Basic problems of serological laboratory diagnosis.

Serological laboratory diagnosis of infectious diseases is inflicted with several kinds of basic problems. One difficulty relates to the fact that the serological diagnosis of infectious diseases is double indirect: The first indirect aim in diagnosing an infectious disease is to identify the microbial agent that caused the disease. The second indirect aim is to identify this infectious agent by measuring the patient's immune response to the potential agent. Thus, the serological test is neither measuring directly disease nor the cause of the disease, but the patient's immune system. The latter poses another type of problem, because each person's immune system is unique. The immune response to an infectious agent is usually of polyclonal nature, and the exact physicochemical properties of antibodies are unique for each clone of antibody. The clonal makeup and composition and, therefore, the way an individual's immune system sees an infectious agent, depends not only on the genetic background of the person but also on the individual experience from former encounters with various infectious agents. In consequence, the reaction of a patient's serum in an analytical system is not precisely predictable. Also, the antigenic makeup of an infectious agent is not always foreseeable. Antigenic variations leading to different serotypes is a quite common phenomenon. Altogether, these biological problems lead to complexities in selecting the appropriate tests and strategies for testing, in interpreting the results, and in standardizing serological test systems. For that reason, a close collaboration of the laboratory with the clinic is mandatory to avoid erroneous conclusions from serological test results, which might lead to wrong decisions in patient care.