[Introducing the new international vocabulary of metrology]. / Présentation du nouveau Vocabulaire international de métrologie.

The 3rd edition of the "International vocabulary of metrology - Basic and general concepts and associated terms (VIM)" is a fundamental document for the people who are concerned by metrology. This international standard is bilingual (french/english). The VIM contains definitions of metrological concepts, their hierarchy, numerous explicative notes and examples. This approach confirms that the concepts of the VIM are applicable to various disciplines including clinical laboratory sciences.

[Glossary of the acronyms for the institutions concerned by metrology]. / Glossaire des acronymes d'institutions relevant de la métrologie.

Metrology and one of its contributions, metrological traceability represent two fundamental developments for the clinical laboratories. Several international and national institutions take part in these developments. They elaborate recommendations going from concepts to implementation in the clinical laboratories. These activities are helpful for accrediting clinical laboratories.

Qualitative immunoglobulin abnormalities in HIV-positive patients: long-term follow-up.

We studied the immunoglobulins of a cohort of 212 HIV-positive patients followed-up for 13 years. The qualitative study of immunoglobulins by immunoelectrophoresis and immunofixation distinguished three groups of patients: those with monoclonal immunoglobulins, those with minor abnormalities of immunoglobulins and those with polyclonal immunoglobulins. We characterized these groups according to age, sex, immunoglobulin isotypes, and survival curves. The results show that this population of immunoglobulinopathies has distinctive characteristics. In particular, the presence of immunoglobulin abnormalities has no significant prognostic value.

Implication of the first and third extracellular loops of the mu-opioid receptor in the formation of the ligand binding site: a study using chimeric mu-opioid/angiotensin receptors.

Recent studies on chimeric mu/delta-, mu/kappa- and delta/kappa-opioid receptors have suggested that extracellular loops of the receptors were involved in the discriminatory binding of selective ligands by controlling their entry into the transmembrane binding site. Since homochimeric opioid receptors are mostly informative in terms of selectivity, the role of extracellular loops was examined here by studying heterochimeric mu receptors where the totality or parts of extracellular loops were replaced by the corresponding regions of the receptor for angiotensin II. Chimeric mu receptors with extracellular loop EL1 or EL3 originating from the angiotensin receptor had 100-fold decreased affinities for opioids; the length of the first extracellular loop, which is one residue longer in angiotensin than mu receptors, was shown to be responsible for this situation. Substitution of the mu receptor second extracellular loop by that of the angiotensin receptor diminished by approximately 10-fold the affinities for opioids. Since all chimeras had altered affinities for selective and nonselective ligands, we propose that extracellular domains of the mu receptor, particularly the first and third loops, constrain the relative positioning of the connected transmembrane domains where selective as well as nonselective contact points form the opioid binding site.

Biclonal immunoglobulin M dysglobulinaemia: evolving aspects in a case of primary Sjögren's syndrome.

The observation of suggestive clinical symptoms in a patient suffering from a Gougerot-Sjögren syndrome led to a search for a cryoglobulin. Unusual physico-chemical features of this cryoglobulin were discovered, using standard electrophoresis, immunoelectrophoresis, immunofixation and electroimmunotransfer. The main unusual finding was that the cryoprecipitate was made up of a biclonal IgM kappa associated to polyclonal IgG. Therefore, we suggest that this new form of cryoglobulin be classified as a subtype IIb, thus distinguishing two subtypes in the usual classification.

[Improvements from the reference material CRM 470 in the standardization of the determination of serum proteins]. / Améliorations apportées par le matériau de référence CRM 470 dans la standardisation du dosage des protéines sériques.

The introduction of the CRM 470 in 1993 (certified reference material for 14 serum proteins) and its utilization by industrial companies for cross-calibrating their commercial standards has been an important break-through in protein standardization. This improvement has been clearly illustrated by the last national quality control survey performed in France in may 1995. At this time, about 60% of the 1,870 participants have already adopted the new standardization. The between-run precision (interlaboratory and intertechnique) has been considerably improved by the use of the new international standard (5.8 to 12.2% versus 10 to 24.1% before standardization); the same is true for accuracy. These results should convince the last reluctant laboratories to adopt the new standardization. Thus, it seems now possible to define reference ranges for serum proteins: this is the new task assigned to the Committee for Plasma Protein Standardization of the IFCC.

[Serum determination of IgG, IgA, IgM, transferrin and haptoglobin. I. Attempt at normalization of results]. / Dosages sériques d'IgG, IgA, IgM, transferrine et haptoglobine. I. Essai d'harmonisation des résultats.

This study demonstrates the advantages and limitations of normalizing results for five serum proteins (IgG, IgA, IgM, transferrin and haptoglobin), analysed in liquid phase on ten different systems (open clinical chemistry and dedicated protein analysers). Seven sets of results from normal and pathological sera (without monoclonal proteins) were compared using: - calibrators supplied by each manufacturer; - - serial dilutions of a single stabilized pool of liquid serum. In addition to validating the quality of the stabilised serum, we have been able to identify: - significant variations in results using different analytical systems for the same sample; - a major reduction in these variations, often greater than 50%, through normalization using a common serum pool. In some two thirds of the cases, this reduction brought the degree of variation into an acceptable range.

[Serum levels of IgG, IgA, IgM, transferrin and haptoglobin. III. Results obtained with monoclonal immunoglobulins]. / Dosages sériques d'IgG, IgA, IgM, transferrine et haptoglobine. III. Résultats obtenus en présence d'immunoglobulines monoclonales.

This study is the third part of a multicenter evaluation carried out with ten analysers. Five proteins (IgG, IgA, IgM, transferrin, haptoglobin) were assayed in three sera, each containing one monoclonal Ig (IgG, IgA, or IgM). The expected agreement was not obtained with these particular sera, except in the case of haptoglobin. The marked imprecision of the monoclonal Ig quantification is highlighted, including the fact that many erroneous results are due to the antigen excess phenomenon. It is also shown that in the serum containing monoclonal IgM, quantification of the other proteins, remaining polyclonal Ig, as well as transferrin and haptoglobin, is difficult. The authors recall that electrophoresis and immunoelectrophoresis, which are indispensable for the characterization of the monoclonal components, are of great help in solving such difficulties.

[Reference material (CRM 470) for serum proteins: preparation, characteristics and conditions of use]. / Le matériau de référence (CRM 470) pour les protéines sériques: préparation, caractéristiques et conditions d'utilisation.

Several national and international quality assurance schemes clearly demonstrated the discrepancies between the results given by different analytical systems designed for the immunochemical measurement of proteins. Thus, the need for the preparation of a new international secondary reference material appeared urgent to the International Federation for Clinical Chemistry (IFCC). In this paper, the authors describe the different steps of the preparation of the new standard CRM 470. This work financed by the Bureau Communautaire de Référence (BCR) has been done in collaboration with the College of American Pathologists (CAP). The physicochemical properties of the proteins present in the CRM 470 and the various controls undertaken on the preparation are described. The CRM 470 material (40,000 lyophylised 1 ml vials) is now certified for the 14 plasma proteins of major interest in clinical chemistry. The worldwide introduction of this material will considerably improve the accuracy of immunochemical proteins' determination and will allow the determination of the reference values as a function of age and sex.

[Multicenter study of commercial kits for the determination of human IgG subclasses, using the ELISA technique]. / Etude multicentrique des trousses commercialisées pour le dosage des sous-classes d'IgG humaines par technique ELISA.

We evaluated two commercially available sandwich type Elisa procedures for the measurement of IgG subclasses in human serum. Assay kits from The Binding Site and the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service were tested in six laboratories. The performance of spectrophotometers, pipettes and dilutors were assessed at each center. Within-run precision was estimated according to the Valtec method (Société Française de Biologie Clinique). The overall coefficient of variation ranged from 4 to 50% depending on subclass and kit. We also evaluated the IgG2 and IgG4 specificity using four sera containing a monoclonal IgG2 or IgG4 (kappa or lambda type). Using total IgG and immunoelectrophoresis as a comparative technique, IgG2 kappa and IgG4 kappa were both underestimated, IgG2 lambda was overestimated while IgG4 lambda compared favorably. Polyclonal IgG subclasses were frequently overestimated in these sera suggesting cross-reactions with either monoclonal IgG or other polyclonal IgG. Antigen excess was investigated and not encountered with either kit. Our results demonstrate that these procedures are insufficiently accurate or precise for routine clinical use.