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.

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.

Objectives: N-acetylcysteine (NAC) is used in Sjögren's disease (SjD) based on limited evidence. The aim of this study was to assess the efficacy of NAC for relieving dryness symptoms in SjD.

Methods: In this placebo-controlled double-blind trial, 60 adult SjD females (with low disease activity) were randomised to receive NAC (1,200 mg/day orally) or placebo. At baseline (D0), 30 days (D30) and 90 days (D90), all participants underwent the following evaluations: EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Ocular Surface Disease Index (OSDI), Xerostomia Inventory (XI), Leicester Cough Questionnaire (LCQ), unstimulated/stimulated salivary flow, Schirmer's test, and plasma levels of thiobarbituric acid reactive substances (TBARS), glutathione and NAC.

Results: At inclusion, both groups were balanced for age, ethnicity, disease duration, ESSPRI, OSDI, XI, Schirmer's test, salivary flow, ESSDAI and topical/systemic treatments (p>0.05). No significant differences were observed between NAC and placebo groups on D30 and D90 regarding ESSPRI, XI, OSDI, LCQ, Schirmer's test, stimulated salivary flow, ESSDAI and topical/systemic treatments (p>0.05). Unstimulated salivary flow was significantly higher in the placebo group on D90 (p=0.018). NAC blood concentrations were significantly higher in the NAC group on D30 (p=0.018) and D90 (p<0.001), however, no differences were found in TBARS and glutathione. Further analysis showed decrease≥1 in ESSPRI in the NAC compared with placebo group on D30 (p=0.045), a result not found on D90 (p=0.696).

Conclusions: NAC is recommended as a rescue therapy for SjD. However, our well-designed study provides novel evidence demonstrating its inefficacy for improving dryness symptoms or reducing oxidative stress.

Clinicaltrials: gov-NCT04793646.

Objectives: To assess if isolated mouth or eye dryness constitutes distinct clinical phenotypes in Sjögren's disease (SjD).

Methods: We analysed 1765 patients meeting the 2016 ACR-EULAR SjD criteria, followed up at four centres in Greece and Italy (Universities of Pisa, Italy, and Athens, Harokopion, and Ioannina, Greece). Patients with isolated mouth or eye dryness were identified and matched 1:2 with those experiencing both symptoms, according to age at SjD diagnosis, gender, and disease duration. We defined two study groups: a) patients with ocular dryness only, and b) patients with oral dryness only, based on the AECG validated questionnaires for dryness. We compared glandular and extra-glandular manifestations, serology, and histologic features between each study and their matched controls.

Results: Seventy-two patients with isolated ocular dryness and 74 with isolated oral dryness were compared with 144 and 148 matched controls, respectively. Both groups had a median disease duration of 3 years. Patients with isolated eye dryness had lower frequency of salivary gland enlargement (35.4% vs. 28.7%, p=0.05) and lymphoma (0% vs. 11.3%, p=0.001). Conversely, those with isolated oral dryness had lower rates of arthralgias (39.1% vs. 65.5%, p=0.0003) and arthritis (8.6% vs. 20.3%, p=0.05). Isolated oral dryness was associated with older age at SjD diagnosis (median 53.5 vs. 46, p=0.005) and a higher likelihood of lymphoma (9.4% vs. 0%, p=0.01) compared to isolated ocular dryness.

Conclusions: Isolated ocular or oral dryness occurs in 8% of the general SjD population. Patients with isolated dry eyes have a lower prevalence of lymphoma compared to those with isolated dry mouth.