Clinical and experimental rheumatology最新文献

Objectives: Glucocorticoids (GC) are important in the treatment of autoinflammatory disorders. Oral prednisolone ≤5 mg/day can be effective, but such doses are at or even below physiological daily endogenous GC production. We hypothesised that their immunosuppressive effect might be explained by high hepatic bioavailability of oral GC, exposing the liver to supraphysiological GC via the portal circulation. We tested this by comparing the effect of oral versus subcutaneous low-dose prednisolone, on erythrocyte sedimentation rate (ESR).

Methods: Patients with rheumatoid arthritis or psoriatic arthritis, elevated ESR (≥30 mm/h) and no current or recent GC therapy were eligible. In a pilot study (n=5), 5 mg/day oral prednisolone decreased ESR significantly, suggesting a sample size of 10 patients for a randomised, non-blinded crossover trial. Patients received 5 mg/day prednisolone for 2 periods of 4 days: one treatment period orally and one subcutaneously with a 10-day washout period between treatments. ESR was measured before (day 1 and 15) and after (day 5 and 19) each treatment course.

Results: 10 patients were included. ESR decreased after both oral and subcutaneous prednisolone, by -5.6 (20.9) and -5.8 (3.0) mm/h, respectively (p=0.98). The treatment order had no effect on the outcome.

Conclusions: . Short-term oral low-dose GC therapy is not more effective than parental GC in decreasing ESR, arguing against therapeutic high hepatic bioavailability effects. More likely, systemic concentration peaks following administration explain why oral physiological steroid doses are clinically effective.

Myositis-specific autoantibodies (MSAs) are hallmarks of idiopathic inflammatory myopathies (IIMs) and have become increasing valuable in disease diagnosis, phenotyping, and classification. In addition to their clinical utility, emerging data, including findings from several animal studies, suggest that MSAs and autoreactive T cells substantially contribute to the etiopathogenesis of IIMs. This review aims to provide an updated perspective on myositis autoantibodies by focusing on relevant clinical and translational studies.

Objectives: The Janus kinases-signal transducer and activator of transcription (JAK-STAT) signalling pathway plays a crucial role in autoimmunity and the signalling pathways of many cytokines in Sjögren's disease (SjD). Therefore, the aim of this study was to investigate both the therapeutic and immunomodulatory effects of the oral JAK3/JAK2/JAK1 inhibitor tofacitinib in a murine model of SjD.

Methods: Tofacitinib or vehicle was administered orally to the mice with SjD for 6 weeks. Salivary flow rate was measured every three weeks. Pathological changes of salivary gland were detected by haematoxylin-eosin staining, and the percentages of subsets of CD4+ T cells and B cells in the cervical lymph nodes (cLNs) and spleen was determined by flow cytometry.

Results: Tofacitinib significantly ameliorated submandibular gland inflammation compared to the control group, as evidenced by reduced lymphocytic infiltration. Salivary flow rates improved significantly in tofacitinib treated mice compared to controls, indicating restored salivary gland function. The treatment also led to a substantial decrease in follicular helper T (Tfh) cells and the Tfh/Treg ratio in both the spleen and cLNs. Additionally, the frequencies of T helper 1 (Th1) and T helper 17 (Th17) cells were reduced in the spleen and cLNs.

Conclusions: Our data indicated that tofacitinib reduced percentages of effector T cells in an animal model of SjD. In addition, tofacitinib alleviated salivary gland inflammation and hypofunction, offering new insights into the clinical management of SjD.

Objectives: The purpose of this study was to evaluate the performance of a dermatologist-filled-in 7-item questionnaire (called HERACLES) as a screening tool for psoriatic arthritis (PsA) in patients with psoriasis.

Methods: This study was performed in Italy in seven dermatology centres cooperating with rheumatology centres. Adults with psoriasis were consecutively recruited up to a calculated number of 750. They were invited to fill in the following questionnaires used for PsA screening: ToPAS, PASE, PEST, and EARP. The dermatologists, in addition to standard demographic and clinical data, scored each participant using a new 7-item questionnaire. All participants were later evaluated by the rheumatologists for a diagnosis of PsA. The performance of the various questionnaires was compared using receiver-operating-characteristic (ROC) area-under-the-curve (AUC) analysis.

Results: Of the 759 enrolled psoriatic patients, 524 (280 males and 244 females) were suitable for data analysis. PsA was diagnosed in 73 (13.9%) participants. PsA and non-PsA patient characteristics were comparable, except for arthritis-related features which were often more prevalent in the PsA group. The ROC AUC of the HERACLES instrument was 0.775 (CI: 0.722-0.828), similar to that of the other questionnaires (ToPAS 0.757; PASE 0.730; PEST 0.741; and EARP 0.739). For the HERACLES instrument, a score value of 2 yielded a sensitivity of 92% and a specificity of 47%.

Conclusions: In this study, a dermatologist-filled-in questionnaire proved to be not inferior to patient-administered PsA screening tools and to be feasible. It might be an alternative (or additional) tool to screen psoriatic patients for rheumatology referral.

Objectives: Utilising Patient-Reported Outcomes Measurement Information System (PROMIS®) questionnaires can enhance clinical care by measuring longitudinal changes in symptom severity as reported by the patient. The aim of this pilot study was to assess the feasibility and impact of incorporating PROMIS® questionnaires at the point-of-care in rheumatology practice.

Methods: Patients with rheumatic diseases and decrements in ≥1 PROMIS® domain (pain intensity, physical function, or sleep disturbance) were stratified by their concerning domain, then randomised to either receive an interpretation of their PROMIS® scores prior to their rheumatology appointment (Arm 1) or to usual care (Arm 2) (ClinicalTrials.gov ID: NCT05026853). The primary outcome was the documentation of PROMIS® scores in the electronic medical record (EMR). Secondary outcomes include recommendations made by physicians based on PROMIS® scores, patient-provider communication, and change in the most concerning PROMIS® domain score from baseline to 12 weeks.

Results: 110 patients were enrolled. 55 were randomised to receive report cards (Arm 1), of which 46 received the report card, and 55 received usual care (Arm 2). Documentation of PROMIS® scores in the EMR was 50% higher in Arm 1 (12.7% in Arm 2, p<0.0001). More recommendations were made based on PROMIS® scores for Arm 1 patients. There was no significant difference in post-visit PROMIS® score improvement between Arm 1 and Arm 2.

Conclusions: Providing PROMIS® report cards to patients and healthcare providers increased score documentation in the EMR. Increased recommendations made based on PROMIS® scores in Arm 1 suggest that having a score interpretation might help direct medical decision-making.

Objectives: Complicated primary Sjögren's syndrome (pSS) with haematological involvement (HI) is not uncommon; however, the aetiology of this condition remains obscure. The clinical characteristics, cytokine levels, and expression of peripheral blood lymphocyte subsets (CD4+ T lymphocyte subsets in particular) of patients with pSS-HI were investigated in this study.

Methods: The pSS-HI group (n = 43), the pSS complicated without HI (pSS-non-HI) group (n = 94), and the healthy controls (HCs) group (n = 40) were enrolled in the Second Hospital of Shanxi Medical University. The clinical data were gathered, and cytokines and peripheral blood lymphocyte subsets were quantified using flow cytometry and the Cytometric Bead Array (CBA), respectively.

Results: Patients with pSS-HI were more likely than those without pSS-HI to develop skin involvement, had a higher positive rate of anti-SSA antibody, and had elevated levels of IgA, IgG, and ESR. Compared to the pSS-non-HI group, the number of all lymphocyte subsets was lower in the pSS-HI group. However, the proportion of Th2 cells in the pSS-HI group was higher than those in the pSS-non-HI group. In contrast to the pSS-non-HI group, the pSS-HI group exhibited elevated levels of IL-10 and decreased levels of IL-4. A significant correlation was observed between IL-10 and the number of total T cells, CD4+ T cells, CD8+ T cells, NK cells, Th1 cells, Th2 cells, and Th17 cells. In the context of pSS-HI, protective factors may include the number of Treg cells and CD4+ T cells, whereas risk factors may include IgA and the number of Th2 cells.

Conclusions: An immunological mechanism potentially implicated in the development of pSS-HI may be the elevation of IL-10 and the reduction of peripheral blood CD4+ T cell subsets (particularly Treg cells) and serum IL-4 levels.

Objectives: To elucidate the existence of bacteria in situ and its influence on the clinical and pathological features of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.

Methods: A total of 34 patients diagnosed with SAPHO syndrome were allocated to two groups (bacterial positive and bacterial negative) based on next-generation sequencing (NGS) and microbiological culture through CT guided percutaneous puncture. The clinical characteristics, biochemical markers, imaging data, and pathological results of the patients were analysed and compared between the two groups. And 32 infectious suppurative osteomyelitis patients were also included in this study to compare the pathological results with SAPHO syndrome patients.

Results: The positive rate of bacteria by NGS and bacterial culture were 41.2%, respectively. And the two methods detected a wide variety of bacterial species, including cocci, bacilli, and others. The difference of clinical symptoms (such as pain, swelling, and warmth), biochemical markers, imaging findings and pathological findings were not statistically significant between the bacteria positive and the bacteria negative groups. Moreover, patients with SAPHO syndrome had less inflammatory cell infiltration and increased granulation tissue formation compared with infectious suppurative osteomyelitis patients.

Conclusions: NGS and bacterial culture expand the variety of detectable bacteria and improve the detection rate of bacteria in SAPHO syndrome. The bacteria in SAPHO patients may be low-virulence colonising bacteria presented in the skin or in the body. The less inflammatory cell infiltration in tissue may reflect a damaged ability to clear low-virulence bacteria in patients with SAPHO syndrome. The presence of low-virulence bacteria may provide a new therapy choice for refractory SAPHO patients.

Objectives: To compare the involvement of cytotoxic CX3CR1+ T cell subsets between giant cell arteritis (GCA) and Takayasu's arteritis (TAK).

Methods: We examined the proportions of CX3CR1+ CD4+ and CD8+ T cells in whole blood freshly obtained from 30 treatment-naive patients with active large vessel vasculitis (GCA, n=22 and TAK, n=8) and 16 healthy controls (HC). Infiltration of CX3CR1+ T cells into the affected arteries was assessed using immunohistochemical staining. Furthermore, CX3CR1+ CD4+ and CD8+ T cells were followed up after glucocorticoid treatment for longitudinal assessment of both diseases.

Results: The proportion of CX3CR1+ CD4+ T cells was significantly higher in GCA than in HC but not in TAK. No differences were observed in the proportions of CX3CR1+ CD8+ T cells among the GCA, TAK, and HC groups. The increased proportion of CX3CR1+ CD4+ T cells in GCA strongly correlated with the severity of systemic inflammation, whereas no significant correlation was found in TAK. Compared to TAK, CX3CR1+ CD4+ T cells from GCA patients showed significantly higher expression of granzyme B and perforin. The inflamed temporal arterial tissues of the GCA were infiltrated by numerous CX3CR1+ T cells, contributing to inflammation, disruption of the elastic lamina, and intimal hyperplasia. In contrast, no infiltration of CX3CR1+ T cells was observed in the aortitis lesions of TAK. Longitudinal analysis of post-glucocorticoid treatment showed a reduction in CX3CR1+ T cells in GCA, whereas no significant change was observed in TAK.

Conclusions: Differences in immune mechanisms between GCA and TAK highlight cytotoxic CX3CR1+ T cells as potential drivers for GCA-related inflammation and vessel damage but not for TAK.

Objectives: In this study, we investigated whether serum Wnt3A levels at diagnosis reflected cross-sectional activity and predicted poor outcomes during follow-up in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).

Methods: This study included 80 patients who were newly diagnosed with AAV at a tertiary hospital. At diagnosis, whole blood was obtained from patients and sera was immediately isolated and stored at -80℃. Moreover, AAV activity was assessed using the Birmingham Vasculitis Activity Score (BVAS), and a high BVAS was defined as the highest tertile. Poor outcomes including all-cause mortality and end-stage kidney disease (ESKD) were recorded.

Results: The patients had a median age of 63.5 years, with 40% being male and 60% female patients. Serum levels of Wnt3A at diagnosis were correlated with the cross-sectional BVAS and serum Wnt3A ≥411.7 pg/mL exhibited an increased risk of high BVAS. In addition, serum Wnt3A levels at diagnosis significantly correlated with cross-sectional acute-phase reactants and serum albumin levels. Furthermore, serum Wnt3A levels at diagnosis were associated with AAV exacerbation, leading to ESKD. Particularly, serum Wnt3A ≥407.1 pg/mL also demonstrated an elevated risk of ESKD (relative risk 3.867). Additionally, patients with serum Wnt3A ≥407.1 pg/mL exhibited a significantly lower cumulative ESKD-free survival rate than those with lower serum Wnt3A levels.

Conclusions: This study is the first to demonstrate the clinical potential of serum Wnt3A levels at diagnosis for estimating cross-sectional activity and partially predicting the advancement to ESKD during follow-up in patients with AAV.