Volume 34, Issue 4

Serological tests for immunoglobulin G 4 (IgG 4 ) against foods are persistently promoted for the diagnosis of food-induced hypersensitivity. Because many patients believe that their symptoms are related to food ingestion without diagnostic confirmation of a causal relationship, tests for food-specific IgG 4 represent a growing market. Testing for blood IgG 4 against different foods is performed with large-scale screening for hundreds of food items by enzyme-linked immunosorbent assay-type and radioallergosorbent-type assays in young children, adolescents and adults. However, many serum samples show positive IgG 4 results without corresponding clinical symptoms. These findings, combined with the lack of convincing evidence for histamine-releasing properties of IgG 4 in humans, and lack of any controlled studies on the diagnostic value of IgG 4 testing in food allergy, do not provide any basis for the hypothesis that food-specific IgG 4 should be attributed with an effector role in food hypersensitivity. In contrast to the disputed beliefs, IgG 4 against foods indicates that the organism has been repeatedly exposed to food components, recognized as foreign proteins by the immune system. Its presence should not be considered as a factor which induces hypersensitivity but rather as an indicator for immunological tolerance, linked to the activity of regulatory T cells. In conclusion, food-specific IgG 4 does not indicate (imminent) food allergy or intolerance but rather a physiological response of the immune system after exposure to food components. Therefore, testing of IgG 4 to foods is considered as irrelevant for the laboratory work-up of food allergy or intolerance and should not be performed in the case of food-related complaints.

This guideline covers all aspects of in vitro allergy diagnostics, including regulation of internal and external quality control, total and allergen specific IgE and IgG antibody measurements, cellular test systems for mast cells, basophils and eosinophils, as well as cellular test systems for T-lymphocytes and inflammatory mediators including ECP (eosinophilic cationic protein), tryptase, histamine and its metabolites. This guideline has already been adopted by several national medical associations.

For more than a century the tuberculin skin test (TST) has been used for the indirect detection of tuberculosis infection. In the past few years, the Interferon-γ-release assays (IGRAs) are available as alternative blood tests for the clinical diagnostic laboratory. The new IGRAs T-SPOT. TB and QuantiFERON-TB Gold in-Tube demonstrate at least comparable sensitivity with a clearly higher specificity than the TST. Compared with the TST, the IGRAs are not confounded by prior BCG vaccination. The IGRAs considerably improve the diagnosis of latent tuberculosis with impact for initiating preventive treatment in contact tracing. Diagnosis of active tuberculosis is still based on microbiological and molecular methods. However, IGRAs can complement the diagnostic methods for pulmonary and extrapulmonary tuberculosis.

The increasing number of β-lactam resistant Gram-negative pathogens is mainly due to production of β-lactamases. Bacteria adapt to newly developed β-lactams by modification of these enzymes or acquisition of new β-lactamases. At present, a large number of different β-lactamases is known exhibiting a diverse spectrum efficacy. Several enzymes are able to hydrolyse modern β-lactams such as carbapenems. Localisation of β-lactamase genes within various mobile genetic elements enables the transfer of resistance within one species or between different Gram-negative species. This results in emergence of multidrug-resistant pathogens whose spectrum of resistance dramatically limits the therapeutic options. Within the scope of the German ARS study (Antibiotic Resistance Surveillance), the Robert Koch Institute Wernigerode investigates β-lactamase production in cephalosporin- and carbapenem-resistant Enterobacteriaceae and Nonfermenters using molecular methods. The aim of this study is the analysis of prevalence and dissemination of relevant β-lactamases as well as identification and surveillance of new β-lactamases or multidrug-resistant nosocomial pathogens.

Research completed during recent years has led to the notion that atherosclerosis is an inflammatory disease. Consequently, highly sensitive assays for C-reactive protein have been used to obtain additional information regarding an individual's cardiovascular risk. However, the measurement of lipoprotein-associated phospholipase A 2 , which specifically reflects the stability of the atherosclerotic plaque, the pathological correlate of atherosclerosis, has not yet been widely used.

There were speculations in the 1960s and 1970s about a compound in human urine which was first named mauve factor and later falsely identified as kryptopyrrole before the correct chemical structure was established as hydroxyhemopyrrollactame. It was thought to be useful in distinguishing a schizophrenic subpopulation. In addition, with certain porphyrias an elevated amount should be found in urine. These speculations were finally disproved in the late 1970s. This substance has now reappeared as hemopyrrollactame and is claimed to produce a severe vitamin B6 and zinc deficiency leading to different illnesses. For testing the substance in urine, expensive and unnecessary laboratory evaluations are proposed as well as nutritional supplements to overcome the deficiency.

Data mining programs help with extracting knowledge from large amounts of data. Despite decades of experience with profile testing, laboratory medicine is just now realizing the practical application of these programs to highly parallel analytical techniques (genomics, proteomics, etc.). Professional data preparation, and most specifically data normalization is crucial for the success of any data mining project. Using routine hospital admission data, we demonstrate how explorative cluster analysis can identify meaningful result patterns. Based upon this feasibility study, the German Association for Clinical Chemistry and Laboratory Medicine is now supporting a research and software development project.