Objective. To test the hypothesis that T cell reactivity to self heat-shock protein 60 (Hsp60) in patients with remitting juvenile idiopathic arthritis (JIA) is part of an antiinflammatory, regulatory mechanism.Methods. Using peripheral blood-derived mononuclear cells (
Heterozygous mutations at amino acid position 577 of pyrin can induce an autosomal dominant autoinflammatory syndrome. This suggests that T577, located in front of the C-terminal B30.2/SPRY domain, is crucial for pyrin function.
Objective. To identify epitopes on Escherichia coli heat-shock protein (HSP) dnaJ or on homologous human HSP dnaJ involved in the induction/modulation of autoimmune inflammation in patients with oligoarticular juvenile idiopathic arthritis (JIA).Methods. We used a proliferation assay and cytokine production to evaluate the immune responses of Conclusion. This is the first description of a self-regulating immune modulator circuit active during autoimmune inflammation through recognition of HSP epitopes with different functional properties. These epitopes induce T cells with regulatory function. Such induction correlates with disease severity and prognosis.
These findings highlight a genetically distinct, sexually dimorphic feature of JIA with uveitis as compared to JIA without uveitis. The association could be indicative of the potential involvement of antigen presentation by HLA-DRβ1 in the development of uveitis in JIA. The results of this study may advance our progress toward improved treatments for, and possible prevention of, the sight-threatening complications of uveitis in children with JIA.
Introduction
In general SARS-CoV-2-infection during pregnancy is not considered to be an increased risk for severe maternal outcomes, but has been associated with an
increased risk for fetal distress. So far, there is no direct evidence of intrauterine vertical transmission and the mechanisms leading to the adverse outcomes are not well understood
Results
An asymptomatic pregnant woman with preterm fetal distress during the COVID19 pandemic was included. We obtained multiple maternal, placental and neonatal swabs, which showed a median viral load in maternal blood, urine, oropharynx, fornix posterior over a period of 6 days was 5.0 log copies /mL. The maternal side of the placenta had a viral load of 4.42 log copies /mL, while the fetal side had 7.15 log copies /mL. Maternal breast milk, feces and all neonatal samples tested negative. Serology of immunoglobulins against SARS-CoV-2 was tested positive in maternal blood, but negative in umbilical cord and neonatal blood. Pathological examination of the placenta included immunohistochemical investigation against SARS-CoV-2 antigen expression in combination with SARS-CoV-2 RNA in situ hybridization and transmission electron microscopy. It showed the presence of SARS-CoV-2 particles with generalized inflammation characterized by histiocytic intervillositis with diffuse perivillous fibrin depositions with damage to the syncytiotrophoblasts.
Discussion
Placental infection by SARS-CoV-2 lead to fibrin depositions hampering fetal-maternal gas exchange most likely resulted in fetal distress necessitating a premature emergency caesarean section. Postpartum, the neonate showed a clinical presentation resembling a pediatric inflammatory multisystem syndrome including coronary artery ectasia, most likely associated with SARS-CoV-2 (PIMS-TS) for which admittance and care on the Neonatal Intensive Care unit (NICU) was required, despite being negative for SARS-CoV-2. This highlights the need for awareness of adverse fetal and neonatal outcomes during the current COVID-19 pandemic, especially considering that the majority of pregnant women appear asymptomatic.
BackgroundResearch on Juvenile Idiopathic Arthritis (JIA) should support patients, caregivers/parents (carers) and clinicians to make important decisions in the consulting room and eventually to improve the lives of patients with JIA. Thus far these end-users of JIA-research have rarely been involved in the prioritisation of future research.Main bodyDutch organisations of patients, carers and clinicians will collaboratively develop a research agenda for JIA, following the James Lind Alliance (JLA) methodology. In a ‘Priority Setting Partnership’ (PSP), they will gradually establish a top 10 list of the most important unanswered research questions for JIA. In this process the input from clinicians, patients and their carers will be equally valued. Additionally, focus groups will be organised to involve young people with JIA. The involvement of all contributors will be monitored and evaluated. In this manner, the project will contribute to the growing body of literature on how to involve young people in agenda setting in a meaningful way.ConclusionA JIA research agenda established through the JLA method and thus co-created by patients, carers and clinicians will inform researchers and research funders about the most important research questions for JIA. This will lead to research that really matters.
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