Evaluation of cryoprotein investigation using a digital external quality assurance scheme.

Robust preanalytical and analytical processes are critical for the detection of cryoproteins. There is significant variation in practice in the detection, analysis and reporting. A survey in 2018 of 137 laboratories participating in the UK National External Quality Assessment Service (UK NEQAS) (6) quality control program showed significant variation in the laboratory processes which highlighted the need for standardisation of the detection, analysis and reporting of cryoglobulins.

Development of a certified reference material for anti-β2-glycoprotein I IgG - commutability studies.

Objectives: In this paper, we describe the steps followed for the development of a certified reference material for immunoglobulin G antibodies against β2-glycoprotein I (also known as apolipoprotein H). These steps include processing of the material, commutability, the impact of dilution, the appropriate reconstitution conditions, homogeneity and stability during transport and storage.

Methods: We analysed 69 clinical samples from patients suffering from antiphospholipid syndrome with several commercial enzyme-linked immunosorbent assays (ELISA) purchased from in vitro diagnostic manufacturers.

Certified reference material against PR3 ANCA IgG autoantibodies. From development to certification.

Background The importance of the standardisation of immunoassays for autoantibodies has been widely discussed. The appropriate use of certified reference materials (CRM) could contribute to a more accurate diagnosis and follow-up of a series of diseases such as small vessel-associated vasculitis. This is a systemic autoimmune disorder during which two autoantibodies can be present, MPO ANCA IgG and PR3 ANCA IgG.

Large abnormal peak on capillary zone electrophoresis due to contrast agent.

Background Some iodinated radio-contrast media absorb ultraviolet light and can therefore be detected by capillary zone electrophoresis. If seen, these peaks are typically small with 'quantifications' of below 5 g/L. Here, we describe the detection of a large peak on capillary zone electrophoresis that was due to the radio-contrast agent, Omnipaque™.

Electrophoretic patterns post daratumumab.

Background Daratumumab (Darzalex) is a human IgG1 kappa monoclonal antibody targeting CD38 that has been recently approved for the treatment of refractory multiple myeloma. As it is a monoclonal protein, it can be detected on routine serum protein electrophoresis and by immunofixation. Methods Serum samples from four patients were analysed by serum protein electrophoresis immediately pre- and post-treatment with daratumumab.

Development of a Certified Reference Material for myeloperoxidase-anti-neutrophil cytoplasmic autoantibodies (MPO-ANCA).

A serum Certified Reference Material (CRM) for supporting reliable autoimmune diagnostics was recently released by the Institute for Reference Materials and Measurements (IRMM) of the Joint Research Centre of the European Commission. It was produced in collaboration with a Working Group on the Harmonisation of Autoimmune Tests of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC WG-HAT). This material is aimed at facilitating the standardisation of measurements of anti-myeloperoxidase immunoglobulin G antibodies.

Strategies for building reference standards for autoantibodies.

Producing robust, certified, traceable reference material for autoantibody testing is a vital element in maintaining the validity of results that are generated in the daily clinical laboratory routine. This is a huge challenge because of the high number of variables involved in the detection and measurement of the autoantibodies. The production of such materials is time consuming and needs rigorous attention to detail; this is best achieved by an overarching independent body who will oversee the process in a "not for profit" manner.

Standardization of autoantibody testing: a paradigm for serology in rheumatic diseases.

Autoantibody measurement is an excellent tool to confirm the diagnosis of rheumatic autoimmune diseases. Hence, reliability and harmonization of autoantibody testing are essential, but these issues are still a matter of debate. Intrinsic variability in analytes and reagents as well as heterogeneity of the techniques are the main reasons for discrepancies in inter-laboratory variations and reporting of test results.

The importance of commutability of reference materials used as calibrators: the example of ceruloplasmin.

Background: Different methods for ceruloplasmin tend to give different results in external quality assessment schemes. During the production of the certified reference material ERM-DA470k/IFCC discrepant measurement results were also found for ceruloplasmin measured with different methods, and consequently the protein could not be certified in the material.

Methods: We performed a commutability study with 30 serum samples and the reference materials ERM-DA470, ERM-DA470k/IFCC, and ERM-DA472/IFCC, using 6 different methods.

Standardizing plasma protein measurements worldwide: a challenging enterprise.

The need for harmonizing laboratory results is particularly intense in the field of quantitative protein assays in consideration of the clinical impact of specific protein measurements and their relevance in monitoring disease. We report the efforts made by the Committee on Plasma Proteins of the IFCC Scientific Division to achieve worldwide comparability in plasma protein results. We focus on the production of reference materials and the methods applied throughout their production process.

Characterization of the new serum protein reference material ERM-DA470k/IFCC: value assignment by immunoassay.

Background: The availability of a suitable matrix reference material is essential for standardization of the immunoassays used to measure serum proteins. The earlier serum protein reference material ERM-DA470 (previously called CRM470), certified in 1993, has led to a high degree of harmonization of the measurement results. A new serum protein material has now been prepared and its suitability in term of homogeneity and stability has been verified; after characterization, the material has been certified as ERM-DA470k/IFCC.

Early-pregnancy multiple serum markers and second-trimester uterine artery Doppler in predicting preeclampsia.

Objective: To estimate the ability of maternal serum markers and uterine artery Doppler in predicting preeclampsia.

Methods: In this nested case-control study, maternal serum concentrations of cystatin C, beta2-microglobulin, serum amyloid A, C-reactive protein (CRP), and neopterin were measured, and resistance index of uterine artery blood flow was assessed in 45 women in whom preeclampsia subsequently developed and in 125 women with normal pregnancy outcome. Univariable regression analysis was performed to estimate correlations between serum markers and resistance index for the development of preeclampsia.

Development and preparation of a new serum protein reference material: feasibility studies and processing.

Background: The availability of matrix reference materials is essential for the standardisation of (immuno)assays used to measure proteins. The reference material ERM-DA470 (previously called CRM470) certified in 1993 has led to a large degree of harmonisation of these assays. A new serum protein reference material has now been produced (ERM-DA470k).

Raised maternal serum cystatin C: an early pregnancy marker for preeclampsia.

The balance between trophoblast cathepsin and decidual cystatin C expression is pivotal in physiological trophoblast development. Defective trophoblast invasion is characteristic of preeclampsia and may involve derangement of the cathepsin/cystatin C balance. We conducted a prospective nested case-control study of healthy women with singleton pregnancies in the first trimester of pregnancy.

Serum alpha 2-HS glycoprotein predicts survival in patients with glioblastoma.

Background: Glioblastoma, the most common primary brain tumor, has variable prognosis. We aimed to identify serum biomarkers that predict survival of patients with glioblastoma.

Methods: In phase 1 (biomarker discovery), SELDI-TOF mass spectra were studied in 200 serum samples from 58 control subjects and 36 patients with grade II astrocytoma, 15 with anaplastic astrocytoma, and 91 with glioblastoma.

Identification of a novel Haemophilus influenzae protein important for adhesion to epithelial cells.

Non-typable Haemophilus influenzae (NTHi) is an important human-specific respiratory pathogen colonizing the mucosa of the upper respiratory tract. The bacterium is a common cause of acute otitis media in children and exacerbations in patients with chronic obstructive pulmonary disease (COPD). An immunoglobulin (Ig) D-lambda myeloma protein was found to detect a 16 kDa surface protein that we designated protein E (PE).