The relationship between antinuclear antibody data and antibodies against extractable nuclear antigens in a large laboratory cohort.

Background: Anti-extractable nuclear antigen antibodies (anti-ENA) have diagnostic significance in systemic rheumatic disease (SRD).

Methods: Anti-ENA were tested in 1685/30,196 sera that were submitted sequentially for antinuclear antibody (ANA) testing. Frequency was stratified by ANA titer and pattern, by referral source, by submitted diagnosis and by patient age and sex.

The antinuclear antibody assay: developing criteria for reflexive anti-dsDNA antibody testing in a laboratory setting.

Background: We examined the relationship between antinuclear antibody (ANA) data and the presence of anti-double stranded DNA antibodies (anti-dsDNA).

Methods: De-identified demographic, ANA and anti-dsDNA data were available for 30,196 individuals aged ≥ 20 years, whose sera were submitted sequentially to our laboratory. When multiple sera were received for the same subject, data from the earliest sample were used.

Development and validation of 14 human serum protein assays on the Roche cobas® c 501.

Many laboratories rely on dedicated nephelometers and turbidimeters for the measurement of serum proteins. There are, however, a number of chemistry analyzers that offer open channel configurations for end-user applications. We developed and validated 14 human serum protein assays (α(1)-antitrypsin, α(2)-macroglobulin, albumin, apolipoproteins AI and B, complement components 3 and 4, haptoglobin, immunoglobulins A, G, and M, orosomucoid, transferrin, and transthyretin) on the Roche cobas(®) c 501.

Evaluation of the recombinant VlsE-based liaison chemiluminescence immunoassay for detection of Borrelia burgdorferi and diagnosis of Lyme disease.

Recent efforts to improve the serologic diagnosis of Lyme disease have included the use of a synthetic peptide (C6) that reproduces the sequence of invariable region 6 of VlsE, the variable surface antigen of Borrelia burgdorferi. In the present study, the diagnostic performance of DiaSorin's recombinant VlsE-based chemiluminescence immunoassay in 1,947 human serum samples was evaluated. Sensitivity was determined using two serum panels from the CDC.

Patient hydration: a major source of laboratory uncertainty.

Movement of body water from compartment to compartment during any time period is attributable to forces active within and upon each space. The result of these forces leads to transfer of water between intravascular and extravascular compartments, as well as shifts between extracellular and intracellular spaces. The importance of these shifts and of the associated mechanism was described by Ernest Starling in 1896 in very much the same manner as it is viewed today.

Serologic associations of anti-cytoplasmic antibodies identified during anti-nuclear antibody testing.

Background: There are currently no guidelines concerning additional laboratory testing for specific autoantibodies among anti-nuclear antibody-negative sera with an anti-cytoplasmic staining pattern identified by indirect immunofluorescence assay. Moreover, few data are available that address this laboratory situation.

Methods: We performed specific autoantibody assays in 200 sera with an anti-nuclear antibody titer < or =1:32 and a cytoplasmic titer (undefined staining pattern) of > or =1:64, identified sequentially in the course of routine anti-nuclear antibody testing.

Reference distributions for apolipoproteins AI and B and B/AI ratios: comparison of a large cohort to the world's literature.

Limiting the clinical utility of apolipoproteins AI (apo AI) and B (apo B) and the apo B/AI ratios until the last decade has been the lack of satisfactory methods for quantifying serum levels and credible reference materials. Great technological strides have been made in the last few years. The remaining barrier to more relevant and cost-effective use of serum protein data for diagnosis and prognosis has been the availability of widely recognized reliable reference intervals from birth to old age for both males and females.

Reference distributions for apolipoproteins AI and B and the apolipoprotein B/AI ratios: a practical and clinically relevant approach in a large cohort.

The two serum apolipoproteins in the highest concentrations, apolipoprotein (apo) AI and apolipoprotein B, and the apolipoprotein B/AI ratio are measured to assess clinical risk for atherosclerotic heart and peripheral vascular diseases. The study is based on a cohort of over 37,000 Caucasian individuals from northern New England measured in one laboratory by immunonephelometry using standardized reference materials. All samples received for protein analyses were accepted provided adequate identifying information was available.

Reference distributions for alpha2-macroglobulin: a practical, simple and clinically relevant approach in a large cohort.

In this 11th article in a series, reference values of serum levels alpha(2)-macroglobulin alpha(2)M) are examined. The study is based on a cohort of 40,420 Caucasian individuals from northern New England that were tested in our laboratory between 1994 and 2000. Measurements were standardized against Certified Reference Material (CRM 470)/Reference Preparation for Proteins in Human Serum (RPPHS) and the results analyzed using a previously described statistical approach.

Reference distributions for complement proteins C3 and C4: a practical, simple and clinically relevant approach in a large cohort.

The two serum proteins of the complement cascade in the highest concentrations, C3 and C4, respond to various conditions in much the same manner as do other positive acute-phase proteins. A major difference is that they are relatively sluggish in response to cytokine drive, requiring several days rather than hours to be detectably elevated by serial measurements. As with other acute-phase proteins, there are many processes that up- or down-regulate synthesis, including infection or inflammation, hepatic failure, and immune-complex formation.

Preanalytic and analytic sources of variations in C-reactive protein measurement: implications for cardiovascular disease risk assessment.

Background: C-reactive protein (CRP) is a widely recognized indicator of inflammation and is known to play an important role in atherogenesis. Recent prospective studies have demonstrated that increased CRP concentrations within the reference interval are a strong predictor of myocardial infarction, stroke, sudden cardiac death, and peripheral vascular disease in apparently healthy adults. On the basis of available evidence, the American Heart Association and the CDC have issued guidelines for the utility of CRP in the primary prevention of coronary heart disease and in patients with stable coronary disease or acute coronary syndromes.

Commutability of the CRM 470 C-reactive protein value in the Dade Behring N High Sensitivity CRP assay.

Certified Reference Material 470 (CRM 470) demonstrates commutability with both the manufacturer's calibrator and with dilutions of serum pools in the Dade Behring N High Sensitivity assay for C-reactive protein (CRP). Both regression and back calibration show similar nonlinearity for all materials, largely due to the method of calibration curve fitting used in this assay. Significant differences in values among the currently available commercial assays can be largely overcome by using appropriate calibration curve fitting and the recommended value transfer protocol, which includes a minimum of two assay runs on each of at least 3 separate days, with weight correction of all reconstitutions and dilutions.

Reference distributions for serum iron and transferrin saturation: a comparison of a large cohort to the world's literature.

The appropriate clinical use of serum iron and transferrin saturation (TSAT) requires satisfactory reference intervals from birth to old age, and for males and females. This study identified 54 publications from 1974 to 2001 that met the criteria used in three prior meta-analyses, and these were analyzed statistically. A summary of our review is presented along with our reference population data on these measurements.

Reference distributions for serum iron and transferrin saturation: a practical, simple, and clinically relevant approach in a large cohort.

The principal considerations driving iron status evaluation are clinical concern for anemia and the possibility of iron-storage disease. Most often, the circulating levels of transferrin (or total iron binding capacity) and serum iron are measured and the percentage of transferrin saturation (TSAT) is then computed. Optimally, reference ranges for these analytes should exclude the effects of the acute phase response, nutritional status, estrogen effect, specific genetic disorders, liver disease, and blood transfusion.

Development of immunoturbidimetric assays for fourteen human serum proteins on the Hitachi 912.

Many laboratories rely on dedicated nephelometers or turbidimeters and commercial reagent kits for the evaluation of serum proteins. However, with growing emphasis on cost containment, laboratories are forced to seek additional operational efficiencies by capitalizing on the use of existing analyzers whenever possible. In the present paper we describe the development of immunoturbidimetric assays for routine analysis of 14 human serum proteins (alpha1-antitrypsin, alpha2-macroglobulin, albumin, apolipoproteins Al and B, complement components 3 and 4, haptoglobin, immunoglobulins A, G, and M, orosomucoid, prealbumin, and transferrin) on the Hitachi 912, a general chemistry analyzer.