved in the development of atherosclerosis. This study aims to investigate the clinical significance of OxLDL and anti-OxLDL in APS patients.

Methods: One hundred and seventy APS patients and 39 healthy controls (HC) were enrolled. Clinical and laboratory data were collected from Clinical Data Center of Peking University People's Hospital. OxLDL and anti-OxLDL were detected using enzyme-linked immunosorbent assay.

Results: Among the 170 APS patients, 106 had isolated thrombotic APS. Compared with HC, APS patients exhibited higher titres of OxLDL [413.86 (220.11-853.67) ng/mL vs. 45.54 (0-105.98) ng/mL, p<0.001] and anti-OxLDL [107.62 (75.68-174.18) U/L vs. 44.13 (18.44-79.76) U/L, p<0.001]. Also, APS patients exhibited a higher positivity rate for OxLDL (88.2% vs. 5.1%, p<0.001) and anti-OxLDL (84.1% vs. 36.5%, p<0.001) compared to HC. APS patients with elevated levels of OxLDL had a higher rate of LAC positivity (68.0% vs. 45.0%, p=0.042). Furthermore, APS patients with positive anti-OxLDL demonstrated a higher occurrence of venous thrombosis (46.2% vs. 18.5%, p=0.008) and a lower rate of Coomb's test positivity (52.6% vs. 76.2%, p=0.049). Multivariate logistic regression revealed that anti-OxLDL positivity (OR 12.424, 95%CI 1.108-139.330, p=0.041) were risk factors for venous thrombotic APS.

Conclusions: This study indicates that the presence of anti-OxLDL may serve as potential markers for venous thrombosis in APS patients. OxLDL and anti-OxLDL may function as valuable biomarkers for monitoring APS.

Objectives: To perform a systematic review and meta-analysis to assess the clinical efficacy of collagen-based supplements on knee osteoarthritis (OA) symptoms.

Methods: Until October 2023, we conducted searches on the MEDLINE, EMBASE, Web of Science, and Scopus databases to identify randomised controlled trials (RCTs) that reported the effects of oral collagen-based supplements on knee OA. Quantitative data from outcomes were pooled using a random- or fixed-effects model (depending on inter-study variability) and the generic inverse variance method. The Cochrane Risk of Bias 2.0 tool was employed to assess the risk of bias.

Results: This systematic review incorporated information of 870 participants included from 11 RCTs, with 451 allocated to the collagen supplementation group and 419 to the placebo group. The meta-analysis revealed an overall significant improvement of both function [MD, -6.46 (95% CI -9.52, -3.40); I2=75%; p=0.00001] and pain scores [MD, -13.63 (95% CI -20.67, -6.58); I2=88%; p=0.00001], favouring collagen supplementation.

Conclusions: The results of this meta-analysis suggest that oral collagen administration relieves OA symptoms. Our findings revealed noteworthy improvements, statistically and clinically, in both functional and pain scores.

Left ventricular diastolic dysfunction (LVDD) plays a central role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), a major manifestation of heart failure (HF). Low-grade inflammatory reaction is the key mechanism leading to LVDD. Rheumatoid arthritis (RA) is a systemic inflammatory disease and affects 0.5-1.0% of the adult population. Several epidemiologic studies find that the risk of LVDD is increased in RA than in the general population. Since inflammation plays an important role in the pathogenesis of LVDD and RA is a disease characterised by chronic systemic inflammation. RA may be involved in the occurrence and development of LVDD. This review summarises the pathogenesis, predictors, and management of LVDD in patients with RA.

Objectives: Psoriatic arthritis (PsA) is an immune-inflammatory disease occurring in a subgroup of patients suffering from psoriasis. Dactylitis is recognised as a hallmark of PsA, being present in about 50% of patients. This article gives an overview of the complexity of psoriatic dactylitis, looking at clinical aspects as well as pathogenetic aspects and subsequent insights into treatment strategies.

Methods: The review focuses on the main evidence on pathogenesis, clinical features, and management of psoriatic dactylitis.

Results: In recent years, more studies have focused their attention on dactylitis in PsA patients, leading to a greater understanding of its pathogenesis and clinical presentation and to a growing expansion of the therapeutic armamentarium. Dactylitis is frequently associated with more severe PsA phenotype, often representing the initial feature of the disease. Its prompt recognition can be key for addressing early diagnosis and therapy of PsA, thus leading to better clinical and radiographic outcomes.

Conclusions: There has been considerable progress in understanding psoriatic dactylitis, but major challenges remain. Although there has been a recent expansion in the therapeutic armamentarium for psoriatic dactylitis, there is still a paucity of evidence on a precision approach to this manifestation.

Chronic rheumatological diseases are multifactorial conditions in which both the neuroendocrine hormone pathway, including cortisol, sex hormones and active vitamin D3 (calcitriol), all deriving from cholesterol, and the epigenetic modifications that they cause play an important role. In fact, epigenetics modulates the function of the DNA of immune cells, through three main mechanisms: DNA methylation, modifications to the histones that make up chromatin and production of non-coding RNAs (microRNA - miRNA). In this narrative review, the main data regarding the epigenetic modifications induced by cortisol, 17β-oestradiol, progesterone, testosterone and calcitriol on immune cells were collected, discussing how these can interfere in the predisposition and course of chronic rheumatological diseases (i.e. rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis). An ever-increasing number of miRNAs have been identified, which are produced by neuroendocrine hormones and can influence the inflammatory-fibrotic response at various levels. Concerning the involvements of the neuro-endocrine-immunology within the pathophysiology of rheumatic diseases, the epigenetic effects induced by steroid hormones must be taken into consideration to evaluate their impact on the progression of the single condition and even inside the single patient.

Psoriatic arthritis (PsA) predominantly emerges in individuals previously diagnosed with psoriasis (PsO), offering a unique opportunity to study the transition from PsO to PsA. This progression provides a window to identify characteristics of PsO patients who may develop PsA, facilitating early intervention and potentially informing prevention and treatment strategies. This review evaluates a wide array of research focusing on various risk factors for PsA development. These factors span demographic characteristics, concomitant diseases and habits, characteristics of skin and nail psoriatic disease, and symptoms and imaging abnormalities associated with PsA. By summarising the existing literature, this review critically examines each risk factor, highlighting the strengths and limitations inherent in the studies. Each section of the review not only summarises the current state of knowledge but also includes an expert opinion, culminating in a final concluding remark. This integration allows physicians to utilise the confluence of established literature and ongoing clinical experience, facilitating a rationalised decision-making process that is deeply informed by both empirical evidence and practical insights.

Objectives: To evaluate the role of Fcγ receptors (FcγR) and peptidyl arginine deiminase (PAD) in anti-citrullinated protein antibody (ACPA)-induced fibroblast-like synoviocytes (FLSs)-mediated osteoclastogenesis in patients with rheumatoid arthritis (RA).

Methods: FLSs and peripheral blood mononuclear cells were collected from patients with RA. We stimulated RA-FLS with ACPA (100 ng/ml) with and without anti-cluster of differentiation (CD)32a/CD64 (FcγRIIA/FcγRI) antibody and PAD-2/4 inhibitors. Flow cytometry and enzyme-linked immunosorbent assay were also performed. CD14+ monocytes were cultured with receptor activator of nuclear factor kappa beta (RANKL) and macrophage colony-stimulating factor, and ACPA-stimulated RA-FLSs were added. These cells were cultured for 14 days, and osteoclastogenesis was quantified using tartrate-resistant acid phosphatase (TRAP) staining.

Results: ACPA increased RANKL+ and tumour necrotic factor-alpha (TNF-α+) FLS, which decreased dose-dependently by adding 5 and 10 ug/mL anti-CD64 antibody rather than anti-CD32a antibody. In PAD inhibitor experiments, the proportion of RANKL+ and TNF-α+ FLS decreased in 50 μM condition containing PAD-2 inhibitor rather than PAD-4 inhibitor. The co-culture of ACPA-stimulated RA-FLSs and osteoclast precursors increased the TRAP+ multinucleated osteoclast count, which was decreased by anti-CD64 antibody and PAD2 inhibitor.

Conclusions: The present study showed that ACPA increased RANKL and pro-inflammatory cytokine expression in RA-FLSs, and ACPA-activated RA-FLSs could augment osteoclastogenesis. These processes were inhibited by treatment with anti-CD64 antibody and PAD-2 inhibitors. These results show that CD64 and PAD-2-induced pathways may be involved in ACPA-induced FLS activation and osteoclastogenesis in patients with RA. Therefore, regulating the CD64 and PAD-2 pathways may improve RA treatment.

Objectives: The challenge of achieving low disease activity or remission in psoriatic arthritis (PsA) is an unmet need for many patients. Persistent disease activity in PsA may require treatment adjustments due to its complex pathogenesis and varied tissue involvement, highlighting the need for dedicated definitions. This study evaluates patients' frequency and contributing factors with potential "difficult-to-treat PsA (D2TPsA)", similar to the EULAR definition of D2T rheumatoid arthritis.

Methods: A retrospective study was conducted at two tertiary centres to define potential D2TPsA, defined as failure of ≥1 conventional synthetic disease-modifying anti-rheumatic drug (DMARD) and ≥2 biological or targeted synthetic DMARDs with different mechanisms of action.

Results: Of the 171 patients included in the study, 116 (67.8%) were women; the average age was 48.16 ±11.23 years. D2TPsA was detected in 33 patients (19.3%). This group exhibited a longer disease duration, higher disease burden (median number of tender and swollen joints, patient and physician global evaluation, morning stiffness, erythrocyte sedimentation rate and C-reactive protein, DAPSA), HLA-B27 positivity, and higher prevalence of peripheral involvement. Secukinumab usage and mean glucocorticosteroid dosage were significantly higher in the D2TPsA group. Comorbidities such as fibromyalgia (FM) and diabetes mellitus (DM) and the median number of comorbidities were significantly higher in D2TPsA. In multivariate analysis, FM, DM, and HLA-B27 positivity were independently associated with D2TPsA.

Conclusions: This study underscores the impact of comorbidities on PsA disease activity and emphasises the need for further research to differentiate treatment challenges influenced by comorbidities from true treatment resistance.