81 research outputs found
Ruolo della PKA/cAMP dipendente sulla regolazione dell'espressione di Foxp3 durante il differenziamento delle Treg in vitro
Le cellule T regolatorie sono una sottopopolazione di linfociti T che servono al mantenimento dell’omeostasi immunitaria attraverso il controllo della proliferazione delle cellule T convenzionali.
La proteina PKA che risente delle variazioni dei livelli di cAMP cellulari è parte della via PKA/cAMP dipendente ed è importante per la corretta esecuzione di molti processi cellulari.
E’ stata ampiamente dimostrata una relazione tra cAMP e l’immunimodulazione delle cellule T ed in particolare è stato dimostrato che il cAMP produce effetto inibitorio sulla proliferazione di tali cellule.
L’obiettivo di questo studio è stato quello di comprendere se la via di segnalazione PKA/cAMP dipendente avesse anche un ruolo sulla differenziazione delle Tconvenzionali in T regolatorie indotte in vitro
Clinical effectiveness of different natalizumab interval dosing schedules in a large Italian population of patients with multiple sclerosis
Introduction Natalizumab (NTZ) is one of the most
effective treatment options for multiple sclerosis (MS)
treatment. Our study aimed to evaluate the effectiveness
of NTZ when administered according to the extended
dosing strategy compared with standard 4-weekly
administration in a large Italian MS population.
Materials and methods This retrospective multicentre
study included patients with relapsing-remitting
MS
(RR-MS)
who received NTZ administrations between the
1 June 2012 and the 15 May 2018 and were followed
by the ’Italian MS Register’. All patients with MS were
stratified into two groups based on NTZ administration
schedule: standard interval dosing (SID) patients who
received infusions on average from 28 to 32 days
(median 30) and extended interval dosing (EID) including
patients who have been infused with interval between
33 and 49 days (median 43). Clinical data were assessed
at baseline (before starting NTZ), after 12 (T1) and 24
months (T2) of treatment.
Results Out of 5231 patients with RR-MS
screened,
2092 (mean age 43.2±12.0, 60.6% women) were
enrolled. A total of 1254 (59.9%) received NTZ
according to SID, and 838 (40.1%) according to EID. At
12 and 24 months, no differences in terms of annualised
relapse rate and disability status were found between the
two groups. Progression index and confirmed disability
worsening were similar between the two groups.
Discussion The use of NTZ with an extended interval
schedule showed similar effectiveness compared with
SID. Unchanged clinical efficacy of EID schedule may
raise the question of a possible advantage in terms of
tolerability and safety
Stimulation of beta2-adrenergic receptor increases CFTR function and decreases ATP levels in murine hematopoietic stem/progenitor cells
CD4+ T Cell Defects in a Mulibrey Patient With Specific TRIM37 Mutations
Mulibrey (muscle-liver-brain-eye) syndrome (MUL) is an autosomal recessive disorder
caused by mutations in the TRIpartite motif (TRIM)37 gene, encoding for TRIM37 a
member of the TRIM E3 ubiquitin ligase protein family. MUL patients are characterized
by growth retardation, dysmorphic features, and a wide range of abnormalities affecting
different organs. However, T-cell abnormalities have not been observed in MUL subjects,
to date. Here we described the immunological features of a MUL child carrying recently
identified TRIM37 mutations, a 17q22 deletion of maternal origin combined with a
TRIM37 variant of paternal origin. Here we found quantitative and functional defects in
CD4+ T cells fromthisMUL case. Low levels of TRIM37 protein were specifically detected
in CD4+ T cells ofMUL patient and associated with their altered proliferation and cytokine
production. Of note, both CD4+ and CD8+ T lymphocytes of MUL child displayed an
effector memory phenotype compared with healthy children. This clinical case research
highlighted the possible role of TRIM37 in the control of immune cell number and function,
especially in CD4+ T cells. Finally, this study may contribute to the novel mechanistic
studies aim of identifying, in depth, the role of the TRIM37 protein in the immune system
A new biological marker isolated and characterizated in sputum from lung pathology patients: microparticles
Risk of Getting COVID-19 in People With Multiple Sclerosis
Background and Objectives
Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in
people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies
(DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection
has not been evaluated so far. The objective of this study was to assess risk factors of contracting
SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR).
Methods
Acase-control (1:2) studywas set up. Cases included PwMSwith a confirmed diagnosis ofCOVID-19,
and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity
score–matched by the date of COVID-19 diagnosis, the date of last visit, and the region of
residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable
logistic regression models including demographic and clinical covariates. The impact of DMTs
was assessed in 3 independent logistic regression models including one of the following covariates: last
administeredDMT, previousDMTsequences, or the place where the last treatment was administered.
Results
A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without
COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly
associated (p < 0.02)with a higher risk of contractingCOVID-19. Patients receiving natalizumab as last
DMT(OR[95%CI]: 2.38 [1.66–3.42], p < 0.0001) and those who underwent an escalation treatment
strategy (1.57 [1.16–2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring
hospital access (1.65 [1.34–2.04], p < 0.0001) showed a significant higher risk than those taking self-administered DMTs at home.
Discussion
This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently
female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the
hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS.
Classification of Evidence
This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more
comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were
associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course
was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an
interferon beta agent was protective
Performance of current guidelines for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis
Publisher Copyright: Copyright © 2014 by the American College of Rheumatology.Results The study sample included 362 patients with systemic JIA and MAS, 404 patients with active systemic JIA without MAS, and 345 patients with systemic infection. The best capacity to differentiate MAS from systemic JIA without MAS was found when the preliminary MAS guidelines were applied. The 3/5-adapted HLH-2004 guidelines performed better than the 4/5-adapted guidelines in distinguishing MAS from active systemic JIA without MAS. The 3/5-adapted HLH-2004 guidelines and the preliminary MAS guidelines with the addition of ferritin levels ≥500 ng/ml discriminated best between MAS and systemic infections. Conclusion The preliminary MAS guidelines showed the strongest ability to identify MAS in systemic JIA. The addition of hyperferritinemia enhanced their capacity to differentiate MAS from systemic infections. The HLH-2004 guidelines are likely not appropriate for identification of MAS in children with systemic JIA. Objective To compare the capacity of the 2004 diagnostic guidelines for hemophagocytic lymphohistiocytosis (HLH-2004) with the capacity of the preliminary diagnostic guidelines for systemic juvenile idiopathic arthritis (JIA)-associated macrophage activation syndrome (MAS) to discriminate MAS complicating systemic JIA from 2 potentially confusable conditions, represented by active systemic JIA without MAS and systemic infection. Methods International pediatric rheumatologists and hemato-oncologists were asked to retrospectively collect clinical information from patients with systemic JIA-associated MAS and confusable conditions. The ability of the guidelines to differentiate MAS from the control diseases was evaluated by calculating the sensitivity and specificity of each set of guidelines and the kappa statistics for concordance with the physician's diagnosis. Owing to the fact that not all patients were assessed for hemophagocytosis on bone marrow aspirates and given the lack of data on natural killer cell activity and soluble CD25 levels, the HLH-2004 guidelines were adapted to enable the diagnosis of MAS when 3 of 5 of the remaining items (3/5-adapted) or 4 of 5 of the remaining items (4/5-adapted) were present.publishersversionPeer reviewe
Pro-inflammatory effect of cystic fibrosis sputum microparticles in the murine lung
BACKGROUND: The role of microparticles (MPs) in the inflammatory process of cystic fibrosis (CF) airways is not known. Here, we have studied the pro-inflammatory potential of CF MPs in a model of acute lung injury.
METHODS: Swiss mice were subjected to intratracheal administration of MPs obtained from CF and primary ciliary diskinesia (PCD) patients. Histopathology, total and differential cell counts in bronchoalveolar lavage fluid were used to evaluate the inflammatory reaction in the lung. Lipopolysaccharide (LPS)-like activity of MPs was studied by Limulus amebocyte lysate assay.
RESULTS: MPs obtained from acute CF patients determined peribronchial and perivascular inflammatory infiltrates similar to those elicited by LPS. This inflammation was granulocyte-dominated and higher than that determined by MPs obtained from stable CF, whereas PCD MPs caused a macrophage-dominated inflammation. While LPS-activity was not found in circulating blood MPs prepared from CF patients, it was present in MPs obtained from CF sputum and sputum CD66b(+) neutrophils. Finally, LPS-like activity was only detected in circulating MPs after incubation with LPS as well as in MPs obtained from LPS-stimulated neutrophils obtained from healthy donors.
CONCLUSIONS: These data suggest that the pro-inflammatory potential of neutrophil-derived MPs in the CF airways may be subsequent to the binding of shedded LPS
UCRAID (Ukrainian Citizen and refugee electronic support in Respiratory diseases, Allergy, Immunology and Dermatology) action plan.
Eight million Ukrainians have taken refuge in the European Union. Many have asthma and/or allergic rhinitis and/or urticaria, and around 100,000 may have a severe disease. Cultural and language barriers are a major obstacle to appropriate management. Two widely available mHealth apps, MASK-air® (Mobile Airways Sentinel NetworK) for the management of rhinitis and asthma and CRUSE® (Chronic Urticaria Self Evaluation) for patients with chronic spontaneous urticaria, were updated to include Ukrainian versions that make the documented information available to treating physicians in their own language. The Ukrainian patients fill in the questionnaires and daily symptom-medication scores for asthma, rhinitis (MASK-air) or urticaria (CRUSE) in Ukrainian. Then, following the GDPR, patients grant their physician access to the app by scanning a QR code displayed on the physician's computer enabling the physician to read the app contents in his/her own language. This service is available freely. It takes less than a minute to show patient data to the physician in the physician's web browser. UCRAID-developed by ARIA (Allergic Rhinitis and its Impact on Asthma) and UCARE (Urticaria Centers of Reference and Excellence)-is under the auspices of the Ukraine Ministry of Health as well as European (European Academy of Allergy and Clinical immunology, EAACI, European Respiratory Society, ERS, European Society of Dermatologic Research, ESDR) and national societies
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