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Abstract: We analyzed peripheral blood (PB) and synovial fluid (SF) mononuclear cells from 16 rheumatoid arthritis (RA), 9 spondyloarthritis (SpA), 3 microcrystal arthritis patients, to define the presence of Th17 and Th1 and their relationship with inflammatory activity, and TCR-zeta chain and ZAP-70 levels. Th17 were significantly higher in SF than in PB and more abundant in microcrystal arthritis patients compared to the other groups. Irrespectively of the diagnosis, SF Th17 percentages correlated with joint (SF total leukocyte count, neutrophil percentage) and systemic (C reactive protein [CRP], fibrinogen, erythrocyte sedimentation rate) inflammation markers. SF Th1 percentages directly correlated with inflammation and disease activity (CRP, swollen joint count [SJC]) indices in SpA, but not in RA patients. These observations support the role of Th17 in the pathogenesis of inflammatory arthritides. The TCR-zetadim lymphocytes in SF were found to produce the highest amounts of cytokines including IL-17, whereas no ZAP-70 impairment was associated to Th17. [ABSTRACT FROM AUTHOR]

Abstract: B cells have acquired an important role in the pathogenesis of rheumatoid arthritis (RA) since B cell depletion allowed to rescue patients poorly responders to TNFα blockers. This study focused on the involvement of ZAP-70 as a bio-marker of B cells immune activation in RA. ZAP-70 expression in synovial fluid (SF) B cells obtained from RA patients was increased compared to SF B cells of osteoarthritis (OA) patients. Moreover we found that ZAP-70 positive/CD38 positive and ZAP-70 positive/CD5 positive B cells were enriched in SF. The analysis of B cell apoptosis in vitro showed that the percentage of ZAP-70 negative B cells spontaneously undergoing apoptosis was significantly higher than ZAP-70 positive B cells. The ZAP-70 positive B cell ratio (SF/peripheral blood (PB)) showed a positive correlation with SF autoantibody levels and with local levels of BAFF and IL6. ZAP-70 positive B cells seem to define a subset characterized by increased survival and high relationship with local inflammation and autoimmunity. [Copyright &y& Elsevier]

Intravenous iloprost is currently recommended in the treatment of Raynaud's phenomenon (RP) refractory to oral therapy and of digital ulcers (DUs) related to systemic sclerosis (SSc). In real-life practice there is a huge heterogeneity about the Iloprost regimens used. A survey was carried out on SSc patients that interrupted Iloprost infusion to compare acral vascular symptoms just before Iloprost withdrawal and just after the missed infusion. Severity, and frequency of RP, new DUs onset or aggravation of those pre-existing were reported. Last available capillaroscopic images were also evaluated. The analysis includes 50 patients. After iloprost withdrawal, 11 patients reported a RP worsening because of enhanced intensity (p = 0.007). Only 8 patients of them also complained of an increased frequency (p = 0.07). None of the patients experienced digital ulcers for the first-time during quarantine. Among the 27 patients with a history of digital ulcers, 9 reported worsening and 7 recurrence of DUs. Overall, 17 patients (34.0 %) complained of a worsening of SSc vascular acral manifestations, namely RP or DUs. Reduced capillary density was associated with RP worsening, in particular, each unit increase of capillary density corresponds to an average 44 % decrease in the odds of RP worsening (OR 0.56, CI 95 % 0.36–0.97, p = 0.037). As for RP worsening, the aggravation of DU was associated with a lower capillary density. Low capillary density can predict a worsening of both RP and DUs in controlled quarantine conditions within a month after iloprost discontinuation in SSc patients. • Coronavirus pandemic provided unrepeatable circumstances close to an experimental condition to assesses the effect of iloprost withdrawal in scleroderma. • Low capillary density at capillaroscopy can predict an early worsening of both Raynaud's phenomenon and digital ulcers after iloprost discontinuation. • Capillaroscopy could be used to personalize Iloprost regimens in scleroderma patients. [ABSTRACT FROM AUTHOR]

Increasing evidence points to endothelial dysfunction as a key pathophysiological factor in coronavirus disease-2019 (COVID-19). No specific methods have been identified to predict, detect and quantify the microvascular alterations during COVID-19. Our aim was to assess microvasculature through nailfold videocapillaroscopy (NVC) in COVID-19 patients. We performed NVC in patients with a confirmed diagnosis of COVID-19 pneumonia. Elementary alterations were reported for each finger according to a semi-quantitative score. Capillary density, number of enlarged and giant capillaries, number of micro-hemorrhages and micro-thrombosis (NEMO score) were registered. We enrolled 82 patients (mean age 58.8 ± 13.2 years, male 68.3%) of whom 28 during the hospitalization and 54 after recovery and hospital discharge. At NVC examination we found abnormalities classifiable as non-specific pattern in 53 patients (64.6%). Common abnormalities were pericapillary edema (80.5%), enlarged capillaries (61.0%), sludge flow (53.7%), meandering capillaries and reduced capillary density (50.0%). No pictures suggestive of scleroderma pattern have been observed. Acute COVID-19 patients, compared to recovered patients, showed a higher prevalence of hemosiderin deposits as a result of micro-hemorrhages (P =.027) and micro-thrombosis (P <.016), sludge flow (P =.001), and pericapillary edema (P <.001), while recovered patients showed a higher prevalence of enlarged capillaries (P <.001), loss of capillaries (P =.002), meandering capillaries (P <.001), and empty dermal papillae (P =.006). COVID-19 patients present microvascular abnormalities at NVC. Currently ill and recovered subjects are characterized by a different distribution of elementary capillaroscopic alterations, resembling acute and post-acute microvascular damage. Further studies are needed to assess the clinical relevance of NVC in COVID-19. • We assessed and accurately described peripheral microvasculature in COVID-19 patients through nailfold videocapillaroscopy. • Capillary alterations at the nailfold bed suggest a broad COVID-related microvascular involvement. • Different alterations in acutely-ill and recovered patients resemble a transition from acute to post-acute injury. [ABSTRACT FROM AUTHOR]