Clinical and experimental rheumatology最新文献

Left ventricular diastolic dysfunction (LVDD) plays a central role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF), a major manifestation of heart failure (HF). Low-grade inflammatory reaction is the key mechanism leading to LVDD. Rheumatoid arthritis (RA) is a systemic inflammatory disease and affects 0.5-1.0% of the adult population. Several epidemiologic studies find that the risk of LVDD is increased in RA than in the general population. Since inflammation plays an important role in the pathogenesis of LVDD and RA is a disease characterised by chronic systemic inflammation. RA may be involved in the occurrence and development of LVDD. This review summarises the pathogenesis, predictors, and management of LVDD in patients with RA.

Objectives: Antiphospholipid syndrome (APS) is an autoimmune disease combining the occurrence of thrombotic and/or obstetric events with the persistent presence of antiphospholipid antibodies (i.e. lupus anticoagulant (LA), anti-cardiolipin (aCL) and anti-beta-2-glycoprotein I (aβ2GPI) antibodies). Among the autoantibodies regularly found in patients with APS, antiphosphatidylserine/prothrombin (anti-PS/PT) antibodies seem promising because of their high correlation with LA positivity. The main objective of this study was to characterise the population of anti-PS/PT and/or anti-PT-antibody-positive patients in terms of APS severity and organ damage.

Methods: We performed a prospective, monocentric, descriptive study of patients who had a dosage of IgG and IgG anti-PS/PT between March 2019 and May 2020. Clinical and biological data were collected from 148 patients, 128 had thrombosis including 64 with known APS according to the Sydney criteria, and 20 patients with antiphospholipid-antibody positivity (mainly LA positivity) without clinical manifestation of APS. Cases with active neoplasia including myeloproliferative disorders at the time of inclusion were excluded.

Results: Anti-PS/PT positive patients did not display any particular thrombotic phenotype but had significantly more renal impairment (renal failure p=0.01 and proteinuria p=0.04), migraine (p=0.03), and thrombocytopenia (p=0.001) than negative patients, notably in the associated-APS patient group. Moreover, tetra-positivity (LA+, aCL+, a2βGPI+, and anti-PS/PT+) was associated with more severe APS (thrombotic recurrences, thrombosis under anticoagulant treatment, and a trend of more frequent catastrophic antiphospholipid syndrome). To a lesser extent, a similar phenotype was observed with anti-PT antibody positivity, but the 58.7% agreement with anti-PS/PT antibodies, suggests the presence of common but also specific PS/PT epitopes.

Conclusions: The increased thrombotic risk associated with the aPS/PT antibodies would justify their testing in all APS patients in complementarity with the conventional anti-phospholipid antibodies to propose the best-adjusted treatment.

Objectives: To investigate nailfold videocapillaroscopy (NVC) abnormalities in mixed connective tissue disease (MCTD).

Methods: Patients with MCTD followed at the Rheumatology Department in Cochin Hospital (Paris, France) were identified based on individual record review. Diagnosis of MCTD required fulfillment of one of the three sets of classification criteria. Clinical and laboratory data were collected and NVC was performed on 4 fingers of both hands by one assessor. NVC patterns were analysed by two independent observers.

Results: We identified 51 MCTD patients [mean age 51±12 years, 86% female, 31% had interstitial lung disease (ILD)]. NVC images were available for 40 patients. Three different NVC patterns were identified: 'normal' (15 %); 'non-specific microangiopathy' (40%) and 'scleroderma pattern' (45%). 'Scleroderma pattern' was associated with skin sclerosis (9/18 vs. 5/32; p=0.008) and digital ulcers (6/18 vs. 2/32; p=0.017). We observed a reduction in the number of capillaries in patients with ILD (4.80±1.87 vs. 6.03±1.47; p=0.039). Patients with severe reduction of capillary density (≤4/mm) were more likely to have ILD (5/7 vs. 5/33; p=0.002). Neoangiogenesis was more frequent in patients with ILD (6/13 vs. 4/27; p=0.034). The association between severe reduction of capillary density and ILD was observed independently of the presence of the 'scleroderma pattern' and skin sclerosis.

Conclusions: We identified three NVC patterns in MCTD patients. 'Scleroderma pattern' was associated with presence of skin sclerosis and digital ulcers. Severe capillary loss was significantly associated with the presence of ILD. Our results indicates that NVC may be helpful for disease risk stratification in MCTD.

Patients with systemic lupus erythematosus (SLE) are at increased risk of coronary heart disease (CHD). Even though the absolute risk of cardiovascular disease (CVD) among SLE patients increases with advancing age, younger female patients are at the greatest risk of developing acute myocardial infarction (AMI). These young patients are not considered to be at high risk for CVD using traditional risk assessment tools. Also, subclinical atherosclerosis is less common among young lupus patients. AMI could present with or without significant obstruction in coronary arteries in younger patients. There are no guidelines on appropriate cardiac screening of younger lupus patients, often without chest pain or who present with non-specific complaints. In recent years, the incidence of acute coronary syndrome (ACS) and ST-segment elevation AMI has decreased in the general population and in older lupus patients. Why has a similar decline in cardiovascular (CV) events not been seen in younger lupus patients? Since the issue of CVD in younger lupus patients is under-researched, a narrative review, rather than a systematic literature review was performed, based on the selected articles and points of view relevant to the topic. The aim of this review is to raise awareness of the relationship between SLE and CVD in younger ages, discuss possible non-atherosclerotic mechanisms of obstructive and non-obstructive CHD in lupus, elaborate on acute coronary syndromes unique for young patients, point out current challenges in identifiing at-risk patients for ACS, potential for new imaging techniques, the need for individualised treatment, with or without coronary stenting in ACS, and to underscore the relevance of CVD studies in young patients with SLE.

Objectives: Previous studies have reported the expansion of CD19+Siglec-10+ B cells in systemic lupus erythematosus (SLE) patients. However, the composition of this cell population, phenotype and characteristics are still unknown.

Methods: We examined this memory B-cell subset's composition and phenotype and determined the SYK and AKT phosphorylation levels by flow cytometry. Additionally, we explored the relationship between Siglec-10 expression on B-cell subsets and clinical manifestations.

Results: Our results indicated elevated levels of Siglec-10 on naive B cells in active SLE patients. Compared with healthy controls (HCs) and inactive SLE patients, the Siglec-10+ B cells in active SLE patients exhibited elevated CD40 and CD21low levels. The levels of Siglec-10 on naive B cells were positively correlated with the proportion of CD21low double negative (DN) B cells and the SLEDAI-2K score.

Conclusions: The results indicate that the upregulation of Siglec-10+/naive B cells may function as a feedback mechanism to regulate B cell hyperreactivity. Monitoring the proportion of Siglec-10+/naive B cells may contribute to the evaluation of disease progression in SLE.

Objectives: Inflammatory biomarkers such as C-reactive protein (CRP) lack discriminatory capacity to detect active disease in psoriatic arthritis (PsA). Our aim was to find CRP thresholds capable of discriminating active disease in both early and established PsA.

Methods: We included a total of 345 PsA patients (215 early-onset not exposed to high-impact therapies and 130 with established disease under biologics and oral targeted therapies). Discriminative CRP thresholds were determined by the Youden index, while their sensitivity/specificity balance was evaluated by the area under the receiver-operating characteristic (AUROC) curve.

Results: Cohort I (recent-onset PsA) included 215 consecutive patients, mean age 49.8 ± 13.9 years, 145 men (67.4%) and 70 women (32.6%). Cohort II (established PsA: mean duration 9.2 ± 7.1 years) included 130 consecutive patients, mean age 55.6 ± 11.2 years, 64 men (49.2%) and 66 women (50.8%). In cohort II, a CRP value around 0.20 mg/dl resulted discriminative for active disease (AUROC 0.71, OR 4.7, p<0.001). Among patients not exposed to anti-TNF drugs in cohort II, a CRP ≥0.22 mg/dl was highly discriminative for active disease (AUROC 0.86). In cohort I, no CRP values ​​ with good discriminative performance were obtained in any scenario. The standard inflammatory CRP value (≥0.5 mg/dl) did not provide discriminative advantage above the previous thresholds in either cohort.

Conclusions: Our results suggest the adoption of lower than standard CRP cut-off values ​​ for a better assessment of PsA in clinical practice. This seems to be more applicable in established than in recent-onset PsA.

Objectives: To clarify the impact of sarilumab (SAR) on the progression of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA).

Methods: We conducted a retrospective review of all consecutive RA patients from the KEIO-RA cohort who visited our institution between 2018 and 2024 and received SAR treatment. Patients were followed for 24 months from the initiation of SAR. The primary outcome was the rate of progression of ILD as assessed by high-resolution computed tomography (HRCT). We also conducted a literature review regarding the efficacy of SAR on RA-ILD in PubMed, Web of Science, and Scopus databases.

Results: Among 123 cases, 21 (17.1%) had ILD. The median age at SAR initiation was 56 years, and 71.4% were female. Except for 6 cases, SAR was administered as monotherapy via subcutaneous injection at 200 mg every two weeks. During SAR treatment, 18 cases (85.7%) exhibited stable HRCT findings, coupled with improvements in arthritis. Two cases with NSIP and OP patterns demonstrated improvements in both HRCT findings and arthritis post-SAR treatment. One case experienced an exacerbation of ILD at 18 months, with worsening arthritis observed prior to the deterioration of ILD. Serum KL-6 levels also improved or remained stable after SAR initiation, except in one case of ILD exacerbation. There were no adverse events, including serious infections, during the observation period. Additionally, our literature review identified a case of RA-ILD treated with SAR and achieved remission of arthritis and ILD.

Conclusions: In our study, SAR exhibited encouraging efficacy in stabilising RA-ILD in most cases.

This review comprehensively discusses the cross-reactivity of autoantibodies against modified proteins (AMPAs), the hallmark of rheumatoid arthritis (RA). We found that regardless of tissue sources, subtypes, or isotypes of B cells, AMPAs show high cross-reactivity within and across antigens undergoing citrullination, carbamylation, lysine-acetylation or ornithine-acetylation. The cross-reactive patterns of AMPAs display clonal and individual heterogeneity. Variations in the antibody reactivity to different modified antigens in RA are due to the diverse cumulative effects of cross-reactive profiles of AMPA clones. 'Shared motifs', as short motifs composed of one core modified residue with one or two flanking amino acids, are essential for AMPA cross-reactivity. AMPAs likely undergo affinity maturation towards shared motifs, during which their cross-reactivity to citrullinated antigens was increased, so collaterally was their cross-reactivity to other modifications due to structural similarities between modified residues. Cross-reactivity could aid the activation of AMPA B cells by facilitating T-cell signals from various modified antigens, direct pathogenic effects to tissues where modified antigens accumulate, and drive the clearance of in vivo modified antigens.