Clinical and experimental rheumatology最新文献

Objectives: To investigate gut microbial alteration and their functional consequences in obesity (OB)-related knee osteoarthritis (OA) by integrating microbiome with metabolomic, proteomic, and dietary data.

Methods: Fecal and fasting plasma samples were collected from 91 knee OA patients and 12 OA-free controls, classified into four subgroups based on OB and OA status: 66 OB+OA+, 25 OB-OA+, 5 OB+OA-, and 7 OB-OA-. 16S rRNA gene sequencing was performed to profile gut microbiota. MaAsLin2 modelling was applied, and dietary intake was incorporated into the models. Plasma metabolomics (n=630 metabolites) and proteomics (n=5,416 proteins) were integrated with microbial signatures to assess functional associations.

Results: OB+OA+ patients exhibited significantly lower a- and β-diversity than OB-OA+ (p<0.05). Seventeen microbial taxa were identified to be significantly associated with OB+OA+ (all p<7.65×10-5 after correcting tests for 654 ASVs), and 16 of them remained significant after adjustment for age, sex, antibiotic use, and dietary intake. PICRUSt2-based predictive analysis on these taxa suggested that bile acid biosynthesis was upregulated in OB+OA+ group. These taxa were correlated with 376 metabolites (p<0.05) with enrichment in fatty acid biosynthesis, linoleic/arachidonic acid metabolism, and propanoate metabolism pathways. They were also associated with 146 proteins (p<0.001) with enrichment in PI3K-Akt signalling, ECM-receptor interaction, and lipid/atherosclerosis pathways.

Conclusions: OB+OA+ patients exhibited significant gut microbial dysbiosis associated with systemic metabolic and proteomic alterations relevant to OA pathophysiology. The microbiome-metabolome-proteome axis may provide mechanistic insights into worsened OA outcomes in OB individuals and could inform microbiome-targeted interventions.

Objectives: To characterise the clinical spectrum of adult parvovirus B19 (B19V) infection referred for rheumatologic evaluation and to identify clinical predictors of arthritis resolution.

Methods: We conducted a multicentre retrospective study across nine Italian rheumatology units during the 2023-2024 post-pandemic resurgence of B19V infection. Clinical, therapeutic, and follow-up data were systematically collected using a standardised REDCap platform.

Results: We enrolled 71 patients (median age 43 years; 72% female), 85% with a confirmed diagnosis. Most reported recent household exposure. Joint involvement was nearly universal (96%), predominantly oligoarticular, and often affected large joints, mimicking early inflammatory arthritis. Fever (65%) and skin manifestations (61%) were frequent. In addition to typical exanthems, 9 patients displayed a distinctive purpuric rash confined to the pretibial region, sparing ankles and feet - a potentially distinctive feature of to B19V infection. Symptom resolution occurred in 87% of cases, usually within one month. Glucocorticoid use was independently associated with - but not proven to cause - faster resolution in Cox regression (HR 0.53; 95% CI: 0.31-0.90; p=0.020), though this finding may reflect indication bias. No other clinical or serological predictors emerged.

Conclusions: This study provides the largest systematically collected multicentre cohort of adults with B19V infection referred to rheumatology during the post-pandemic European outbreak. Our findings expand the clinical spectrum of B19V arthritis and highlight distinctive skin patterns that may aid differential diagnosis during epidemic waves.

Objectives: Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory condition that may affect any organ. Prostatic involvement is uncommon and under-recognised. The presentation often mimics benign prostatic hyperplasia or prostate carcinoma, causing diagnostic uncertainty. This systematic review synthesises evidence on IgG4-related prostatitis, focusing on clinical manifestations, diagnostic approaches, treatment, and outcomes.

Methods: Following PRISMA 2020 guidelines, PubMed, Scopus, Web of Science, and Ovid were searched from inception to 12 February 2025. Eligible studies included English-language case reports, case series, and observational studies describing prostatic involvement in IgG4-RD. Data on demographics, clinical and laboratory findings, management, and outcomes were extracted and analysed descriptively.

Results: Fifty studies reporting 66 cases were included. Median age was 64 years (range 20-82). Serum IgG4 concentrations were elevated in most (median 832 mg/dL, range 5-4,500), while prostate-specific antigen (PSA) levels varied widely (0.01-180 ng/mL). Multiorgan involvement occurred in 57.8%, isolated disease in 6.2%. Lower urinary tract symptoms were most frequent (39.6%). Glucocorticoids, mainly prednisone, were the main therapy (69.2%), followed by surgery, chiefly transurethral resection of the prostate. Complete and partial responses occurred in 50.9% and 43.4%. Treatment type correlated with outcome (χ²=49.70; p<0.001). Malignancy (18.5%) was associated with higher mortality (p=0.028).

Conclusions: IgG4-related prostatitis is a rare and likely under-recognised manifestation of IgG4-RD. Its overlap with benign and malignant prostatic disorders delays diagnosis. Serum IgG4 and PSA are unreliable markers of disease and monitoring. Glucocorticoids remain first-line therapy, with surgery in obstructive cases. Multicentre studies are needed to define prevalence, natural history, and optimal management.

Objectives: Inclusion body myositis (IBM) is a disorder with features of both inflammation and degeneration yet without effective treatment. Influences of the gut microbiome on degenerative as well as inflammatory disorders and immune treatments are known. We sought to investigate whether the gut microbiome might influence the development or recalcitrance of IBM.

Methods: We appealed to IBM patients and their unaffected spouses/cohabitants for stool samples and data on clinical symptoms, gathering questionnaire data (modified Gastrointestinal Symptom Rating Scale (mGSRS), IBM Functional Rating Scale (IBMFRS) and Bristol Stool Scale) and stool samples for 16S rRNA V3V4 metagenomic analysis from 21 IBM and 20 control probands. Bioinformatic analyses used QIIME2 and MicrobiomeAnalyst software packages. LEfSe and Random Forest analysis aimed to identify group specific biomarkers. PICRUSt was used to perform pathway analysis.

Results: No overall differences of alpha and beta diversity were found between IBM and control group. No impact of immune treatments was found, but a reduction in alpha diversity was identified comparing older (≥ 72 years) IBM and control probands. Increased abundances of some genera, in particular Bacteroides, were detected in the IBM group. Bacteroides, Clostridium CAG 352, and Eggerthella were identified as IBM biomarkers at genus level. Gastrointestinal symptoms (mGSRS) correlated with disease severity (IBMFRS).

Conclusions: General differences of gut microbiome seem unlikely to play a role in the genesis of IBM. Whether the late occurring or the more specific differences detected are part of the disease course needs to be addressed by investigations of further biosamples.

Objectives: Anti-signal recognition particle antibody immune-mediated necrotising myopathy (anti-SRP-IMNM) is characterised by prominent muscle weakness and poor neurological outcomes. This study aimed to evaluate the relationship between endomysial fibrosis and the clinical, muscle magnetic resonance imaging (MRI) and myo-pathological features of patients with anti-SRP-IMNM.

Methods: We collected the clinical, imaging, and myo-pathological data of patients diagnosed with anti-SRP-IMNM. Differences between patients with and without increased endomysial fibrosis on muscle biopsy were compared.

Results: Ninety-four patients were included in the study, comprising 12 paediatric and 82 adult patients. The mean age at onset was 41.2±17.3 years. The mean serum creatinine kinase concentration was 6885.8±6300.7 IU/L. MRI revealed muscle oedema in 87.3% of patients and fatty infiltration in 77.5%, which was particularly severe in the muscles of the posterior thigh. Endomysial fibrosis was found in 50% of patients and was significantly associated with early onset (p=0.004), paediatric age (p=0.044), muscle fatty infiltration on MRI of the thigh (p=0.045), and inflammatory cell infiltration on pathology (p<0.05).

Conclusions: In anti-SRP-IMNM, endomysial fibrosis may be the pathological basis of fatty infiltration observed on MRI and may be associated with resistance to immunotherapy.

Objectives: Familial Mediterranean fever (FMF) requires lifelong colchicine therapy, yet suboptimal adherence remains a major challenge. Illness perception shaped by psychological representations of disease may affect adherence. This study aimed to investigate illness perception and adherence association in adult Turkish patients with FMF.

Methods: This cross-sectional study included 304 adult FMF patients followed at Kartal Dr. Lutfi Kirdar City Hospital between 2022 and 2024. Medication adherence and illness perception were evaluated by Medication Adherence Scale for FMF (MASIF) and the Brief Illness Perception Questionnaire (Brief-IPQ). Demographic, clinical, and laboratory data were collected. Statistical analyses included chi-square, t-test, Mann-Whitney U test, correlation analysis and multivariate logistic regression.

Results: The cohort included 210 (69.1%) females and 94 (30.9%) males with a mean age of 35.8±12.1 years. Overall, 75.3% of patients showed good adherence, with a mean MASIF score of 67.1±9.6. Median Brief-IPQ score was 44 (IQR 16.0), the highest in the "timeline" domain and the lowest in "illness comprehensibility". A significant negative correlation was found between MASIF and Brief-IPQ scores (r=-0.374, p<0.001). Patients with good adherence had significantly lower illness perception scores, particularly in "personal control", "treatment control" and "illness comprehensibility" domains (p<0.001). Multivariate logistic regression confirmed these domains as independent predictors of adherence.

Conclusions: Medication adherence among adult Turkish patients with FMF was relatively high but closely influenced by illness perception. Patients with clearer disease understanding and positive control beliefs demonstrated better adherence. Addressing illness perception through education and psychosocial support may enhance adherence and improve long-term outcomes in FMF.

Objectives: The objective of this study is to assess the differences in environmental exposures of juvenile dermatomyositis (JDM) patients in Brazil versus United States (U.S.).

Methods: JDM patients from 4 centres [3 U.S. (n=66), 1 Brazil (n=36)] were enrolled. Exposures during pregnancy were assessed by questionnaire, including occupational exposures, sources of inhalable pollution near the mother's home and work, and exposure to tobacco/alcohol.

Results: JDM mean age onset was 7.12 (SD±4.02) years for U.S. patients and 5.30 (SD±2.52) for Brazilians (p=0.004). During pregnancy, American mothers more frequently worked outside home than Brazilians (65.2% vs. 41.2%; p=0.032). Americans more often worked in offices (51.2% vs. 14.3%; p=0.027) and Brazilians, as teachers (28.6% vs. 4.8%; p=0.029). Americans commuted to work more frequently by subway (68.3% vs. 7.1%; p=<0.01), Brazilians, by bus (64.3% vs. 14.6%; p=0.001). Brazilians were more frequently exposed to dust (42.9% vs. 9.5%; p=0.01) and tobacco (50% vs. 23.1%; p=0.01). Places where Brazilians worked (35.7% vs. 9.1%; p=0.03) and lived (50% vs. 10.6%; p=<0.01) during pregnancy were closer to factories and quarries, as well as where the child was born (32.3% vs. 8.6%; p=0.007). After birth, Brazilian patients were more frequently exposed to tobacco, both through their fathers' smoking (26.5% vs. 6.2%; p=0.009) and other household residents (36.4% vs. 9.2%; p=0.002).

Conclusions: Earlier onset of symptoms, possibly related to early life environmental exposures, was observed in Brazilian patients. Their mothers lived and worked closer to factories and quarries, commuted to work by bus and were more exposed to dust and tobacco.

Objectives: The aim of this study is to investigate the frequency and functional changes of mucosal-associated invariant T (MAIT) cells in the peripheral blood of patients with dermatomyositis (DM).

Methods: Peripheral blood mononuclear cells (PBMCs) from 23 untreated DM patients and 32 healthy controls (HC) were analysed via flow cytometry to assess MAIT cell frequency, activation status, chemokine receptor expression, and cytokine production.

Results: The frequency of circulating MAIT cells was significantly decreased in the DM group compared with the HC group, while the proportion of CD69+ and PD-1+ MAIT cells was significantly increased, especially in patients with melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5-DM). Moreover, the expression of the chemokine receptors CCR2 and CCR5 on MAIT cells was reduced in DM patients. In addition, the proportion of IFN-γ+ MAIT cells was significantly elevated in DM patients.

Conclusions: The reduced frequency of MAIT cells in DM may be associated with excessive activation. The increased secretion of IFN-γ by MAIT cells may contribute to DM pathogenesis.

Objectives: This study aimed to evaluate the effectiveness of the SARS-CoV-2 vaccination program in systemic sclerosis (SSc) patients treated by Autologous Hematopoietic Stem Cell Transplantation (AHSCT) compared to non-AHSCT SSc patients.

Methods: A French retrospective case-control study was conducted in SSc patients eligible for SARS-CoV-2 vaccination. AHSCT SSc (cases) were matched 1:1 with non-AHSCT SSc (controls) patients by age, sex, and disease duration. The primary endpoint was to assess the cumulative incidence of COVID-19 infection. Secondary objectives evaluated vaccination acceptance, the onset of severe adverse events after SARS-CoV-2 vaccination, the severity of COVID-19 infection and the serological response after vaccination or not.

Results: Seventy-two SSc patients (36 AHSCT 1:1 matched to 36 non-AHSCT, on age, sex, and disease duration on 1 January 2021) were included. The study showed a higher incidence of COVID-19 infection in AHSCT (p=0.007) versus non-AHSCT SSc patients, with respectively 11 out 36 cases and 2 out 36 controls contracting mild to moderate infections. The vaccine acceptance rate did not differ between AHSCT and non-AHSCT SSc patients, with respectively 5 out 36 cases and 3 out 36 controls who refused vaccination. No severe adverse event was reported after SARS-Cov-2 vaccination. Serological responses did not significantly differ between the two groups.

Conclusions: The incidence of COVID-19 infection was higher in AHSCT-SSc compared to non-AHSCT SSc patients, with no difference in vaccine acceptance rate. COVID-19 vaccination in AHSCT highly fragile patients appeared to provide substantial COVID-19 protection, as shown by their favourable clinical evolution and effective humoral response.