Immunodiagnostics and Patient Safety

✍ Scribed by Krystyna Sztefko

• Publisher: De Gruyter
• Year: 2011
• Tongue: English
• Leaves: 176
• Series: Patient Safety; 3
• Category: Library

✦ Synopsis

Today most of immunochemistry methods for the determination of proteins, peptides, drugs, and many small molecules are fully automated, with good precision, excellent sensitivity and short reaction time. However, inaccuracy due to poor standardization and the presence of interfering substances in biological samples is still a serious and life-threatening issue. Proper validation of methods and quality assurance have little effect on frequency of occurrence of false positive or false negative results, which, if unrecognized, may lead to patient's misdiagnosis, unnecessary treatment or even unnecessary surgery. Deep knowledge of basic principles of immunochemical methods (antigen-antibody reaction, standardization, matrix effect, limit of detection, cross-reactivity, etc.), sources of analyte-independent interferences (preanalitycal errors, the presence of binding proteins, the presence of autoantibodies) and analyte-dependent interferences (presence of heterophilic antibodies, high-dose effect) are very important to understand, detect, reduce and/or eliminate the interferences. This book helps to reduce false results and, at the same time, improve patient's care and patient's safety.

• Basic principles of immunochemical methods
• Reduction of false results and improvement of patient's care and patient's safety
• Practical information for laboratory professionals, clinical chemists

✦ Table of Contents

Contents
Preface
Abbreviations
Part I – Immunoassay: Theory, practice, and patient safety
1 Immunochemical methods – Basic principles and definitions
1.1 Antibody as immunoassay reagent
1.2 Antigen as immunoassay reagent
1.3 The course of the immunochemical reaction
1.4 Immunoassay formats
1.5 Labels in immunochemical reactions
1.6 Separation of bound and unbound fractions
1.7 Other technologies based on the antigen-antibody reaction
1.8 Basic theory of immunoassay and patient safety
2 Immunoassay standardization
2.1 Reference materials for small molecules
2.2 Reference materials for proteins
2.3 Reference methods
2.4 Reference methods for heterogeneous proteins
2.5 Traceability
2.6 The uncertainty of measurement
2.7 Epitope as a solution for better standardization
2.8 Harmonization of immunoassays
2.9 Immunoassay standardization and the patient’s safety
3 Immunoassay calibration and calibration curve fitting
3.1 Calibration process
3.2 Commutability problem
3.3 Matrix effect
3.4 Calibration and patient safety
4 Reference intervals and immunoassay
4.1 General problems with reference intervals for analytes measured by immunoassay
4.2 Limitation of different approaches to reference intervals
4.3 Reference intervals and patient safety
5 Laboratory preanalytical and analytical phase of immunoassay
5.1 Laboratory preanalytical factors and immunoassay
5.2 Blood collection devices
5.3 Anticoagulants
5.4 Hemolysis, lipemia, hyperbilirubinemia, paraproteinemia, and immunoassay
5.5 Analyte stability in fresh and frozen serum samples
5.6 Analytical phase in immunoassay measurement
6 Human natural antibodies and immunoassay
6.1 The human immune system
6.2 Chemical structure of immunoglobulins
6.3 Antigen-combining site and complementarity-determining regions
6.4 Genes for immunoglobulin variable regions
6.5 Diversification of immunoglobulins in vivo
6.6 Natural antibody against exogenous (nonself ) and endogenous (self ) antigens
6.7 Natural antibodies and patient safety
7 Immunoassay interference – How to recognize, eliminate, or reduce it
7.1 Definition and prevalence of interference in immunoassay
7.2 Cross-reactivity versus interference in immunoassay
7.3 Analyte specific and nonspecific binding proteins as a source of interference in immunoassay
7.4 Autoantibodies as a source of interference
7.5 Nonimmune IgG complexes as a source of interference
7.6 Interference from heterophilic antibodies
7.7 Detection of heterophilic antibodies in the patient’s sample
7.8 Methods used for removal or inactivation of interfering heterophilic antibodies
7.9 High-dose effect (hook effect, prozone effect)
7.10 Low-dose hook effect
7.11 Interference from heterophilic antibodies and patient safety
7.12 Interpretation of immunoassay results is an art
8 Immunoassay and patient safety
8.1 Fallibility of immunoassays
8.2 Know your immunoassay
8.3 Basic knowledge on critical points in immunoassay for physicians
8.4 Immunoassay in research
8.5 Who is responsible for the patient’s safety?
Part II – Immunochemistry measurements in practice: Examples of problems in some current immunoassays
Example 1 Parathyroid hormone (PTH) – Heterogeneity as a major problem in PTH measurement by immunochemistry
Example 2 Human chorionic gonadotropin (hCG) – Problems of heterogeneity and lack of standardization
Example 3 Troponin measurement by immunoassay – Problem of low assay sensitivity and interference from heterophilic antibodies
Example 4 Aldosterone and proteolytic renin activity (PRA) – Are they useful together?
Example 5 Thyroglobulin measurement – Autoantibody problem
Example 6 Prolactin measurement by immunoassay – Heterogeneity and macroform problems
Example 7 Thyroid function tests – Most frequently measured and most difficult to interpret: Reference interval for thyroid-stimulating hormone (TSH) and problems of free thyroid hormone fraction measurement
Index