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

B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial

INTRODUCTION: An over-expression of CD19 has been shown in B cells of systemic sclerosis (SSc) and B cells are thought to contribute to the induction of skin fibrosis in the tight skin mouse model. The aim was to define the outcome on safety and the change in skin score after rituximab therapy in SSc patients and to correlate the clinical characteristics with the levels of interleukin (IL)-6 and with the immune cell infiltrate detected by immunohistochemistry. METHODS: Nine patients with SSc with mean age 40.9 +/- 11.1 years were treated with anti-CD20, 1 g at time 0 and after 14 days. Skin biopsy was performed at baseline and during the follow-up. B-cell activating factor (BAFF) and IL-6 levels were also determined at the follow-up times. RESULTS: After 6 months patients presented a median decrease of the skin score of 43.3% (range 21.1-64.0%), and a decrease in disease activity index and disease severity index. IL-6 levels decreased permanently during the follow up. After treatment, a complete depletion of peripheral blood B cells was observed in all but 2 patients. Only 3 patients presented CD20 positive cells in the biopsy of the involved skin at baseline. CONCLUSIONS: Anti-CD20 treatment has been well tolerated and SSc patients experienced an improvement of the skin score and of clinical symptoms. The clear fall in IL-6 levels could contribute to the skin fibrosis improvement, while the presence of B cells in the skin seems to be irrelevant with respect to the outcome after B cell depletion

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

Climate risk index for Italy.

We describe a climate risk index that has been developed to inform national climate adaptation planning in Italy and that is further elaborated in this paper. The index supports national authorities in designing adaptation policies and plans, guides the initial problem formulation phase, and identifies administrative areas with higher propensity to being adversely affected by climate change. The index combines (i) climate change-amplified hazards; (ii) high-resolution indicators of exposure of chosen economic, social, natural and built- or manufactured capital (MC) assets and (iii) vulnerability, which comprises both present sensitivity to climate-induced hazards and adaptive capacity. We use standardized anomalies of selected extreme climate indices derived from high-resolution regional climate model simulations of the EURO-CORDEX initiative as proxies of climate change-altered weather and climate-related hazards. The exposure and sensitivity assessment is based on indicators of manufactured, natural, social and economic capital assets exposed to and adversely affected by climate-related hazards. The MC refers to material goods or fixed assets which support the production process (e.g. industrial machines and buildings); Natural Capital comprises natural resources and processes (renewable and non-renewable) producing goods and services for well-being; Social Capital (SC) addressed factors at the individual (people's health, knowledge, skills) and collective (institutional) level (e.g. families, communities, organizations and schools); and Economic Capital (EC) includes owned and traded goods and services. The results of the climate risk analysis are used to rank the subnational administrative and statistical units according to the climate risk challenges, and possibly for financial resource allocation for climate adaptation.This article is part of the theme issue 'Advances in risk assessment for climate change adaptation policy'

Low-dose Oral Imatinib in the treatment of systemic sclerosis interstitial lung disease unresponsive to cyclophosphamide. A phase II pilot study

none16noFraticelli P, Gabrielli B; Pomponio, G; Valentini, G; Bosello, S; Riboldi, P; Gerosa, M; Faggioli, P; Giacomelli, R; Del Papa, N; Gerli, R; Lunardi, C; Bombardieri, S; Malorni, W; Corvetta, A; Moroncini, G; Gabrielli, A.Fraticelli P, Gabrielli B; Pomponio, G; Valentini, G; Bosello, S; Riboldi, P; Gerosa, M; Faggioli, P; Giacomelli, R; Del Papa, N; Gerli, R; Lunardi, C; Bombardieri, S; Malorni, W; Corvetta, A; Moroncini, Gianluca; Gabrielli, Armand

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

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Quantitative and semi-quantitative computed tomography analysis of interstitial lung disease associated with systemic sclerosis: A longitudinal evaluation of pulmonary parenchyma and vessels

Objectives To evaluate interstitial lung disease associated with systemic sclerosis (SSc-ILD) and its changes during treatment by using quantitative analysis (QA) compared to semi-quantitative analysis (semiQA) of chest computed tomography (CT) scans. To assess the prognostic value of QA in predicting functional changes. Materials and methods We retrospectively selected 35 consecutive patients with SSc-ILD with complete pulmonary functional evaluation, Doppler-echocardiography, immunological tests, and chest CT scan at both baseline and follow-up after immunosuppressive therapy. CT images were analyzed by two chest radiologists for semiQA and by a computational platform for texture analysis of ILD patterns (CALIPER) for QA. Concordance between semiQA and QA was tested. Traction bronchiectasis severity was scored. Analysis of ROC curves was performed. Results Seventy CT scans were analyzed and QA failed in 4/70 scans. Thus, the final population included 31/35 patients (51.3\ub112.1 years). QA had a weak-to-good concordance with semiQA (ICC reticular:0.275; ICC ground-glass:0.667) and QA correlated better than semiQA (r = -0.3 to -0.74 vs r = -0.3 to -0.4) with functional parameters. Both methods correlated with traction bronchiectases score and pulmonary artery diameter at CT. A pulmonary artery diameter 29mm distinguished patients with lower lung volumes and ILD extent greater than 39% (p<0.001). Changes in QA patterns during treatment were not accurate (AUC: 0.50 to 0.70; p>0.05) in predicting disease progression as assessed by functional parameters, whereas variation in total lung volume at QA accurately predicted changes in the composite functional respiratory endpoint with FVC% and DLco% (AUC = 0.74; 95%CI: 0.54 to 0.93; p = 0.03). Conclusions Pulmonary QA of CT images can objectively quantify specific patterns of ILD changes during treatment in patients with SSc-ILD. Changes in QA patterns do not correlate with functional changes, but variation in total lung volume at QA accurately predicted changes in the composite functional respiratory endpoint with FVC% and DLco%. Pulmonary artery diameter at CT reflects the interstitial involvement, identifying patients with more severe prognosis