Serpin B1 defect and increased apoptosis of neutrophils in Cohen syndrome neutropenia

Duplomb, Laurence; Rivière, Julie; Jégo, Gaëtan; Costa, Romain Da; Hammann, Arlette; Racine, Jessica; Schmitt, Alain; Droin, Nathalie; Capron, Claude; Gougerot‐Pocidalo, Marie‐Anne; Dubrez, Laurence; Aral, Bernard; Lafon, Arnaud; Edery, Patrick; Ghoumid, Jamal; Blair, Edward; Chehadeh-Djebbar, Salima El; Carmignac, Virginie; Thévenon, Julien; Guy, Julien; Girodon, François; Bastie, Jean-Noël; Delva, Laurent; Faivre, Laurence; Thauvin‐Robinet, Christel; Solary, Éric

doi:10.1007/s00109-019-01754-4

Cited by 16 publications

(20 citation statements)

References 30 publications

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“…The data that support the findings of this study, including transcriptome data from 60 Grouping based on the six data-driven CoCena 2 sample groups G1-G6. the whole blood CoCena 2 network were identified and patients groups were assigned accordingly (G1-G6).…”

Section: Data Availabilitysupporting

confidence: 80%

Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

Aschenbrenner

Mouktaroudi²,

Krämer

et al. 2020

Preprint

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The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases calls for a better characterization and understanding of the changes in the immune system. Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 11 COVID-19 patients. Comparison of COVID-19 blood transcriptomes with those of a collection of over 2,600 samples derived from 11 different viral infections, inflammatory diseases and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host.

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Section: Data Availabilitysupporting

confidence: 80%

Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

Aschenbrenner

Mouktaroudi²,

Krämer

et al. 2020

Preprint

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“…The CS diagnosis was confirmed in the study by the presence of mutations in the VPS13B gene 11 . The size of our cohort was close to those retrieved by other authors 3,8 .…”

Section: Discussionsupporting

confidence: 85%

“…Patients’ inclusion process occurred from July 2013 until June 2014 in Dijon University Hospital, France. The CS diagnosis was genetically confirmed in the study by the presence of mutations in the VPS13B gene 11 . For this ancillary study, CS patients underwent an oral examination.…”

Section: Methodsmentioning

confidence: 92%

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Periodontal disorders in a cohort of patients with Cohen syndrome

Lafon

Faivre

Seux

et al. 2020

Special Care in Dentistry

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AimsCohen syndrome (CS) is an uncommon autosomal recessive disorder due to mutations in vacuolar protein sorting 13B, with an intermittent presence of neutropenia. Contrary to other clinical phenotypic features, oral health has been little investigated in CS. We described oral health and dental hygiene in a cohort of CS patients.Methods and ResultsTwelve CS patients with neutropenia (<1500/mm3) were recruited in the dental department of Dijon University Hospital (France). Patients underwent oral examination, and blood samples were collected. Oral health markers were described and compared between patients with moderate and severe neutropenia (<500/mm3). In 12 patients (mean age = 21.1 years, SD = 13.7, six females), 45.5% brushed at least twice daily their teeth, and the same percentage annually visited a dentist. Dental plaque index was high (mean = 1.7, SD = 1.4). So was the number of lost teeth per patient, notably among adults (mean = 13.8, SD = 9.8). Elevated markers of periodontitis were noted as percentage of bleeding dental sites (mean = 70.2%, SD = 45.2%) or Gingival Index (mean = 2.2, SD = 1.0). The severity of neutropenia was correlated to the level of tooth‐loss (P = .03).ConclusionThis study highlighted in CS patients worrisome oral health and dental follow‐up in the context of intellectual disability with behavioural anomalies. More attention is needed by care‐givers on oral condition in CS.

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“…Neutropenia in Cohen syndrome occurs from an exaggerated rate of neutrophil apoptosis and is most commonly managed with G-CSF [ 4 , 5 ]. Our patient had been treated with G-CSF from the age of 13 and previous attempts to wean this had failed secondary to recurrence of severe aphthous ulcers, which affected his quality of life.…”

Section: Case Presentationmentioning

confidence: 99%

Variceal Bleed and Portal Hypertensive Gastropathy in a Noncirrhotic Patient with Isolated Splenomegaly

Hasan

Dmitriew

Leonard

2020

Case Reports in Hepatology

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Portal hypertension caused by cirrhosis is the most common etiology of esophageal varices. However, abnormalities of the splenoportal axis in the absence of liver disease may also cause portal hypertension resulting in varices. We report a rare case of esophageal variceal bleed in a noncirrhotic patient with isolated splenomegaly secondary to chronic granulocyte colony stimulating factor (G-CSF) therapy. The patient is a 26-year-old male with Cohen syndrome who required long-term G-CSF treatment for chronic neutropenia. He presented with large volume hematemesis and pancytopenia in the setting of known splenomegaly with no evidence of cirrhosis. An urgent EGD revealed active variceal bleeding and portal hypertensive gastropathy. The patient was appropriately resuscitated and underwent a successful transjugular intrahepatic portosystemic shunt and CT-guided coil placement for the bleeding varices. We are the first to report variceal bleed as a complication of long-term G-CSF use, a life-threatening consequence that requires urgent intervention.

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Serpin B1 defect and increased apoptosis of neutrophils in Cohen syndrome neutropenia

Cited by 16 publications

References 30 publications

Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients

Periodontal disorders in a cohort of patients with Cohen syndrome

Variceal Bleed and Portal Hypertensive Gastropathy in a Noncirrhotic Patient with Isolated Splenomegaly

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