Establishment of detailed reference values for luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone during different phases of the menstrual cycle on the Abbott ARCHITECT® analyzer

During a normal menstrual cycle, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone can vary widely between cycles for the same woman, as well as between different woman. Reliable reference values based on the local population are important for correct interpretation of laboratory results. The purpose of our study was to determine detailed reference values for these hormones throughout the menstrual cycle using the Abbott ARCHITECT system. From 20 volunteers (age 20-36years) with normal cycles and no use of oral contraceptives, samples were taken every day during their cycle. Volunteers received three vaginal ultrasound examinations (days 10 and 13, and 1 or 2days after ovulation) to measure follicular and corpus luteum development. Hormone levels were measured using the corresponding ARCHITECT assay and were synchronized to the LH peak. Median, and 5th and 95th percentile values were determined for each day of the cycle, as well as for early follicular (days −15 to −6), late follicular (days −5 to −1), LH peak (day 0), early luteal (+1 to +4), mid-luteal (days +5 to +9), and late luteal (days +10 to +14) phases of the cycle. Based on our data, we were able to establish detailed reference values for LH, FSH, estradiol, and progesterone, which should aid in the interpretation of results for these reproductive hormones in a variety of circumstances. Clin Chem Lab Med 2006;44:883-

Clinico-pathological considerations in a 48-years-old female with acute kidney injury: is it lupus nephritis, ANCA-associated vasculitis or something else?

BACKGROUND: The value of ANCA positivity in the setting of systemic lupus erythematous and their pathogenicity remains uncertain. CASE PRESENTATION: We report the case of a 48-year-old female with rapidly progressive kidney failure, arthro-myalgia and weight loss. Auto-immune screening showed anti-dsDNA antibodies, complement consumption and triple ANCA positivity. A first kidney biopsy done at presentation highlighted class IV-G glomerulonephritis with elective extra-capillary involvement and mainly C1q glomerular deposition at immunofluorescence study. After three months of a regimen combining steroids and cyclophosphamide, a second biopsy was performed and showed class IV-G glomerulonephritis with mainly endocapillary proliferation. CONCLUSION: This case is atypical in view of immunological profile and kidney histopathological presentation and evolution and gives rise to discussion in view of recent data on ANCA value in lupus nephritis, and suggests that different auto-immune pathways may be involved in lupus nephritis

Apport des tests de quantification de la libération d’interféron gamma par les lymphocytes T sensibilisés pour le diagnostic des infections tuberculeuses

RésuméL’intradermoréaction cutanée à la tuberculine, couramment utilisée depuis un siècle pour le diagnostic d’infection tuberculeuse, présente de nombreux inconvénients. De nouveaux tests diagnostiques ont été récemment introduits. Ils mesurent soit la production d’interféron-γ dans le sang total, soit le nombre de lymphocytes T producteurs d’interféron-γ après stimulation in vitro par des protéines spécifiques de M. tuberculosis, absentes du BCG et de la plupart des mycobactéries atypiques. Le gain en spécificité permet de réduire les résultats faux positifs chez les sujets vaccinés, évitant ainsi le coût de chimioprophylaxies inutiles et potentiellement toxiques. Le gain en sensibilité, identifiant les infections tuberculeuses latentes parmi les sujets ayant une IDR faussement négative, permet d’accroître les performances diagnostiques dans les populations les plus à risques de progresser vers la tuberculose maladie, à savoir les patients immunodéprimés. L’évaluation de ces tests doit désormais se focaliser sur certains points qui restent à préciser : leur sensibilité chez l’enfant et le sujet immunodéprimé, leurs valeurs prédictives positive et négative et l’interprétation de leur variation éventuelle au cours du temps, que les patients soient traités ou non

Apport diagnostique du dosage des chaînes légères libres sériques d'immunoglobulines pour l'exploration des gammapathies monoconales

RésuméLes gammapathies monoclonales sont d\u27occurrence non négligeable (3,2 %) chez les sujets de plus de 50 ans. Pour environ la moitié d\u27entre elles, elles correspondent, lors de leur découverte, à une gammapathie monoclonale de signification indéterminée (ou MGUS en anglais pour monoclonal gammopathy of undetermined significance). Un peu plus du tiers sont des hémopathies lymphoïdes B avérées (myélome multiple, maladie de Waldenström, amylose) qui représentent le stade ultime de progression des MGUS avec une incidence annuelle de 1 %. L\u27exploration biologique immunologique validée à ce jour repose sur une analyse conjointe du sérum et des urines par immunoélectrophorèse/immunofixation qui vise à typer l\u27immunoglobuline monoclonale. Depuis 2001, un nouveau dosage est proposé pour la prise en charge diagnostique de ces patients : la détermination néphélémétrique ou turbidimétrique des chaînes légères libres (CLL) d\u27immunoglobulines kappa et lambda à l\u27aide d\u27anti-sérums spécifiques avec détermination du rapport κ/λ dont le déséquilibre peut être indicateur d\u27un excès de production monoclonale. Cela reste cependant un dosage quantitatif qui ne peut faire la preuve d\u27une anomalie qualitative (monoclonalité). L\u27apport pour le diagnostic et pour le suivi de ce dosage doit tenir compte des propriétés de la réaction antigène/anticorps en milieu liquide (phénomène de zone), du métabolisme rénal des chaînes légères avec ses conséquences en cas d\u27insuffisance rénale et des interférences possibles avec les chaînes légères liées des immunoglobulines intactes. L\u27apport diagnostique du dosage des CLL est patent dans les situations cliniques où l\u27absence de marqueur monoclonal peut être un handicap : myélome à chaîne légère, myélome apparemment non sécrétant, amylose et maladie de dépôt des chaînes d\u27immunoglobulines. Dans les autres situations (myélome à immunoglobuline intacte, MGUS), l\u27apport du dosage des CLL comme marqueur diagnostique ou comme indicateur de pronostic ou de suivi thérapeutique n\u27est pas encore prouvé. Son évaluation nécessitera des études prospectives particulièrement rigoureuses

Comparaison et intérêt des dosages des facteurs rhumatoïdes, des anticorps anti-filaggrine (anti-kératine) et des anticorps anti-peptides cycliques citrullinés dans la polyarthrite rhumatoïde

Objectifs : étudier la sensibilité et la spécificité du dosage sérique des facteurs rhumatoïdes (FR), des anticorps anti-peptides cycliques citrullinés (PCC) et des anticorps antikératine (AKA) vis-à-vis de la polyarthrite rhumatoïde (PR) ; les pathologies autres que la PR où au moins un de ces marqueurs est positif ; la signification de la fluorescence floconneuse des anticorps AKA en immunofluorescence indirecte (IFI). Méthode : deux cent quarante-huit patients ont été recrutés de manière rétrospective : 121 PR, 89 rhumatismes inflammatoires, 23 rhumatismes non inflammatoires et 15 affections non rhumatismales. Les FR ont été recherchés par néphélémétrie, les anti-PCC par immunofluorométrie et les AKA par IFI sur œsophage de rat. Résultats : les spécificités et sensibilités étaient respectivement : 68 % et 83 % pour le FR, 95 % et 76 % pour les anti-PCC, 83 % et 40 % pour les AKA dans les PR d’évolution de moins d’un an. Les taux de concordances suivants ont été observés : FR versus PCC : 81 %, FR versus AKA : 57 %, PCC versus AKA : 73 %. Douze patients ayant une pathologie différente de la PR ont des anti-PCC ou des AKA positifs. Trente-trois pour cent des patients avec des anti-PCC supérieurs à 130 U/mL avaient des AKA floconneux contre seulement 5 % quand les anti-PCC sont inférieurs à 130 U/mL. Conclusion : les recherches des FR et des anti-PCC sont complémentaires dans la PR. D’autres pathologies auto-immunes et néoplasiques peuvent parfois être responsables de la positivité des anti-PCC et des AKA. L’aspect floconneux des AKA en IFI peut être associé à des concentrations élevées en anti-PCC

Increased cerebral blood flow velocities assessed by transcranial Doppler examination is associated with complement activation after cardiopulmonary bypass

The role of complement activation on the cerebral vasculature after cardiopulmonary bypass (CPB) is unclear. The goal of the study was to assess whether heparin-coated CPB reduces complement activation, and influences cerebral blood flow velocities (CBFV). Twenty-four patients undergoing coronary surgery were randomly allocated to non-coated (NC-group) or heparin-coated (HC-group) CPB. Complement activation was assessed by measuring sC5b-9. Transcranial Doppler (TCD) was performed on middle cerebral arteries before and after CPB. Systolic (SV), diastolic (DV) and mean (MV) CBFV were measured. Significant increase of sC5b-9 (p=0.003) was observed in the NC-group and CBFV increased after CPB (SV by 27%, p=0.05; DV by 40%, p=0.06; MV by 33%, p=0.04) whereas no changes were detected in the HC-group. TCD values were higher in the NC-group than in the HC-group (SV, p=0.04; DV, p=0.03; MV, p=0.03) although cardiac index, systemic vascular resistance, haematocrit and pCO2 were similar. Postoperative SV, DV and MV were significantly correlated with sC5b-9 (r=0.583, p=0.009; r=0.581, p=0.009; r=0.598, p=0.007, respectively). Increased CBFV after CPB are correlated to the level of complement activation and may be controlled by heparin-coated circuits

CCR7 is involved in the migration of neutrophils to lymph nodes

Increasing evidence suggests that neutrophils may participate in the regulation of adaptive immune responses, and can reach draining lymph nodes and cross-prime naive T cells. The aim of this study was to identify the mechanism(s) involved in the migration of neutrophils to the draining lymph nodes. We demonstrate that a subpopulation of human and mouse neutrophils express CCR7. CCR7 is rapidly expressed at the membrane upon stimulation. In vitro, stimulated human neutrophils migrate in response to the CCR7 ligands CCL19 and CCL21. In vivo, injection of complete Freund adjuvant induces a rapid recruitment of neutrophils to the lymph nodes in wild-type mice but not in Ccr7−/− mice. Moreover, intradermally injected interleukin-17–and granulocyte-macrophage colony-stimulating factor–stimulated neutrophils from wild-type mice, but not from Ccr7−/− mice, migrate to the draining lymph nodes. These results identify CCR7 as a chemokine receptor involved in the migration of neutrophils to the lymph nodes

FibroMeters: a family of blood tests for liver fibrosis with high diagnostic performance and applicability in clinical practice

International audienc

Hypogammaglobulinemia and risk of severe infection in kidney transplant recipients

Background Recent data have outlined a link between hypogammaglobulinemia (HGG) and infection risk and suggested that HGG correction may decrease post‐transplant infections. Methods We analyzed the risk factors of HGG and the relationship between HGG and the risk of severe infection in a cohort of 318 kidney transplant recipients (KTR) who were transplanted between 2003 and 2013. Immunoglobulin (Ig) concentration was measured prospectively at day 15 (D15), month 6 (M6), month 12 (M12), and month 24 (M24) post transplant. Results The prevalence of IgG HGG was 56% and 36.8% at D15 and M6, respectively. Age was the sole identified risk factors for D15 IgG HGG (odds ratio [OR] 1.02, P = 0.019). Risk factors for M6 IgG HGG were the presence of D15 IgG HGG (OR 6.41, P < 0.001) and treatment of acute rejection (OR 2.63, P = 0.014). Most infections occurred between D15 and M6 post transplant. Only age (hazard ratio 1.03, P < 0.001) was identified as a risk factor of infection between D15 and M6 post transplant. Survival free of infection (overall infections and bacterial or viral infections) did not differ significantly between patients with or without D15 IgG HGG. Only septicemia occurring between M6 and M12 post transplant was more frequently observed in patients with HGG. The low prevalence of severe HGG (<400 mg/dL) did not allow conclusions on the infectious risk associated with this patient subgroup. Conclusions This study does not support the existence of a strong link between post‐transplant HGG and the risk of severe infections in KTR. Correction of HGG to minimize the risk of severe infections in KTR is thus questionable and needs to be reevaluated in prospective studies

Reproducibility of blood tests of liver fibrosis in clinical practice

Objectives:To evaluate the inter-laboratory reproducibility of blood test for liver fibrosis: FibroMeter, Fibrotest, APRI and their composites variables. Design and methods: Four studies, including 147 patients, were performed: study #1 included 2 metachronous blood samples and 2 laboratories; studies #2, #3 and #4 included synchronous samples with assays delayed at day 1 in 12 laboratories, at day 0 in 10 laboratories and at day 0 or 1 in 2 laboratories, respectively. Agreement was evaluated by the intraclass correlation coefficient (ric). Results: In studies #1, #2 and #4, ric for FibroMeter was 0.893, 0.942 and 0.991, respectively. In study #3, the ric were: FibroMeter: 0.963, Fibrotest: 0.984, APRI: 0.949. Large simulated variations in composite variables had a weak impact on FibroMeter. Conclusions: When blood marker limits are controlled, inter-laboratory agreement of blood tests is excellent in clinical practice conditions. Blood tests are robust against the variability of composite blood variables