In systemic lupus erythematosus (SLE), autoantibody production can lead to kidney damage and failure, known as lupus nephritis. Basophils amplify the synthesis of autoantibodies by accumulating in ...secondary lymphoid organs. Here, we show a role for prostaglandin D2 (PGD2) in the pathophysiology of SLE. Patients with SLE have increased expression of PGD2 receptors (PTGDR) on blood basophils and increased concentration of PGD2 metabolites in plasma. Through an autocrine mechanism dependent on both PTGDRs, PGD2 induces the externalization of CXCR4 on basophils, both in humans and mice, driving accumulation in secondary lymphoid organs. Although PGD2 can accelerate basophil-dependent disease, antagonizing PTGDRs in mice reduces lupus-like disease in spontaneous and induced mouse models. Our study identifies the PGD2/PTGDR axis as a ready-to-use therapeutic modality in SLE.
Abstract JC virus (JCV) infection of glial cells can lead to progressive multifocal leukoencephalopathy (PML) in immunocompromised patients. A newly described phenotype of the infection is infection ...of neurons. This distinct clinical and radiological syndrome is named JCV granule cell neuronopathy, characterized by exclusive or predominant cerebellar atrophy. We report the clinical and radiological longitudinal findings of 5 HIV-infected patients referred to us between September 2004 and November 2011 who exhibited JCV granule cell neuronopathy (4 probable cases and 1 possible). The association of immunocompromised status, progressive cerebellar syndrome, MRI abnormalities with cortical cerebellar atrophy and cerebrospinal fluid positive for JCV on PCR allowed for a highly probable diagnosis. The reversal of the immunocompromised status is the only way to stop the disease evolution. Motor functioning can remain impaired, but the illness itself, unlike progressive multifocal leukoencephalopathy, does not seem to threaten life.
In systemic lupus erythematosus (SLE), autoantibody production can lead to kidney damage and failure, known as lupus nephritis. Basophils amplify the synthesis of autoantibodies by accumulating in ...secondary lymphoid organs. Here, we show a role for prostaglandin D
(PGD
) in the pathophysiology of SLE. Patients with SLE have increased expression of PGD
receptors (PTGDR) on blood basophils and increased concentration of PGD
metabolites in plasma. Through an autocrine mechanism dependent on both PTGDRs, PGD
induces the externalization of CXCR4 on basophils, both in humans and mice, driving accumulation in secondary lymphoid organs. Although PGD
can accelerate basophil-dependent disease, antagonizing PTGDRs in mice reduces lupus-like disease in spontaneous and induced mouse models. Our study identifies the PGD
/PTGDR axis as a ready-to-use therapeutic modality in SLE.
We aimed to evaluate the prognostic value of FDG pericardial uptake using FDG-PET/CT in patients admitted for acute pericarditis with pericardial effusion.
In this monocentric retrospective cohort ...study, all patients admitted for idiopathic acute pericarditis with pericardial effusion from January 2009 to December 2016 who underwent a FDG-PET/CT at diagnosis were considered. Pericardial FDG uptake was measured by generating a volume of interest to calculate the maximal standardized uptake value. The primary outcome was the pericarditis relapse rate during follow-up.
FDG-PET/CT was performed 23 7–99 days after diagnosis in 39 patients (52 18–83 years, 43.6% of women) admitted for acute pericarditis with pericardial effusion. During a median follow-up period of 7.6 2.4–77.2 months, 7 (17.9%) patients suffered pericarditis relapse that occurred 3.8 1.6–14.6 months after FDG-PET CT. In the multivariable analysis, pericardial FDG uptake at diagnosis (OR: 16.6; 95% confidence interval CI: 1.25 to 220.8; p = 0.033) was independently associated with pericarditis relapse. Eventually, patients with pericardial FDG uptake at diagnosis had a higher recurrence rate during follow up (p = 0.047).
In acute pericarditis with pericardial effusion, increased FDG-PET/CT pericardial uptake is associated with a higher risk for relapse.
•Pericarditis relapse is a major complication of acute pericarditis•Relapsing pericarditis is ascribed to an auto-inflammatory process•FDG-PET CT is the mainstay diagnostic test for nuclear imaging of cardiac inflammation•FDG-PET CT pericardial uptake identifies patients at risk for pericarditis relapse
Le virus JC peut entraîner une atrophie cérébelleuse rapide par infection des neurones de la couche des grains du cervelet, parfois sans lésion de leuco-encéphalite multifocale progressive (LEMP) ...associée.
Nous rapportons 5 cas de granulopathie cérébelleuse due au JC virus (GC-JC) survenus au cours d’une infection par le VIH.
Cinq dossiers de patients examinés dans le service de neurologie de l’hôpital de St-Denis de 2004 à 2011 ont été analysés rétrospectivement. Le diagnostic de GC-JC a été retenu sur les critères suivants : atteinte clinico-radiologique exclusive de la fosse postérieure, absence d’autre cause, présence d’ADN du virus JC dans le LCR par PCR (GC-JC définie) ou pas (GC-JC clinique présumée).
Les cinq patients étaient tous profondément immunodéprimés (entre 20 et 100 CD4/mm3). L’IRM initiale était normale ou montrait une atrophie isolée progressive du cervelet. La recherche d’ADN du virus JC dans le LCR était positive dans 4 cas. Les IRM successives montraient une atrophie majeure du cervelet puis un hypersignal plus ou moins marqué du cervelet, du pont, des pédoncules cérébelleux moyens et souvent un aspect de croix pontique.
La littérature montre que l’infection de la fosse postérieure par le JC virus existe, soit dans le cadre d’une LEMP classique, supra et/ou infra-tentorielle, soit plus rarement sans atteinte de la substance blanche. L’infection des neurones de la couche des grains du cervelet est en fait fréquente chez l’immunodéprimé, et responsable en cas d’infection active d’une perte neuronale.
Une atrophie rapide et isolée du cervelet chez un patient immunodéprimé doit faire évoquer une granulopathie cérébelleuse liée au JC virus. Le diagnostic repose sur l’IRM et la mise en évidence du virus JC dans le LCR.
Acute meningitis can be the first manifestation of an underlying systemic inflammatory disorder (SID). In the current study, we aimed to identify clinical indicators for SIDs in patients admitted for ...acute aseptic meningitis. All patients hospitalised for acute aseptic meningitis over a 4-year period in a department of internal medicine were included retrospectively. Patients with neoplastic meningitis were excluded. Extraneurological signs were recorded using a systematic panel. Systemic inflammatory disorder diagnosis was made according to current international criteria. Forty-three (average age 46 years range 19–82 years, 60% females) consecutive patients were analysed retrospectively. Of these, 23 patients had an SID (mostly sarcoidosis and Behçet’s disease). Multiple logistic regression analysis showed that the probability of an SID was 93.7% in patients with both neurological and extraneurological signs, but 14.9% in patients with neither neurological nor extraneurological signs. In conclusion, clinical sorting according to both neurological and extraneurological signs could help to identify patients with acute aseptic meningitis caused by an SID.
Like pneumonia, coronavirus disease 2019 (COVID-19) is characterized by a massive infiltration of innate immune cells (such as polymorphonuclear leukocytes) into the airways and alveolar spaces. ...These cells release proteases that may degrade therapeutic antibodies and thus limit their effectiveness. Here, we investigated the in vitro and ex vivo impact on anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) IgG1s and other IgG subclasses (IgG2 and IgG4) of the neutrophil elastase, proteinase 3 and cathepsin G (the three main neutrophil serine proteases) found in endotracheal aspirates from patients with severe COVID-19. Although the IgGs were sensitive to neutrophil serine proteases, IgG2 was most resistant to proteolytic degradation. The two anti-SARS CoV2 antibodies (casirivimab and imdevimab) were sensitive to the lung's proteolytic environment, although neutrophil serine protease inhibitors only partly limited the degradation. Overall, our results show that the pneumonia-associated imbalance between proteases and their inhibitors in the airways contributes to degradation of antiviral antibodies.
Legionnaires disease (LD) is a rare, life-threatening opportunistic bacterial infection that poses a significant risk to patients with impaired cell-mediated immunity such as solid organ transplant ...recipients. However, the epidemiologic features, clinical presentation, and outcomes of LD in this population are poorly described.
What are the clinical manifestations, radiologic presentation, risk factors for severity, treatment, and outcome of LD in solid organ transplant recipients?
In this 10-year multicenter retrospective cohort study in France, where LD notification is mandatory, patients were identified by hospital discharge databases. Diagnosis of LD relied on positive culture findings from any respiratory sample, positive urinary antigen test (UAT) results, positive specific serologic findings, or a combination thereof. Severe LD was defined as admission to the ICU.
One hundred one patients from 51 transplantation centers were eligible; 64 patients (63.4%) were kidney transplant recipients. Median time between transplantation and LD was 5.6 years (interquartile range, 1.5-12 years). UAT results were positive in 92% of patients (89/97). Among 31 patients with positive culture findings in respiratory samples, Legionella pneumophila serogroup 1 was identified in 90%. Chest CT imaging showed alveolar consolidation in 98% of patients (54 of 57), ground-glass opacity in 63% of patients (36 of 57), macronodules in 21% of patients (12 of 57), and cavitation in 8.8% of patients (5 of 57). Fifty-seven patients (56%) were hospitalized in the ICU. In multivariate analysis, severe LD was associated with negative UAT findings at presentation (P = .047), lymphopenia (P = .014), respiratory symptoms (P = .010), and pleural effusion (P = .039). The 30-day and 12-month mortality rates were 8% (8 of 101) and 20% (19 of 97), respectively. In multivariate analysis, diabetes mellitus was the only factor associated with 12-month mortality (hazard ratio, 3.2; 95% OR, 1.19-8.64; P = .022).
LD is a late and severe complication occurring in solid organ transplant recipients that may present as pulmonary nodules on which diabetes impacts its long-term prognosis.
Legionnaires disease (LD) is a rare, life-threatening opportunistic bacterial infection that poses a significant risk to patients with impaired cell-mediated immunity such as solid organ transplant ...recipients. However, the epidemiologic features, clinical presentation, and outcomes of LD in this population are poorly described.
What are the clinical manifestations, radiologic presentation, risk factors for severity, treatment, and outcome of LD in solid organ transplant recipients?
In this 10-year multicenter retrospective cohort study in France, where LD notification is mandatory, patients were identified by hospital discharge databases. Diagnosis of LD relied on positive culture findings from any respiratory sample, positive urinary antigen test (UAT) results, positive specific serologic findings, or a combination thereof. Severe LD was defined as admission to the ICU.
One hundred one patients from 51 transplantation centers were eligible; 64 patients (63.4%) were kidney transplant recipients. Median time between transplantation and LD was 5.6 years (interquartile range, 1.5-12 years). UAT results were positive in 92% of patients (89/97). Among 31 patients with positive culture findings in respiratory samples, Legionella pneumophila serogroup 1 was identified in 90%. Chest CT imaging showed alveolar consolidation in 98% of patients (54 of 57), ground-glass opacity in 63% of patients (36 of 57), macronodules in 21% of patients (12 of 57), and cavitation in 8.8% of patients (5 of 57). Fifty-seven patients (56%) were hospitalized in the ICU. In multivariate analysis, severe LD was associated with negative UAT findings at presentation (P = .047), lymphopenia (P = .014), respiratory symptoms (P = .010), and pleural effusion (P = .039). The 30-day and 12-month mortality rates were 8% (8 of 101) and 20% (19 of 97), respectively. In multivariate analysis, diabetes mellitus was the only factor associated with 12-month mortality (hazard ratio, 3.2; 95% OR, 1.19-8.64; P = .022).
LD is a late and severe complication occurring in solid organ transplant recipients that may present as pulmonary nodules on which diabetes impacts its long-term prognosis.
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