Clinical and experimental rheumatology最新文献

Objectives: Human T follicular helper (Tfh) cells are classified into three subsets: Tfh1, Tfh2, and Tfh17 cells. Among them,Tfh2 cells are defined as CXCR3-negative and CCR6-negative, and may contain diverse cell populations. We examined whether CCR4 serves as a marker for identifying Tfh2 cells that produce interleukin (IL)-4 and its involvement in IgG4-related disease (IgG4-RD).

Methods: Single cell analysis of IL-4-producing Tfh subset was performed using multi-colour flow cytometry and t-SNE method. Blood samples were obtained from 23 treatment-naïve patients with active IgG4-RD. CCR4+Tfh2 cells were also assessed in affected tissues of IgG4-RD by flow cytometry and immunohistochemical staining.

Results: Tfh2 cells expressing CCR4 were identified as Tfh cells that specifically produce IL-4. CCR4+Tfh2 cells showed higher expression of GATA-3 and ICOS than CCR4-Tfh2 cells, while there was no difference in the expression of BCL-6 and FOXP3. The proportion of CCR4+Tfh2 cells in peripheral blood was increased in IgG4-RD compared to healthy controls, and even more CCR4+Tfh2 cells infiltrated into the affected lesions. CCR4+GATA-3+Tfh2 cells diffusely infiltrated tertiary lymphoid tissues and storiform fibrosis lesions. The proportion of CCR4+Tfh2 cells showed a significant correlation specifically with serum IgG4 levels among clinical indicators. Glucocorticoid therapy did not correct the increased proportion of CCR4+Tfh2 cells.

Conclusions: CCR4 serves as a marker for identifying Tfh2 cells that specifically produce IL-4. CCR4+Tfh2 cells are a widely present T cell population that infiltrates tertiary lymphoid tissues and storiform fibrosis of IgG4-RD. Glucocorticoid fails to effectively target CCR4+Tfh2 cells that may contribute to a high relapse rate during glucocorticoid tapering in this disease.

Objectives: To develop evidenced recommendations to allow the global systemic lupus erythematosus (SLE) advocacy community to effectively advocate for change and improve care for patients with SLE.

Methods: A Global Working Group consisting of representatives from patient advocacy groups, professional organisations, and the SLE healthcare community defined key areas of unmet need in patients with SLE. Targeted principles for each area of unmet need guided a literature review to investigate the current global situation, pre-existing advocacy efforts, and best practices from other therapy areas. The results from this literature review allowed the Working Group to develop recommendations to improve care for patients with SLE.

Results: Barriers faced by patients with SLE can stem from poor recognition of symptoms, which leads to delays in accurate diagnosis, cycling between different healthcare professionals, and inconsistencies in receiving optimal care. Patient access to approved treatments for SLE also remains limited. This Patient Charter, co-developed with a group of internationally recognised clinicians and patient advocates, sets out the minimum standard of care people living with SLE should expect and receive under 4 principles with distinct recommendations for change.

Conclusions: The intention is to improve health outcomes by uniting and empowering patients, caregivers, patient groups, and healthcare professionals to advocate for reforms to healthcare practices for people living with SLE.

Objectives: Distinction of dermal thickening at fingers is paramount in recognition of systemic sclerosis (SSc). Evaluation of skin thickening by modified Rodnan skin score (mRSS) might be challenging. Simple and practical tools are needed to help distinguishing (non-) thickened skin in daily practice. High frequency ultrasonography (HFUS) can reliably measure dermal thickness (DT). In this pilot study we search for a DT cut-off value (as a simple HFUS discriminator) to distinguish between healthy control (HC) and SSc skin at the left index finger (F2L).

Methods: DT evaluated by HFUS (18MHz probe) in SSc patients (2013 ACR/EULAR criteria) was compared with HC in a cross-sectional study. A cut-off value was selected by receiver operating characteristic (ROC) curve analysis.

Results: 63 consecutive SSc patients (mean age 52±14 SD, 78% female) and 48 HC (mean age 36±14 SD, 62% female) underwent HFUS. Mean DT at F2L was 1.44 mm (± 0.39 SD) in SSc patients and 1.06 mm (± 0.19 SD) in HC. Based on ROC-curve analysis, a DT cut-off of 1.5 mm is proposed as simple HFUS discriminator between HC and SSc, at a specificity of 1 and a sensitivity of 0.32. The final model had an area under the curve of 0.83 (95%CI 0.75-0.90).

Conclusions: A simple HFUS discriminator between skin thickness of HC versus SSc, i.e., DT as measured at F2L, at a cut-off of 1.5 mm, is proposed for daily use in rheumatology clinics. Further validation should be executed through prospective multicentric cohorts.

Objectives: Patients with fibromyalgia syndrome (FM) often suffer from sleep disorders, adversely affecting their prognosis. Active non-pharmacological therapies are considered the mainstay of treatment for FM, but the optimal treatment choice remains contentious. We aimed to compare and rank community-based non-pharmacological interventions for FM with sleep disorder by quantifying information from randomised controlled trials (RCTs).

Methods: Two authors independently selected studies and extracted data. We searched Embase, MEDLINE, PubMed, CNKI, Scopus, Google Scholar, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) from the database inception to June 2022. Network meta-analyses were conducted using a frequency-based method. The study protocol is registered with the Prospective Register of Systematic Reviews (PROSPERO, CRD 42022373704). Eleven RCTs (n=729) were included in the analysis.

Results: Mindfulness-based therapy (MBT) (SMD=-0.84 (95% CI: -1.49 to -0.20)) and cognitive behavioural therapy (CBT) (SMD=-0.54 (95% CI: -1.04 to -0.04)) were associated with significantly improved sleep symptoms in a patient with FM compared with usual care.

Conclusions: MBT exhibited the highest probability (91.14%) of being the most effective intervention in sleep improvement, followed by CBT (72.39%). MBT exhibited marked advantages over other interventions and is likely to have optimal efficacy in ameliorating sleep disorders.

Objectives: To investigate the correlation between innate lymphoid cell (ILC) subsets with T-helper (Th) cells and to explore the effect of ILCs on T cells in rheumatoid arthritis (RA).

Methods: We analysed the frequencies of ILC subsets in RA patients with varying disease activity and their correlation with Th cell subsets. We further investigated this correlation in various organs of collagen-induced arthritis (CIA) mice. The effects of ILCs on CD4+ T cells were determined by in vitro cell co-culture experiments.

Results: ILCs were less frequent in RA patients than in healthy controls, with higher levels of group 3 ILCs (ILC3s) in RA (p<0.05). ILC3s correlated positively with Th1 and Th17 cells in RA peripheral blood (p<0.05). In the peripheral blood, spleen, and lymph nodes of CIA, ILC3s decreased and then increased during arthritis progression. ILC3s correlated positively with Th1 and Th17 cells in the spleen and lymph nodes of CIA (p<0.05). NKp46+ ILC3s in the spleen positively correlated with Th1 and Th17 cells (p<0.05). Under Th17 cell differentiation conditions, co-culturing CIA-derived ILC3s directly with naive CD4+ T cells promoted Th17 differentiation and increased IL-17 secretion. However, co-culturing through a transwell insert impeded Th17 differentiation without affecting IL-17 secretion.

Conclusions: ILC3s positively correlated with Th1 and Th17 cells in RA. In CIA, the frequencies of ILC3s changed with disease development and showed a positive correlation with Th1 and Th17 cells. ILC3s may facilitate the differentiation of Th17 cells through direct cell-cell contact.

Gout is a self-limited inflammatory disease caused by the deposition of monosodium urate (MSU) crystals in joints and surrounding tissues due to abnormal purine metabolism. Neutrophil extracellular traps (NETs) are formed by neutrophils in response to pathogen attack. During gout, NETs induced by MSU crystals exacerbate inflammation, and aggregated NETs (aggNETs) promote the resolution of gout-associated inflammation by encapsulating MSU crystals, degrading cytokines and chemokines, and blocking the recruitment and activation of neutrophils. With disease progression, NETs participate in the formation of tophi. Therefore, aggNETs are a possible mechanism of spontaneous gout regression. Studying the specific mechanism by which NETs affect inflammatory bursts and spontaneous regression in gout patients is important. This review summarises the role of NETs in different stages of gout and the specific pathogenesis of NETs in gout to provide new ideas for the diagnosis and treatment of gout.

Objectives: To evaluate prevalence of ultrasonographic remission (USR) and concordance with clinical remission in "drug-free" or "on-treatment" patients with early rheumatoid arthritis (RA).

Methods: We carried out a cross-sectional study including consecutive early RA patients in SDAI remission ≥6 months in the period 06/2022 to 02/2023. CDAI, DAS28, DAS44 and Boolean remission were also evaluated. Patients underwent B-mode and Power Doppler (PD) assessments of 42 joints and 20 tendons. Synovitis, tenosynovitis and PD were graded semi-quantitatively (0-3) using standardised scores. Four definitions of USR were examined: USR1: absence of synovial hypertrophy (SH) and PD; USR2: SH≤1 and PD=0; USR3: SH≤1 and PD≤1; USR4: PD negative.

Results: Eighty patients were enrolled, of whom 12 drug-free. Overall remission rates were 100.0%, 83.7%, 91.2%, 96.2% and 80.0% for SDAI, CDIA, DAS28, DAS44 and ACR/EULAR Boolean criteria, respectively. 100% of drug-free patients were in remission according to all indices. The rate of USR in drug-free versus on-treatment remission was 58.3%, 66.7%, 66.7%, 83.3% versus 70.6%, 85.3%, 88.2%, 91.2% for USR1, USR2, USR3 and USR4, respectively.

Conclusions: While clinical remission seems more frequent in drug-free patients, USR is more often observed on-treatment.