Clinical and experimental rheumatology最新文献

Objectives: Treatment with tumour necrosis factor inhibitors (TNFi) has significantly improved outcomes in uveitis associated with juvenile idiopathic arthritis (JIA-U). This study examines a CARRA Registry cohort of JIA-U patients on TNFi to analyse utilisation patterns and identify factors associated with response.

Methods: This retrospective cohort study used CARRA Registry data for subjects aged 0-25 with JIA-U who had uveitis onset before the age of 19, and ever used TNFi. We collected data about demographics, uveitis courses, and treatment. We defined TNFi response and identified associated characteristics. As appropriate, comparisons between factors were tested using t-test, Chi-square, and Fisher's exact test. Multivariable logistic regression was used to model TNFi response.

Results: Among 871 JIA-U subjects, 616 (70.7%) used TNFi; 558 met inclusion criteria; 418 (74.9%) had successful treatment under TNFi. Among the 140 (25.1%) TNFi non-responders, 117 remained on TNFi and 23 discontinued. Multivariate analysis found significant TNFi success associations with White race (OR=2.08, p=0.005) and non-oligoarticular JIA (OR=1.58, p=0.044).

Conclusions: In this CARRA Registry cohort of patients with JIA-U, a large proportion used a TNFi for uveitis. The percentage successfully treated with TNFi is consistent with the current literature. White race and non-oligoarticular JIA were associated with a successful response to TNFi.

Objectives: To determine if the subtype of vascular ultrasound (US) presentation is associated with different types of ischaemic complications (IC) in giant cell arteritis (GCA).

Methods: Retrospective observational analysis of GCA clinically confirmed patients referred to US fast-track clinics at two centres. All patients underwent baseline US of cranial and extracranial arteries (carotid, subclavian and axillary). Two patterns of IC were analysed: the occurrence of acute anterior ischaemic optic neuropathy (AION) or the presence of a non-AION pattern (including stroke, acute coronary syndrome, pulmonary embolism or peripheral artery disease) at diagnosis and in the following 3 months, excluding other potentially implicated causes.

Results: Of 188 clinically confirmed GCA patients, 43 (22.9%) had IC: 24 (12.8%) AION and 19 (10.1%) non-AION. Patients with AION more often exhibited US cranial involvement versus those with non-AION IC and without IC (100%, 63.2%, and 79.3%, respectively; p=0.009). Patients with AION less frequently presented signs of US large vessel (LV)-GCA than those with non-AION IC and without IC (25%, 63.2% and 55.2%, respectively; p=0.014). Patients with previous polymyalgia rheumatica (PMR) (p=0.049) or concomitant PMR symptoms at the time of diagnosis (p=0.014) showed less frequent AION. In contrast, patients with non-AION IC more frequently had positive LV-GCA US findings vs the other two groups (63.2%, 25% and 55.2%, respectively; p=0.014).

Conclusions: The subtype of vascular US presentation influences the IC in GCA. US cranial-GCA patients more frequently present AION, while predominantly US LV-GCA more frequently exhibit non-AION IC.

Objectives: Human epididymis protein 4 (HE4) inhibits the degradation of type I collagen, thus promoting fibrosis. We aimed to investigate serum HE4 levels in patients with idiopathic inflammatory myopathies (IIMs), as potential biomarker of interstitial lung disease (ILD).

Methods: IIMs patients followed in our centre between June 2020 and January 2023 were enrolled. ILD was detected by high-resolution computed tomography (CT) and pulmonary function tests. Serum HE4 levels were measured in patients and controls. Progressive fibrosing (PF-) ILD was evaluated in patients with available 2-year follow-up (INBUILD criteria).

Resilts: We enrolled 90 consecutive IIMs patients (68% females, mean age 59.5 [52.75- 66.0] years) and 42 healthy, age- and sexmatched controls. ILD was diagnosed in 44 (49%) patients. Serum HE4 levels were higher in IIMs patients than controls: 78.55 [54.6-114.4] vs. 51.05 [41.8-62.8] pmol/L (p=0.001). IIMs-ILD patients had higher levels of HE4 vs. those without ILD (193.7 [78.92-137.42] vs. 58.15 [48.32-79] pmol/L, p<0.0001). Serum HE4 levels correlated inversely with diffusing capacity for carbon monoxide (rho=-0.556, p<0.0001) and total lung capacity (rho=-0.459, p=0.001). Serum HE4 levels were the only variable independently associated with IIMs-ILD in two models of multivariate analysis: OR 1.063 (CI 95% 1.02-1.108), p=0.004, and OR 1.059 (CI 95% 1.020-1.099), p=0.003. PF-ILD was detected in 39.4% of IIMs-ILD patients with available follow-up (33/44), without any significant association with baseline serum HE4 levels.

Conclusions: HE4 might be a useful biomarker in the identification and assessment of ILD in IIMs patients.

Objectives: To investigate the clinical characteristics of pharyngeal and laryngeal lesions in patients with anti-melanoma differentiation-associated gene 5 antibodies-positive dermatomyositis (anti-MDA5-positive DM).

Methods: Serological indicators of 131 anti-MDA5-positive DM patients were analysed. All 35 patients with pharyngeal and laryngeal symptoms underwent electronic laryngoscopy examinations.

Results: Pharyngeal and laryngeal symptoms were observed in 26.7% of anti-MDA5-positive DM patients. Low levels of haemoglobin, albumin, prealbumin, high-density lipoprotein and rapidly progressive interstitial lung disease mainly appeared in patients with pharyngeal and laryngeal involvement compared to those without involvement. However, no significant difference in mortality was found between the two groups. The number of patients with pharyngeal and laryngeal involvement was significantly higher in anti-Ro-52 antibody-positive patients than in anti-Ro-52 antibody-negative patients. Patients with higher serum ferritin levels (1000 ng/ml ≤ serum ferritin ≤ 1500 ng/ml) were more likely to develop pharyngeal and laryngeal involvement compared to those with lower serum ferritin levels (serum ferritin < 500 ng/ml). Electronic laryngoscopy examinations effectively assisted rheumatologists in assessing the conditions of the pharyngeal mucosa, arytenoid area, epiglottis, and vocal cords. Some patients also presented with rare lesions such as pharyngeal posterior wall fistulas, epiglottic ulcers, and vocal cord white lesions.

Conclusions: 1. Pharyngeal and laryngeal lesions are not uncommon in anti-MDA5-positive DM, these patients have poorer nutritional status and more severe lung lesions; 2. Positive anti-Ro-52 antibodies and high serum ferritin levels are closely associated with pharyngeal and laryngeal involvement in anti-MDA5-positive DM; 3. Electronic laryngoscopy plays a crucial role in the diagnosis and evaluation of pharyngeal and laryngeal conditions.

This review discusses the clinical utility of salivary gland ultrasonography (SGUS) and lacrimal gland ultrasonography (LGUS) in primary Sjögren's syndrome (SjS). Several studies have shown that SGUS findings improve the diagnostic performance of the recent SjS classification criteria. Lacrimal gland ultrasonography findings can also aid in the diagnosis of SjS. However, SGUS and LGUS findings correlated with salivary or lacrimal gland function and minor salivary gland biopsy findings. A better treatment response to rituximab and salivary stimulants was observed in SjS patients with lower SGUS scores. In addition, the clinical implications of Doppler ultrasonography and ultrasound elastography of the salivary and lacrimal glands were investigated in patients with SjS.This review highlights the advantages of SGUS and LGUS in the diagnosis and prediction of salivary and lacrimal gland functions and treatment response in patients with SjS. Additionally, modalities other than B-mode ultrasonography, such as Doppler ultrasonography and ultrasound elastography, have been actively studied to demonstrate the clinical utility of SjS. Ultrasonography has great advantages such as immediate performance and interpretation, no harmful complications, and no discomfort to patients. Therefore, SGUS and LGUS are potentially useful diagnostic and predictive tools for SjS.

The pathogenesis of Sjögren's disease (SjD) is still elusive; however, the disease is widely recognised as a multistep disorder triggered by the interplay of environmental, hormonal and genetic factors. Innate immune system plays a crucial role in the initiation of the inflammatory process, but the amplification and the perpetuation of the autoimmune process require a continual interaction between the innate and adaptive immune systems. Several important contributions elucidating SjD pathogenesis have been recently published due to emerging technologies. This review provides an overview of the recent literature focusing, in the first part, on new insights into genetic and epigenetics studies. In the second part, we will discuss new findings related to salivary epithelial glandular cells and their interaction with other immune cells, type I interferon signature and innate immunity. Finally, as ectopic germinal centres like structures in the salivary glands of patients with SjD have been critically involved in autoreactive B cell activation and have been associated with progression towards B cell lymphomas, we will focus on new insights into their regulation in SjD and novel insights into the transition to lymphoma. Hopefully, a better comprehension of SjD complexity will pave the way to highly targeted therapeutic strategies.

Objectives: Primary Sjögren's syndrome (pSS) is an inflammatory systemic autoimmune disease, while the role and mechanisms of pyroptosis in pSS remain largely undefined.

Methods: Pyroptosis-related genes and gene expression data were obtained from the Molecular Signatures Database and NCBI GEO databases. Differentially expressed genes (DEGs) and pyroptosis-related hub genes were identified by R software. Functional enrichment analyses were conducted using the "ClusterProfiler" R package and WebGestalt7. CIBERSORTx was used to calculate the correlations between immune cells and pyroptosis. Subsequently, histological staining was performed on salivary gland samples from non-pSS and pSS patients to identify the expression of pyroptosis-related genes. Immunofluorescence double staining was conducted to validate the correlation between immune cells and pyroptosis.

Results: A total of 1494 DEGs were identified between eight pSS samples and 10 healthy volunteer samples. Five pyroptosis-related hub genes (AIM2, CASP1, CASP3, IL6, TNF) were recognised. DEGs were mostly enriched in immunity-related terms and several immune cells were associated with the hub genes in pSS. Among them, delta gamma T cell was significantly positively correlated with CASP3. Finally, the protein levels of these hub genes were validated to be elevated in the labial minor salivary gland biopsies of pSS patients compared to those of healthy volunteers using immunohistochemical staining. Immunofluorescence double staining further showed that IL-6, AIM2, CASP1and CASP3 were related to delta gamma T cells, and TNF was related to dendritic cells.

Conclusions: This study uncovered a significant interaction between pyroptosis and the immune microenvironment in pSS patients. Besides, we identified five pyroptosis-related hub genes that might play a role in the pathogenesis of pSS. These findings could offer valuable insights for the development of novel treatment strategies for pSS.