[Validation of a method for measuring the antielastolytic activity of human circulating alpha1-antitrypsin].

The existence of alpha-1 antitrypsin variants with apparently unremarkable phenotypes and serum concentrations, contrasting with a clinical picture suggestive of a severe deficiency, led us to investigate whether in these cases there was a reduction or even suppression of the capacity of alpha-1 antitrypsin to inhibit elastase. To this end, in two different laboratories, we adapted and validated a method for measuring the functional activity of alpha-1 antitrypsin, based on spectrophotometric kinetic analysis of the inhibition by serum alpha-1 antitrypsin of the hydrolytic activity of porcine pancreatic elastase on a chromogenic substrate. This method has proved to be robust, reproducible and transferable and made possible to define, on the basis of an analysis of a hospital population, a functionality index with a confidence interval comprised between 0.

[Screening for alpha1-antitrypsin deficiency using dried blood spot: Assessment of the first 20 months].

Introduction: Alpha1-antitrypsin deficiency is a predisposing factor for pulmonary disease and under-diagnosis is a significant problem. The results of a targeted screening in patients with respiratory symptoms possibly indicative of severe deficiency are reported here.

Methods: Data were collected from March 2016 to October 2017 on patients who had a capillary blood sample collected during a consultation with a pulmonologist and sent to the laboratory for processing to determine alpha1-antitrypsin concentration, phenotype and possibly genotype.

Assessment of liver fibrosis by transient elastography (Fibroscan) in patients with A1AT deficiency.

Background: Alpha-1-antitrypsin deficiency (A1ATD) is a common genetic condition which predisposes to emphysema and liver disorders. It is estimated that 10-15% of homozygous individuals for the Z allele (PiZZ) may develop liver fibrosis. The optimal modalities to detect liver disease in PiZZ adult patients need to be defined.

Liver disease related to alpha1-antitrypsin deficiency in French children: The DEFI-ALPHA cohort.

Background & Aims: To identify prognostic factors for liver disease in children with alpha-1 antitrypsin deficiency, irrespective of phenotype, using the DEFI-ALPHA cohort.

Methods: Retrospective, then prospective from 2010, multicentre study including children known to have alpha-1 antitrypsin blood concentration below 0.8 g/L, born in France since 1989.

Description of 22 new alpha-1 antitrypsin genetic variants.

Alpha-1 antitrypsin deficiency is an autosomal co-dominant disorder caused by mutations of the highly polymorphic SERPINA1 gene. This genetic disorder still remains largely under-recognized and can be associated with lung and/or liver injury. The laboratory testing for this deficiency typically comprises serum alpha-1 antitrypsin quantification, phenotyping according to the isoelectric focusing pattern and genotyping if necessary.

Elevated IgG4 serum levels in patients with cystic fibrosis.

Objective: Serum immunoglobulin (Ig) G4 elevation has been associated with several pathological conditions other than IgG4-related disease (IgG4-RD). In cystic fibrosis (CF), an elevation of specific IgG4 has been associated with colonization and infection by Pseudomonas aeruginosa. IgG4 elevation may be a marker of chronic infection or inflammatory stimulation.

SERPINA1 and MAN1B1 polymorphisms are not linked to severe liver disease in a French cohort of alpha-1 antitrypsin deficiency children.

Background & Aims: Fifteen to twenty percent of alpha-1 antitrypsin deficiency patients (A1ATD) have a severe liver outcome (portal hypertension - PHT) during childhood. Since they all share the same ZZSERPINA1 genotype and that environmental factors such as alcohol cannot be advanced, the presence of modifier genes is now well recognized. SNPs located on the SERPINA1 and MAN1B1 genes have already been tested in very few studies with contradictory or not replicated results.

Heavy+light chain monitoring correlates with clinical outcome in multiple myeloma patients.

Novel anti-myeloma agents have improved patient response rates, which are historically based on reductions of the M-protein. These methods can be inaccurate for quantifying M-proteins at low concentrations. We compared the consistency and clinical impact of response assignment by electrophoretic and heavy+light chain (HLC) immunoassays post-consolidation in 463 newly diagnosed patients.

Clinical heterogeneity and potential high pathogenicity of the Mmalton Alpha 1 antitrypsin allele at the homozygous, compound heterozygous and heterozygous states.

Background: Alpha 1 antitrypsin (A1AT) deficiency (A1ATD) is potentially associated with a high degree of liver and/or lung disease. Apart from the most frequent deficiency alleles, Pi S and Pi Z, some A1AT alleles of clinical significance may be easily misdiagnosed. This is typically the case of the Pi Mmalton variant which shares the same 'gain-of-function' liver toxicity than Pi Z and the same 'loss of function' lung disease as well.

[DEFI-ALPHA cohort and POLYGEN DEFI-ALPHA clinical research hospital programme. A study about clinical, biological and genetics factors associated with the occurrence and the evolution of hepatic complications in children with alpha-1 antitrypsin deficiency].

Introduction: The alpha-1 antitrypsin (α1-AT) deficiency, most frequently caused by homozygosity for the Z variant (SERPINA1: c.1096 G>A; Glu342Lys), can give rise to two clinical patterns: (i) respiratory impairment with emphysema (mainly in adulthood) because of a pulmonary quantitative defect in anti-elastase activity; (ii) hepatic impairment (mainly in childhood) due to the misfolding of the PiZ protein which accumulates in hepatocytes thus providing cytotoxicity.

Current Knowledge: To date, the clinical and genetic factors responsible for the development of major hepatic injuries (fibrosis and portal hypertension) during childhood in PiZ patients are not known.

[Development of a laboratory test on dried blood spots for facilitating early diagnosis of alpha-1-antitrypsin deficiency].

Alpha- 1-antitrypsin (A1AT) deficiency is a hereditary autosomal codominant genetic disorder resulting in low circulating levels of A1AT and leading to lung and/or liver disease. It remains underdiagnosed and only 5 to 10% of PIZZ patients, the most common form of severe A1AT deficiency, would be actually identified in France. Facilitating early diagnosis of A1AT deficiency would allow a better management of this disease; therefore we have developed and standardized in three laboratories involved in this study, a diagnostic test on dried blood spots (DBS) including quantitative A1AT measurement, phenotyping by IEF electrophoresis and, if necessary, genotyping by SERPINA1 gene sequencing.

Creatinine- versus cystatine C-based equations in assessing the renal function of candidates for liver transplantation with cirrhosis.

Unlabelled: Renal dysfunction is frequent in liver cirrhosis and is a strong prognostic predictor of orthotopic liver transplantation (OLT) outcome. Therefore, an accurate evaluation of the glomerular filtration rate (GFR) is crucial in pre-OLT patients. However, in these patients plasma creatinine (Pcr) is inaccurate and the place of serum cystatine C (CystC) is still debated.

[Place of genotyping in addition to the phenotype and the assay of serum α-1 antitrypsin].

The diagnosis of deficiency of alpha-1 antitrypsin (A1AT) is based on isoelectric focusing of serum proteins and the extent of serum. However, the focusing is technically difficult and a greatly reduced concentration in abnormal A1AT tapeless does not differentiate an unstable variant of a variant called 'null' (that is to say without any phenotypic expression) to 'heterozygous' state. In this study, we compared the results of the assay, the phenotype and genotype of A1AT in 50 patients.

The best way to detect elevated albuminuria.

Background: It has been reported that first morning specimens are more reliable than random spot specimens to assess 24-hour urinary albumin excretion rate (UAER), especially if albuminuria is expressed as albuminuria to creatininuria ratio. We aimed to investigate the influence of (a) posture and activity and (b) the units to best estimate 24-hour albuminuria.

Methods: In this retrospective study, 24-hour UAER was compared to 60 min 'supine' and 90 min 'activity' albuminuria in 124 patients tested for resistant hypertension.

Prolonged hemodialysis for acute kidney injury in myeloma patients.

Objective: Cast nephropathy, due to free light chain (FLC) toxicity, is the main cause of acute kidney injury in multiple myeloma, with about 10% of patients requiring dialysis. In these patients, in addition to chemotherapy that prevents FLC production, daily hemodialysis using high cutoff or adsorptive membranes, showed promising results by decreasing quickly toxic serum FLC concentrations.

Case History: We report here the case of 2 patients presenting with acute kidney injury and high FLC serum concentration and M-components one with IgG Kappa and the other with IgD lambda.

Clinical manifestations of staphylococcal scalded-skin syndrome depend on serotypes of exfoliative toxins.

We sought a possible correlation between the clinical manifestations of staphylococcal scalded-skin syndrome (SSSS) and the serotype of exfoliative toxins (ET) by PCR screening of the eta and etb genes in Staphylococcus aureus strains isolated from 103 patients with generalized SSSS and 95 patients with bullous impetigo. The eta gene and the etb gene were detected in, respectively, 31 (30%) and 20 (19%) episodes of generalized SSSS and 57 (60%) and 5 (5%) episodes of bullous impetigo. Both genes were detected in 52 (50%) episodes of generalized SSS and 33 (35%) episodes of bullous impetigo.

Oligo-monoclonal immunoglobulins frequently develop during concurrent cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections in patients after renal transplantation.

In the present study we report that the appearance of oligo-monoclonal immunoglobulins (oligoM-Igs) in the sera of transplanted individuals is concurrent with the detection of coincident active CMV infection and EBV replication. Eighty-four renal allograft patients were monitored with respect to CMV isolation, to CMV conventional serology and humoral response against the EBV trans-activator ZEBRA (an immediate-early antigen also called BZLF1). Titration of anti-ZEBRA antibodies (IgG and IgM) and amount of EBV DNA in serum were evaluated.

[Immunonephelometric analysis of immunoglobulin light chains: agreement between the theoretical and experimental model. Assessment of the reference values of the kappa/lambda ratio and the heavy to light chain ratio].

Since the introduction of fully automated nephelometric systems simultaneous measurements of immunoglobulin light chains kappa (kappa) and lambda (lambda) and IgG, IgA and IgM have become increasingly used for the routine assessment of humoral immunity. From these data two ratios were calculated, the kappa/lambda ratio and the heavy chains to light chains ratio. As changes in these ratios might have some predictive clinical value besides reflecting a monoclonal component, it is necessary to know mean and reference limits of these ratios.

Plasma cell proliferation in monoclonal gammopathy: relations with other biologic variables--diagnostic and prognostic significance.

Purpose: We investigated the place of direct plasma cell proliferation analysis beside other biologic data in monoclonal gammopathy, particularly the serum level of C-reactive protein (C-RP) PATIENTS: Eighty patients were studied at the time of their diagnosis. Patients with a serum creatinine level greater than 200 mumol/L were excluded.

Methods: Plasma cell proliferation analysis was performed after bromodeoxyuridine incorporation and double immunoenzymatic labeling on cytological smears, making determination of the plasma cell labeling index (LI) possible.

Tobacco smoking and other factors in relation to serum alpha-1-antitrypsin.

Serum levels of alpha-1-antitrypsin were measured by radial immunodiffusion, and phenotypes were determined by electrofocusing in acrylamide gel in 160 subjects who were used as controls in a case-control study of hepatocellular carcinoma (HCC). The results were studied in relation to age, sex, diagnostic category, tobacco smoking, consumption of alcoholic beverages, presence of hepatitis B surface antigen (HBsAg), and serum levels of alphafetoprotein (AFP) by modeling the data through multiple regression. There was no relation of serum alpha-1-antitrypsin values with sex, HBsAg, AFP, consumption of alcoholic beverages, and diagnostic category (p > 0.