Memory B cell subsets and plasmablasts are lower in early than in long-standing Rheumatoid Arthritis

Alterations of B cell subset distribution have been described in the peripheral blood (PB) of rheumatoid arthritis (RA) patients, but no data are available on differences between the onset and the established phases of the disease. The purpose of the study was to clarify whether a peculiar distribution of B cell subsets characterizes RA onset, thus leading to a more favorable clinical response to treatment, and to evaluate the possible association of a particular B cell subpopulation with response to therapy

Very early rheumatoid arthritis is the major predictor of major outcomes: clinical ACR remission and radiographic non-progression

OBJECTIVES: To identify predictors of clinical remission as well as of no x-ray progression in a cohort of early rheumatoid arthritis (ERA) treated with a tight-control protocol. METHODS: A total of 121 consecutive patients with ERA were treated to reach European League Against Rheumatism (EULAR) and/or American College of Rheumatology (ACR) clinical remission with methotrexate (MTX) for 3 months, then with a combination with anti-tumour necrosis factor if the patient did not achieve a 44-joint Disease Activity Score (DAS44) ≤2.4. At baseline and after 12 months all the patients had hand and foot joint radiographs. Very early rheumatoid arthritis (VERA) was defined as a disease with symptoms of less than 12 weeks. RESULTS: In all, 46.3% of the patients reached DAS remission and 24.8% achieved ACR remission. More than 60% of patients reached remission with MTX. Male sex and an erythrocyte sedimentation rate <35 mm/h at onset arose as significant predictors of EULAR remission, while VERA disease was the only predictor of ACR remission. At baseline, 28.1% of the patients were erosive. Multivariate analysis demonstrated that the only independent predictor of erosiveness was 'not having VERA disease'. After 12 months, VERA was the only factor predicting a lack of new erosions. CONCLUSIONS: VERA represents the best therapeutic opportunity in clinical practice to achieve a complete remission and to stop the erosive course of rheumatoid arthritis

PTPN22 1858C>T Polymorphism Distribution in Europe and Association with Rheumatoid Arthritis: Case-Control Study and Meta-Analysis

The PTPN22 rs2476601 polymorphism is associated with rheumatoid arthritis (RA); nonetheless, the association is weaker or absent in some southern European populations. The aim of the study was to evaluate the association between the PTPN22 rs2476601 polymorphism and RA in Italian subjects and to compare our results with those of other European countries, carrying out a meta-analysis of European data

Interstitial Lung Disease Associated With Autoimmune Rheumatic Diseases: Checklists for Clinical Practice

Background: Interstitial lung diseases (ILDs) are often associated with rheumatic diseases. Their early diagnosis and management are not only difficult, but also crucial, because they are associated with major morbidity and mortality and can be the first cause of death in autoimmune rheumatic diseases (ARDs). Objectives: By using methodologies, such as Nominal Group Technique (NGT) and Delphi Survey, the aims of this study were (1) to measure consensus between pulmonologists, radiologists, and rheumatologists experienced in the management of ARD-ILD; (2) to highlight the importance of a multidisciplinary approach; and (3) to provide clinicians with a practical tool aimed at improving the prompt recognition and follow-up of ILD associated with ARDs and of any possible rheumatic conditions underlying ILD. Results: During the NGT round, the Steering Committee defined 57 statements to be used in the Delphi survey. A total of 78 experts participated in the Delphi survey, namely 28 pulmonologists, 33 rheumatologists, and 17 radiologists. During this round, consensus on agreement was reached in 47 statements, while disagreement was not reached in any statements. A secondary questionnaire was drafted by the Steering Committee to obtain clearer indications on ILD-ARD \u201cred-flags\u201d and follow-up. Delphi Panelists took part also in the second-questionnaire survey. Answers from both surveys were used to draft two checklists of \u201cred flags\u201d sign or symptom suggestive of ILD and ARD, respectively, and two checklists on identification and monitoring of rheumatoid arthritis (RA) and systemic sclerosis (SSc) ILD. Limitations: This study is a consensus work, which cannot produce empiric data, and is limited to the Italian scenario. Conclusions: This work showed a high level of agreement, but also shows some divergent opinions between different experts. This underlines the importance of a multidisciplinary approach. Eventually, we believe the drafted checklists can help clinicians in the diagnosis and follow-up of ILD-ARD

Adult-onset Still's disease following COVID-19 vaccination

N/

An unusual lung involvement in scleroderma: lipoid pneumonia

No abstract availabl

Virtual reality telerehabilitation for postural instability in Parkinson's Disease: a multicenter, single-blind, randomized, controlled trial

Introduction: Telerehabilitation enables patients to access remote rehabilitation services for patient-physiotherapist videoconferencing in their own homes. Home-based virtual reality (VR) balance training has been shown to reduce postural instability in patients with Parkinson's disease (PD). The primary aim was to compare improvements in postural stability after remotely supervised in-home VR balance training and in-clinic sensory integration balance training (SIBT). Methods: In this multicenter study, 76 PD patients (modified Hoehn and Yahr stages 2.5-3) were randomly assigned to receive either in-home VR telerehabilitation (n = 38) or in-clinic SIBT (n = 38) in 21 sessions of 50 minutes each, 3 days/week for 7 consecutive weeks. VR telerehabilitation consisted of graded exergames using the Nintendo Wii Fit system; SIBT included exercises to improve postural stability. Patients were evaluated before treatment, after treatment, and at 1-month follow-up. Results: Analysis revealed significant between-group differences in improvement on the Berg Balance Scale for the VR telerehabilitation group (p = 0.04) and significant Time 7 Group interactions in the Dynamic Gait Index (p = 0.04) for the in-clinic group. Both groups showed differences in all outcome measures over time, except for fall frequency. Cost comparison yielded between-group differences in treatment and equipment costs. Conclusions: VR is a feasible alternative to in-clinic SIBT for reducing postural instability in PD patients having a caregiver

Covid-19 And Rheumatic Autoimmune Systemic Diseases: Role of Pre-Existing Lung Involvement and Ongoing Treatments

The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations

Scleroderma lung disease and \u3b2-thymosins:bronchoalveolar lavage fluid biomarkers

Obiettivi. Le \u3b2 timosine sono un gruppo di piccoli peptidi con una massa molecolare di 5 kDa. Queste chemochine sono coinvolte nella polimerizzazione intracellulare dell\u2019actina, ma possiedono anche numerose funzioni extracellulari e svolgono un ruolo nell\u2019angiogenesi e nell\u2019infiammazione. In particolare la timosina \u3b24 (T\u3b24) \ue8 un peptide ubiquitario essenzialmente intracellulare e strettamente coinvolto nella regolazione del citoscheletro inquanto \ue8 deputato a sequestrare l\u2019actina monomerica o a rilasciarla in caso di polimerizzazione. La T\u3b24 esercita, inotre, importanti funzioni regolatorie sia a livello intracellulare (i.e. signaling) sia a livello extracellulare (propriet\ue0 antinfiammatorie, propriet\ue0 favorenti la guarigione delle ulcere e l\u2019angiogenesi). Esiste una forma sulfossidata della T\u3b24, la sT\u3b24. La timosina \u3b210 (T\u3b210) \ue8 invece prodotta in corso di precancerosi, cancro ed infiammazione ed ha un\u2019azione antiangiogenetica ed \ue8 coinvolta nella modificazione della motilit\ue0 cellulare. Recentemente \ue8 stata descritta la presenza delle T\u3b2 nella saliva di soggetti sani e nel fluido crevicolare gengivale utilizzando la RP-HPLC-ESI-MS. L\u2019obiettivo di questo studio \ue8 stato quello di valutare l\u2019eventuale presenza delle T\u3b2 in un altro liquido biologico, il broncolavaggio alveolare (BAL) di soggetti sani e di soggetti affetti da sclerodermia con impegno polmonare. Inoltre, per individuare un marcatore di coinvolgimento polmonare in corso di sclerodermia sono stati studiati i livelli della T\u3b24, sT\u3b24 e della T\u3b210 e le loro reciproche variazioni in pazienti con e senza alveolite al BAL. Infine le concentrazioni delle T\u3b2 sono state correlate al coinvolgimento funzionale e radiologico del polmone. Dato il ruolo delle \u3b2 timosine nell\u2019angiogenesi e la loro capacit\ue0 di modulare il VEGF (vascular endothelial growth factor), anche i livelli di VEGF sono stati studiati nel BAL. Metodi. 15 controlli sani e 46 pazienti affetti da sclerodermia sono stati sottoposti a broncoscopia e i BAL ottenuti sono stati analizzati con un metodo proteomico. I pazienti affetti da sclerodermia sono inoltre stati sottoposti alle prove di funzionalit\ue0 respiratoria e alla TAC ad alta risoluzione del polmone al basale e dopo 12 mesi. Le T\u3b2 nel BAL sono state identificate mediante RP-HPLC-ESI-MS, mentre i livelli di VEGF sono stati valutati con metodica ELISA. Risultati. I livelli di T\u3b24 sono risultati significativamente pi\uf9 elevati nei pazienti affetti da sclerodermia (0.310 +/- 0.372 \ub5mol/L), rispetto ai controlli (0.112 +/- 0.084 \ub5mol/L), p=0.008. Considerando i pazienti affetti da sclerodermia i livelli di sT\u3b24 erano significativamente pi\uf9 elevati nei pazienti con alveolite (0.025 +/- 0.052 \ub5mol/L), rispetto ai pazienti senza alveolite (0.006 +/- 0.022 \ub5mol/L), p=0.05. Ventiquattro pazienti (52.2%) presentavano un\u2019alveolite al BAL. I pazienti che presentavano, dopo un anno di follow-up, un peggioramento dello score alveolare avevano livelli di T\u3b24 pi\uf9 bassi. I livelli di sT\u3b24 correlavano con la percentuale di neutrofili al BAL (r=+0.36, p=0.013). Sebbene i livelli di T\u3b210 fossero pi\uf9 elevati nei pazienti con sclerodermia rispetto ai controlli questa differenza non era statisticamente significativa. Inoltre vi era una correlazione indiretta tra i livelli di T\u3b210 e la DLCO nei pazienti con sclerodermia (r=-0.39, p=0.009). Sono stati inoltre evidenziati nel BAL livelli significativamente pi\uf9 bassi di VEGF nei pazienti sclerodermici rispetto ai controlli sani, ed in particolare nei pazienti con alveolite rispetto ai pazienti senza alveolite. Conclusioni. In questo studio per la prima volta sono stati studiati la presenza e i livelli di T\u3b2 (T\u3b24, sT\u3b24 e T\u3b210) nel BAL di soggetti sani e in pazienti sclerodermici con impegno polmonare. Mentre la T\u3b24 \ue8 costitutivamente espressa nel polmone, la sT\u3b24 e la T\u3b210 sono espresse solo in alcuni pazienti e in alcuni controlli sani. Gli elevati livelli di T\u3b24 nei pazienti sclerodermici rispetto ai controlli suggerisce la T\u3b24 come un possibile marcatore di patologia; mentre le diverse concentrazioni di sT\u3b24 nei pazienti con alveolite rispetto ai pazienti senza alveolite suggeriscono che questa molecola sia un possibile biomarcatore di stress ossidativo e di danno polmonare, vista anche la correlazione tra i livelli di sT\u3b24 e la percentuale di neutrofili. La correlazione tra i livelli di T\u3b210 e la DLCO, invece, suggerisce un possibile ruolo inibitorio della T\u3b210 sulla permeabilit\ue0 alveolo-capillare. Quindi questi risultati indicano un possibile coinvolgimento di questi piccoli fattori paracrini nella patogenesi della malattia sclerodermica e che la T\u3b24 possa avere un ruolo cito-protettivo nel danno tissutale del coinvolgimento polmonare sclerodermico. La presenza del prodotto di ossidazione della T\u3b24, la sT\u3b24, sembra invece rispecchiare la presenza di uno stato infiammatorio, caratteristico dell\u2019alveolite. I bassi livelli di VEGF nel BAL dei pazienti con alveolite sclerodermica confermano il possibile ruolo del VEGF nel mantenere l\u2019omeostasi alveolo-capillare del polmone e la correlazione inversa tra il VEGF e la sT\u3b24 \ue8 suggestivo del ruolo contrapposto delle due molecole nel processo alveolitico.Objective. The role of \u3b2-thymosins (T\u3b24, T\u3b24 sulfoxide [sT\u3b24], T\u3b210) in cytoscheleton rearrangement, angiogenesis, fibrosis and reparative process suggests a possible involvement of these peptides in the pathogenesis of systemic sclerosis (SSc). The aims of the study were to demonstrate the presence of T\u3b24, sT\u3b24 and T\u3b210 in bronchoalveolar lavage fluid (BALF) of SSc patients with interstitial lung disease (ILD) and to correlate their levels with the biologic, functional and radiological parameters of the lung involvement and to the progression of ILD. Considering the role of \u3b2-thymosins in the angiogenetic process and in modulation of vascular endothelial growth factor (VEGF) production, also the VEGF BAL levels were investigated. Patients and Methods. T\u3b24, sT\u3b24, T\u3b210 were determined by HPLC-ESI-MS in BALF samples of 46 SSc patients with ILD and of 15 control subjects. VEGF levels were evaluated by ELISA. Results. T\u3b24 levels were significantly higher in SSc patients than in controls (SSc: 0.310 +/- 0.372 \ub5mol/L vs controls: 0.112 +/- 0.084 \ub5mol/L, p=0.008). Nevertheless, lower BALF T\u3b24 levels were found in the SSc patients with significantly worsening in the alveolar score on HRCT after one-year follow-up. In SSc cohort, patients with alveolitis presented higher BAL levels of sT\u3b24 (0.025 +/- 0.052 \ub5mol/L) than SSc patient without alveolitis (0.006 +/- 0.022 \ub5mol/L), p=0.05. Higher sT\u3b24 BALF levels correlated with the smoking habits, the presence of alveolitis, the BALF neutrophil percentage count, an inverted BALF CD4/CD8 ratio, and a lower forced vital capacity. T\u3b210 levels directly correlated with the BALF lymphocyte percentage count and inversely with the carbon monoxide diffusing capacity. Furthermore SSc patients presented lower BAL VEGF levels compared to controls, principally the SSc patients with alveolitis. Conclusion. In this study for the first time the presence of T\u3b24, its sulfoxide form and T\u3b210 in human BALF has been described and the results suggested the possible involvement of these paracrine factors in the pathogenesis of scleroderma lung disease. As described in other studies, T\u3b24 seems to have a protective role against tissue damage even in SSc lung disease and its oxidation product sT\u3b24 seems to mirror the presence of an inflammatory condition. The correlation between T\u3b210 and DLCO suggests an inhibitory role of T\u3b210 in the alveolar capillary permeability, while the inverse correlation between VEGF levels and sT\u3b24 levels implies a opposite role of these two molecules