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Objectives Elevated free T3 (FT3) is an important feature for the early diagnosis of several diseases among which Grave’s disease or Allan-Hernon-Dudley syndrome. However, there is a lack of age-adapted reference intervals for plasma thyroid hormones in children. We conducted a study to define reference values of peripheral FT3 in children using a commonly used automated immunoassay. Methods All thyroid function test (TFT) results from our lab collected during 9 months were extracted anonymously, and reference intervals establishment followed recommendations validated by International Federation of Clinical Chemistry (IFCC). Results We defined five reference intervals covering the whole pediatric period. Overall, 26.1% of peripheral FT3 measured in children with normal TSH are out of the adult reference range, and 22.2% are upper it leading to misinterpretation. In a 9-month old patient with severe neurodevelopmental disorders, a pathological elevated FT3 has been securely interpreted using the newly established interval. Conclusions The study highlights the poor relevance of adult intervals in pediatric cares, as it confirms that plasmatic FT3 is higher during the whole pediatric period. This work reports useful age-adapted reference intervals for free T3 in pediatrics using a widely used electrochemiluminescent Immunoassay (ECLIA) kit.

The negatively charged nitrogen-vacancy centre (so-called NV-centre) in diamond is one of the most promising systems for applications in quantum technologies because of the possibility to optically manipulate and read out the spin state of this defect, even at room temperature. Nevertheless, obtaining high NV densities (>500 ppb) close to the surface (5–20nm) while maintaining good spin properties remain challenging. In this work we rely on a versatile ion implantation system allowing both implanting nitrogen using N2+and creating vacancies with He+ion bombardment at variable energies and fluence to create shallow NV ensembles. By optimizing the ion irradiation conditions as well as the surface preparation prior to treatment we successfully increase the amount of created colour centres while demonstrating narrow magnetic resonance linewidths. This paper has been published byIOP under the reference:Midrel Wilfried Ngandeu Ngambouet al2022Mater. Quantum. Technol.2045001 .

Assay of sex hormone binding globulin (SHBG), the main carrier protein for sexual steroids, is prescribed mainly by endocrinologists and performed in specialized laboratories. This study aimed to evaluate the analytic performance of an automated immunochemiluminescent assay (ImmunoDiagnostic Systems (IDS), Boldon, United Kingdom) compared to a manual radioimmunoassay (Cisbio Bioassays, Codolet, France). It further aimed to assess the suitability of the reference values proposed by IDS.One hundred and forty sera were used to assess the analytic performance of the IDS kit. The coefficients of variation (CV%) for within- and between-run precision were calculated. The reference values provided by IDS were recalculated based on the regression curve equation obtained by comparing the IDS and Cisbio values on Passing-Bablok regression. The new sex-based reference values were then established and their concordance with clinical status was evaluated on Kappa coefficient.The new kit correlated strongly with the reference technique (RThe performance of the IDS kit met the current recommendations and correlated strongly with the Cisbio method. The calculation of new sex-based reference values was needed to correctly classify patients according to androgen status, underlining the importance of systematically checking the reference values provided by suppliers.

International audience; Purpose: Measurement of prolactin in clinical laboratories is an important component in the management of patients with pituitary adenoma. Prolactin measurement is known to be sensitive to the high-dose hook effect, in the presence of extremely high prolactin concentrations. This interference is referred to in most recent articles discussing prolactin assays and the management of prolactin-secreting pituitary adenomas. The objective of our study was to evaluate if the high-dose hook effect remains relevant in current practice, when using currently available assays.Methods: Serum from a patient with a giant macroprolactinoma was assayed using all of the available prolactin assays in France in 2020, using native serum and after dilution. Technical inserts from assays were reviewed to assess the information on analytical principles, numbers of steps, and any reference to high dose hook effect.Results: Fourteen assay kits were studied by 16 laboratories; all were two-site immunometric assays, mostly using one step (11/14). Results obtained after dilution varied from 17,900 µg/L to 86,900 µg/L depending on the assay used. One tested assay was sensitive to the high-dose hook effect leading to a falsely lower prolactin concentration when measuring native serum (150 µg/L compared to 17,900 µg/L after dilution).Conclusion: The high-dose hook effect still exists in a very small minority of prolactin assays. The evolution of assay methods may lead to new assays that remain sensitive to this effect in the future. We therefore advise that the hook effect should still be mentioned in prolactin assay recommendations.

Multiple myeloma (MM) is a plasma cell malignancy characterized by clonal accumulation of malignant plasma cells in the bone marrow. CD38 is highly expressed on MM cells, and antibodies targeting CD38 (such as Isatuximab and Daratumumab) induce MM cell killing though several mechanisms, particularly by NK cell-mediated antibody dependent cellular cytotoxicity (ADCC). However, NK cells also express CD38 and treatment with anti-CD38 antibodies results in a rapid decrease of NK cells presumably due to fratricide, which may potentially limit NK cell mediated ADCC and reduce the efficacy of anti-CD38 antibody treatment. NK cells lacking CD38 in combination with Daratumumab have been shown to be resistant to NK cell fratricide and have improved ADCC. Here, we investigated the effect of knocking out CD38 in K-NK cells (CD38KO K-NK) in combination with Isatuximab. Peripheral blood NK cells were isolated from healthy donors and expanded using Kiadis PM21 particle technology (Oyer et al, Cytotherapy 2016) to produce highly activated K-NK cells. To produce CD38KO K-NK cells, CRISPR gene editing was applied during NK cell expansion by electroporating with Cas9/RNP complexes targeting CD38, and successful deletion of CD38 was confirmed by flow cytometry analysis. Analysis of key NK cell receptors by flow cytometry evidenced very similar receptor profiles between WT and CD38KO K-NK cells, suggesting that CD38 deletion does not affect the potent activation state of the K-NK cells. Importantly, CD38KO K-NK cells were found to be resistant to Isatuximab-induced fratricide. The cytotoxic activity of CD38KO K-NK cells in combination with Isatuximab against LP-1 and H929 MM cell lines was also measured. Calcein release assay and Incucyte based analysis revealed that cytotoxicity of CD38KO K-NK cells is enhanced in presence of Isatuximab, and that CD38KO K-NK cells are more cytotoxic than WT when combined with Isatuximab. Furthermore, the effect of Isatuximab/CD38KO K-NK cells combination also in association with SAR444245 (also termed THOR-707; Ptacin et al, Nat Commun 2021), an engineered non-α binding IL-2 that promotes NK cell activation and proliferation, was tested. Cytotoxicity of WT or CD38KO NK cells is enhanced in the presence of SAR444245. Indeed, addition of SAR444245 was found to further enhance the cytotoxic activity of CD38KO K-NK cells against LP-1 MM cells when combined with Isatuximab, resulting in an overall superior and sustained cytotoxicity. These data suggest that deletion of CD38 mitigates NK cell fratricide and improves Isatuximab-mediated ADCC against MM cells, and provide evidence for the therapeutic potential of the triple combination CD38KO NK cells, Isatuximab and SAR444245 in the setting of MM. Citation Format: Marco Meloni, Pauline Perrin, Erik Slinger, Chrissta Maracle, Alain Fournier, Nicole Acuff, Jill Mooney, Robert Y. Igarashi, Angela Virone-Oddos, Marielle Chiron. CD38KO K-NK cells prevent NK cell fratricide effect and improve isatuximab-mediated cytotoxicity against multiple myeloma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4209.

Introduction: Maternal TSH receptor antibodies (TRAbs) can cross the placenta and affect fetal and neonatal thyroid function. Maternal TSH receptor-blocking antibodies (TBAbs) are a rare cause of congenital hypothyroidism. Case Report: Following the discovery of a highly elevated TSH on her neonatal screening test, a 10-day-old girl with no familial history of thyroid disorder was referred to the pediatric endocrinology unit. Hypothyroidism was confirmed with a highly elevated TSH (817 mIU/L, reference range 0.4–3.1) and very low levels of FT4 (1.8 pmol/L, reference range 12–22). Anti-TPO antibodies were at 81 IU/mL (reference range Conclusion: We report herein a case of transient congenital hypothyroidism with a normal neonatal TRAbs level. In case of maternal TBAbs, similar activity of maternal TBAbs must be expected in the neonate, independently of the neonatal level of TRAbs.

Objectif Evaluer le reactif de dosage de testosterone libre (FT) du fournisseur IDS. Materiel et methodes La FT a ete mesuree sur une serie d’echantillons par immunodosage direct par chimiluminescence (iSYS, reactif IDS) et calculee via la formule de Vermeulen a partir des valeurs de testosterone totale (TT), de SHBG et d’albumine. La TT a ete mesuree par dosage RIA maison apres extraction et chromatographie et par technique directe (IDS), la SHBG par dosage IRMA (CisBio) ou CLIA (IDS) et l’albumine sur analyseur ABBOTT Alinity. Resultats Les echantillons de 45 hommes, d’âge median 31 ans (etendue : 15-61) ont ete analyses. Les medianes de TT etaient 13nmol/L (etendue : 2,8-41) en technique RIA et 16,25nmol/L (0,88-42,95) en immunodosage automatise. Les medianes de FT calculee a partir des valeurs de TT et de SHBG obtenues par RIA etaient 283 pmol/L (40,2-797) et par immunodosage automatise etaient 391 pmol/L (16,4-1020). La mediane de FT mesuree (IDS) etait 28 pmol/L (8-80 ; normes 10-720 pmol/L entre 10 et 20 ans, 4,86-74,54 pmol/L apres 20 ans). Discussion Les valeurs de FT mesurees sont 10 fois inferieures a celles calculees, representant environ 0,2 % de la TT au lieu des 1 a 2 % attendus. Certains recommandent de s’appuyer sur la FT, calculee ou mesuree par dialyse a l’equilibre, en cas de TT moderement abaissee [1] . Un regard critique doit etre porte sur les resultats de FT mesuree par immunodosage direct, cette technique n’etant pas recommandee.

Introduction Une femme de 64 ans a consulte en endocrinologie pour un bilan thyroidien perturbe (TSH : 5,25 mUI/L VR Observation Deux fournisseurs differents ont ete utilises : les analyses ont ete effectuees sur Cobas de ROCHE pour la FT4 et sur Architecte d’ABBOTT pour la TSH et la FT3. Les concentrations plasmatiques de la TSH, de la FT3 et de la FT4 etaient respectivement de 3,9 mUI/L (VR Discussion Les interferences analytiques liees a la presence d’anticorps heterophiles sont theoriquement prevenues par les fournisseurs par l’ajout d’agents bloquants dans les reactifs. Cette protection est parfois insuffisante et ce cas nous rappelle l’importance de la communication entre medecins cliniciens et biologistes dans l’interpretation des bilans et la recherche d’eventuelles interferences pour eviter toutes explorations supplementaires inutiles.

Le dosage du cortisol libre urinaire (CLU) est un des examens recommandes dans le diagnostic et le suivi du syndrome de Cushing. Objectif Evaluer un dosage d’immunoanalyse (IA) sans extraction par rapport a la technique de reference (chromatographie liquide couplee a la spectrometrie de masse LC-MSMS) dans le diagnostic mais aussi dans le suivi des traitements anticortisoliques. Materiels et methodes Les CLU ont ete doses en parallele par les deux techniques. L’IA est un dosage immunologique microparticulaire par chimiluminescence en une etape sans extraction (Architect-i2000 Abbott®). La LC-MSMS est effectuee sur un Agilent® Technologies 6460 Triple Quad LC/MS apres une extraction liquide-liquide sur support solide. L’etude a inclus 30 sujets controles, 62 patients hospitalises sans preselection et 9 patients diagnostiques, traites (par ketoconazole ou metyrapone) et suivis pour un syndrome de Cushing. Resultats Les valeurs de reference ont ete etablies avec les sujets controles : Conclusion Le dosage Cortisol-Abbott® est une technique d’immunoanalyse directe fiable pour le suivi des patients traites. La possibilite du rendu quotidien des CLU permet d’adapter le traitement au jour le jour.