Entfällt: Problems in standardizing autoimmune diagnostics and potential solutions using the example of ANA and SmD antibodies in SLE diagnostics
The problems in standardizing immunological tests are mainly based on the individuality of the immune system of the patient and the variability of antigen presentation in different tests. The individual way the immune system recognizes antigens partly depends on its previous encounters with similar antigens, a phenomenon that is called “original antigenic sin”. On the antigen selection and presentation side in the test, variabilities might be based on the particular expression system used, the glycosylation status of the antigens, the 3D structure of the antigens, and the accessibility of hidden epitopes, as e.g. with anti-b2-GPI antibodies. A third variability might come from the different avidities of the detected antibodies, dependent on the detection system, that may correlate with different clinical phenomena as e.g. seen with anti-dsDNA antibodies. Furthermore, the characteristics of the relation between a biomarker and a clinical diagnosis, like sensitivity and specificity, might depend on the prevalence of the underlying cause responsible for the biomarker on one side and for the disease on the other side.
Due to these standardization difficulties results from different test systems and therefore their clinical relevance cannot be directly compared. One way to improve the situation is to calculate the likelihood ratio of a particular result of a particular test that gives the relation between the occurrence of the result in patients versus controls and with it its diagnostic relevance.