Disappearance of slan-positive non-classical monocytes for diagnosis of chronic myelomonocytic leukemia with an associated inflammatory state

International audienceNo abstract availabl

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

La numération des érythroblastes circulants, étude comparative de 133 échantillons par trois méthodes (automate compte-globules, cytométrie en flux, microscopie optique)

PARIS-BIUP (751062107) / SudocSudocFranceF

Automated Detection of Dysplasia: Data Mining from Our Hematology Analyzers

International audienceMyelodysplastic syndromes (MDSs) are clonal hematopoietic diseases of the elderly, charac-terized by chronic cytopenia, ineffective and dysplastic hematopoiesis, recurrent genetic abnormalities and increased risk of progression to acute myeloid leukemia. Diagnosis on a complete blood count (CBC) can be challenging due to numerous other non-neoplastic causes of cytopenias. New genera-tions of hematology analyzers provide cell population data (CPD) that can be exploited to reliably detect MDSs from a routine CBC. In this review, we first describe the different technologies used to obtain CPD. We then give an overview of the currently available data regarding the performance of CPD for each lineage in the diagnostic workup of MDSs. Adequate exploitation of CPD can yield very strong diagnostic performances allowing for faster diagnosis and reduction of time-consuming slide reviews in the hematology laboratory

Reference Values for WBC Differential by Hematoflow Analysis

International audienceObjectives - WBC differentials performed using flow cytometry with monoclonal antibodies have been developed in the last decade and are nowadays integrated into the routine workflow of some laboratories. Definition of reference values for each population is required in order to achieve an automatic validation of the results by laboratory software. Methods - We analyzed 584 samples from three hospitals using the Hematoflow solution to define the reference values. Results - Reference values are presented for five groups according to age (0-5, 6-11, 12-19, 20-69, and >69 years). Conclusions - These normal values will be helpful in the definition of relevant threshold for the automatic validation of samples analyzed by flow cytometry and the flagging of pathologic samples

High sensitivity of the Hematoflow™ solution for chronic myelomonocytic leukemia screening

International audienceBackground: Accumulation of classical monocytes CD14++CD16– (also called MO1) ≥ 94% can accurately distinguish chronic myelomonocytic leukemia (CMML) from reactive monocytosis. The HematoFlow™ solution, able to quantify CD16 negative monocytes, could be a useful tool to manage monocytosis which remains a common issue in routine laboratories.Methods: Classical monocytes were quantified from 153 whole blood samples collected on EDTA using both flow cytometry methods, either MO1 percentage determination by the multiparameter assay previously published and regarded here as the reference method, or CD16 negative monocyte percentage determination by the means of HematoFlow™.Results: Both methods of classical monocyte percentage determination were highly and significantly correlated (r = 0.87, P < 0.0001). The HematoFlow™ solution leant toward an overestimation of the genuine classical monocyte percentages obtained by the reference method. Percentages of CD16 negative monocytes provided by HematoFlow were higher than 94% for all the 73 patients displaying classical monocytes MO1 found ≥94% by the reference method, indicating a sensitivity of 100%. Furthermore, the calculation of CD16 negative monocyte percentage can be easily computerized and integrated to the middleware.Conclusions: We propose a new application of the Hematoflow™ solution that can be used as a flag system for monocytosis management and CMML detection

<i>TET2</i> mutational status affects myelodysplastic syndrome evolution to chronic myelomonocytic leukemia

International audienc

Lower respiratory tract involvement in recurrent respiratory papillomatosis in a multicentric cohort study

International audienceRecurrent respiratory papillomatosis (RRP) is a rare disease due to chronic Human Papillomavirus infection, occurring in childhood (JoRRP) or adults (AoRRP). PRR characterized by progressive obstruction papillomas mostly affecting upper airway and more rarely lower tract (LRT), including lungs. This study describes the characteristics of Jo AoRRP LRT at adulthood. French Quebecers’ national retrospective clinical, histological, therapeutic prognostic with RRP-LRT. Among 67 patients (pts), 17 (25%) were JoRRP 50 (75%) AoRRP. The mean age diagnosis was 5 yrs for 54 ENT involvement observed all 23 (46%) Lung 11 (76%) 2 (4%) Mean latency duration between lung 26 4 CT-scan findings cysts pts (74%) nodules/mass (13%), predominating lobes. 13 (19%) had malignant transformation squamous cell carcinoma trachea (n=3) (n=10). Associated factors female gender, JoRRP, HPV-11, repeated desobstruction tracheostomy while they HPV-16 presence involvements transformation. Overall mortality 9%, form, being (pandl