Clinical and experimental rheumatology最新文献

The present narrative review explores the multifactorial aetiology of rheumatoid arthritis (RA) and other immunemediated inflammatory disorders (IMIDs), emphasising the significant role of various environmental factors in disease development and exacerbation. Key modifiable environmental factors such as cigarette smoking and air pollution are identified as major contributors to RA. We will also focus on the influence of weather, seasonality, and particularly vitamin D levels, on RA activity, suggesting potential for seasonal management and supplementation to mitigate disease severity. The emerging role of diet and the gut microbiome in RA pathogenesis and progression is discussed as well, with dietary interventions and specific nutrients like omega-3 fatty acids offering protective benefits against inflammation. Despite the mounting evidence around these factors, further research is needed, to better understand the clinical impacts on RA, including well-designed randomised clinical trials.

Objectives: Autoantibodies have been described in the post-infectious state, specifically after Lyme disease and COVID-19. We aimed to describe the prevalence and potential clinical utility of several commercially available autoantibodies after these infections.

Methods: Euroimmun panels (myositis, scleroderma and ANA5) were assayed using sera from patients with Lyme disease with return to health (RTH) (n=70), post-treatment Lyme disease (n=58), COVID-19 RTH (n=47) and post-acute symptoms of COVID-19 (n=22). The post-Lyme questionnaire of symptoms (PLQS) was used to determine symptom burden after Lyme disease.

Results: There was no statistically significant difference in autoantibody prevalence across the four groups (p=0.746). A total of 21 different antibodies were found in the Lyme cohorts and 8 different antibodies in the COVID-19 cohorts. The prevalence of scleroderma-associated antibodies was higher after Lyme disease than COVID-19 (12.5% vs. 2.9%, p=0.026). There was no statistically significant difference in symptom burden based on antibody status.

Conclusions: Several autoantibodies were found after Borrelia burgdorferi and SARS-CoV2 infection, although the prevalence was similar in those with persistent symptoms and those who returned to health. While our data show no difference in autoantibody prevalence across the four post-infectious states, we do not imply that autoantibodies are irrelevant in this setting. Rather, this study highlights the need for novel antibody discovery in larger cohorts of well-defined patient populations.

Objectives: To evaluate the effectiveness of the anterior segment optical coherence tomography (AS-OCT) for the screening of anterior uveitis in children diagnosed with juvenile idiopathic arthritis (JIA).

Methods: A cross-sectional, observational, non-randomised study was conducted in JIA patients younger than 18 years. All patients underwent anterior segment (AS-OCT) and macular OCT.

Results: A total of 300 eyes of 150 patients diagnosed with JIA were included; 74% were females, and mean age was 11.12 ± 3.51 years old (range 4.13-18.60). In the slit-lamp examination, anterior uveitis was diagnosed in 16 eyes. In the AS-OCT, anterior uveitis was suspected in 27 eyes; cells were detected in 27 eyes and retrokeratic precipitates in 5 eyes. Sensitivity was 0.94 and specificity was 0.96, positive predictive value was 0.59 and negative predictive value was 0.99, and Kappa-Cohen index was 0.71.

Conclusions: AS-OCT could be considered for the screening of anterior segment uveitis in children diagnosed with JIA.

Rheumatoid arthritis (RA) is a most common chronic joint disease belonging to inflammatory autoimmune disease. The pathology of the disease is characterised by the infiltration and proliferation of fibroblast like synoviocytes (FLSs) and the destruction of the bone and cartilage matrix, which leads to joint dysfunction and even deformity.In recent years, an increasing number of studies have shown that MSCs have immunosuppressive properties and have been demonstrated in a variety of disease. Exosomes serve as carriers that mediate intercellular material transfer and information exchange and contain a variety of biologically active components such as proteins, lipids, and nucleic acids. Mesenchymal stem cell-derived exosomes (MSCs-Exos) play a regulatory role by carrying bioactive substances from the parental cells. Exos-derived from MSCs of different origins can modulate several pathological processes, such as immune inflammatory response, improvement of bone metabolism. In this research, we reviewed the current major pathogenesis of RA and explored the important role of MSCs-Exos in this disease. To be more precise, we summarised the effects of different MSCs-Exos on the pathomechanisms of RA, with a view to providing guidance and reference for future studies.

Objectives: We aimed to retrospectively evaluate retention rate and causes of discontinuation of JAKi in rheumatoid arthritis (RA) patients with particular regards to difficult-to-treat subgroups.

Methods: The diffusion of Janus kinase inhibitors (JAKi) for the treatment of RA has rapidly increased in recent years due to their effectiveness, even in difficult-to-treat subgroups of patients. After the publication of the Oral Surveillance study, the labelling of JAKi was modified, advising against their use in elderly patients and those at risk for cardiovascular events and malignancies. Demographic, clinical, serological and therapeutic characteristics of RA patients treated with JAKi were recorded, including smoking habit and comorbidities.

Results: Three hundred and thirty consecutive RA patients were enrolled in the study. Among them, 50.3% patients had previously failed at least two biologic DMARDs. Risk factors for the use of JAKi were reported in 75.5% of patients, 41.5% of them were older than 65 years, 37.6% had smoked, while 48.8% had increased cardiovascular or cancer risk. Anticitrullinated peptide antibodies (ACPA) and combination therapy with conventional synthetic DMARDs were associated with a longer drug persistence and ACPA remained independently associated to a higher retention rate of JAKi also in the subgroup of difficult-to-treat patients.

Conclusions: In conclusion, our study supports the clinical effectiveness of JAKi in RA, even in the multi-failure subgroup of patients, where the risk/benefit ratio overcomes the safety risk. The presence of ACPA and the concurrent use of + cs-DMARD may increase the survival on JAKi in the long term.

Objectives: Giant cell arteritis (GCA) is a common vasculitis affecting patients aged 50 and older. GCA leads to chronic inflammation of large/medium-sized vessel walls with complications such as permanent vision loss and risk of stroke and aortic aneurysms. Early diagnosis is crucial and relies on temporal artery biopsy (TAB) and ultrasound imaging of temporal and axillary arteries. However, these methods have limitations. Serum biomarkers as autoantibodies have been reported but with inconclusive data for their use in the clinical setting. Additionally, C-reactive protein and erythrocyte sedimentation rate are non-specific and limited in reflecting disease activity, particularly in patients treated with IL-6 inhibitors. This study aimed to identify serum autoantibodies as new diagnostic biomarkers for GCA using a human protein array.

Methods: One commercial and one proprietary human protein array were used for antibody profiling of sera from patients with GCA (n=55), Takayasu (TAK n=7), and Healthy Controls (HC n=28). The identified candidate autoantigens were purified and tested for specific autoantibodies by ELISA.

Results: Antibodies against two proteins, VSIG10L (V-Set and Immunoglobulin Domain Containing 10 Like) and DCBLD1 (discoidin), were identified and found to be associated with GCA, with an overall prevalence of 43-57%, respectively, and high specificity as individual antibodies. A control series of TAK sera tested negative.

Conclusions: Detecting GCA-specific autoantibodies may offer a new, non-invasive tool for improving our diagnostic power in GCA. Even though cell-mediated immune responses are crucial for GCA pathogenesis, this finding opens the way for investigating the additional role of humoral immune responses in the disease.

Objectives: We aimed to study whether myocardial changes are already detectable by cardiac magnetic resonance (CMR) imaging at the time of rheumatoid arthritis (RA) diagnosis.

Methods: This single-centre prospective study included 39 treatment-naive patients with early rheumatoid arthritis (ERA, symptom duration <1 year) without any history of heart disease, and 38 age- and sex-matched healthy volunteers. The disease severity was assessed with clinical evaluation (Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP) score) and serological testing (rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA)). The ERA patients were classified into group A (DAS28-CRP score ≥3.2, positive RF and ACPA; n=17) and group B (not fulfilling the group A criteria). The ERA patients and healthy controls underwent 1.5T CMR.

Results: Group A patients had significantly higher myocardial global T1 relaxation times than the healthy controls, 987 [965, 1003] ms vs. 979 [960, 991] ms (median [IQR]; p=0.041). A significant difference in T1 was found in the basal, mid inferior and mid anterolateral segments. In a multivariate analysis, prolonged global T1 relaxation time was independently associated with female sex (95% CI [5.62, 51.31] ms, p=0.016), and group A status (95% CI [4.65, 39.01] ms p=0.014).

Conclusions: At the time of diagnosis, ERA patients with a higher disease activity (DAS28-CRP score ≥3.2) and both positive RF and ACPA showed prolonged T1 relaxation times in basal myocardial segments. These segments could be most susceptible to the development of myocardial fibrosis, and a segmental reporting style could be useful when estimating the first signs of myocardial fibrosis.

Objectives: Age has a significant impact on systemic lupus erythematosus (SLE). However, data on very late-onset SLE (vlSLE) are scarce. We have compared the clinical and serological features of vlSLE patients with younger-onset patients.

Methods: We assessed the clinical and laboratory data of all patients fulfilling SLE classification criteria evaluated at a university hospital from 1978 to 2023. Patients were divided into 4 groups according to age at diagnosis: juvenile SLE (jSLE <8 years); adult SLE (aSLE 18-49 years); late SLE (lSLE 50-59 years); vlSLE (≥60 years).

Results: 845 patients were enrolled. The jSLE, aSLE, lSLE, and vlSLE groups included 153, 630, 47, and 15 patients, respectively. The vlSLE group tended to have a lower female-to-male ratio (4:1; p=0.282), was mainly Caucasian (93.3%; p<0.001), and had the lowest survival time (20.3 years; p<0.001). vlSLE patients had the lowest prevalence of positive anti-dsDNA antibodies (26.7%; p=0.010) and low C3 levels (13.3%; p<0.001). Although arthritis was less common among vlSLE patients (73.3%; p=0.043), they more commonly developed Sjögren's syndrome (SS 33.3%; p<0.001) and rheumatoid arthritis (RA 13.3%; p<0.001). Infections and malignancy were the main causes of death.

Conclusions: Compared with younger patients, in vlSLE, female predominance is less pronounced. Arthritis, anti-dsDNA antibodies and low C3 levels are less frequent. SS and RA are more common. Despite lower disease activity, vlSLE patients have the lowest survival rate. While uncommon, SLE should not be excluded as a possible diagnosis in the elderly.

Objectives: To explore the risk factors of anxiety and depression, especially their association with serum autoantibodies, in patients with connective tissue diseases (CTDs).

Methods: Three hundred and fifty-two inpatients with CTDs were recruited and their demographic, serological and imaging data were collected through the medical record system. Depression and anxiety were assessed by the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) respectively. Analysis of variance (ANOVA), rank sum test, chi-square test and logistic regression were performed to investigate risk factors for depression and anxiety.

Results: The prevalence of depression (PHQ-9 ≥ 5) and anxiety (GAD-7 ≥5) in CTD patients was significantly higher than that in the Chinese general population (depression: 44.3% vs. 32.2%, anxiety: 39.5% vs. 22.2%). Sleep time was a protective factor for both depression and anxiety (OR=0.734, 95% CI: 0.616~0.874, p<0.001 and OR=0.684, 95% CI: 0.559~0.835, P<0.001, respectively) while anti-Ro52 antibody was a risk factor for them (OR=5.466, 95% CI: 2.978~10.032, p<0.001 and OR=4.075, 95% CI: 2.073~8.010, p<0.001, respectively). Further analysis showed that anti-Ro52 antibody was a risk factor for depression and anxiety in all four subgroups, namely SLE, SS, RA, and other CTDs.

Conclusions: Anti-Ro52 antibody is probably a risk factor for depression and anxiety in patients with connective tissue diseases. CTD patients with the presence of anti-Ro52 antibody are more prone to depression and anxiety than those without it.

Objectives: The disruption of the NKG2D-MICA axis can induce an enhanced immune response and promote autoimmune processes during axial spondyloarthritis (axSpA) pathogenesis. We aimed to investigate potential relationships between selected single nucleotide polymorphisms within the MICA and NKG2D genes and disease susceptibility and clinical parameters in axSpA patients treated with TNF inhibitors.

Methods: Genotyping of MICA rs1051792 and NKG2D rs1154831, rs1049174, and rs2255336 was performed in 163 axSpA patients and 234 healthy controls using a real-time PCR method.

Results: MICA rs1051792 A allele was more common in patients than in controls (p<0.0001). Patients with the AA genotype showed greater disease activity score (BASDAI) after three (p=4×10-4) and six (p=0.032) months of treatment compared to G carriers. After three months of therapy with anti-TNFs, the MICA AA homozygosity occurred more often in non-responsive or moderately responsive patients than good responders with the same genotype (p=1×10-4). Additionally, patients bearing the NKG2D rs1154831 CC genotype demonstrated lower BASDAI scores (p=0.035) and were significantly more common among subjects with a good outcome (p=0.004) after six months of treatment.

Conclusions: These results suggest that MICA and NKG2D gene polymorphisms may be biomarkers associated with disease susceptibility and clinical outcomes after anti-TNF therapy in axSpA patients and imply a rather less favourable effect of the MICA A and NKG2D G genetic variants.