One major goal of proteomics is to detect biomarkers that may serve as diagnostic or prognostic tools. In this way, biomarkers might be used in clinical routine to accelerate diagnosis or to assist treatment decisions. Unfortunately, examples of clinically used biomarkers that were originally detected via proteomics are scarce.

However, in one scientific domain, namely in autoantibody-related autoimmunity, proteomics has led to discoveries of several biomarkers that are applied in clinical routine diagnostics. These biomarkers are autoantibodies that can be found in serum or cerebrospinal fluid, for example. Interestingly, this research domain is underrepresented in the proteomics community.
Here, my goal is to demonstrate and discuss autoantibodies that are used in clinical routine and that have been identified via proteomics tools. The current version of the autoantibody encyclopedia lists 200 known autoantibodies. It is extremely difficult to estimate how many of them are clinically used in routine diagnostics because some autoantibody biomarkers are only applied in a few countries or even hospitals. Hence, in this presentation, I want to focus on autoantibodies used in neurology.

One of the first autoantibodies that were discovered in neurological diseases were paraneoplastic neurological syndromes, i.e., diseases of the nervous system that are secondary to cancer and involve T or B cell-related autoimmunity. Some of the autoantibodies have been identified via proteomics-like methods of the pre-proteomics era.
More recently, important biomarkers have been discovered in demyelinating inflammatory polyneuropathies. The presence of anti-neurofascin or anti-contactin autoantibodies defines the entity of autoimmune nodopathies. Hence, their detection is mandatory for disease diagnosis. Regarding anti-neurofascin antibodies, the corresponding band of interest was detected in 2007 using the isolated glycoprotein fraction from human myelin upon affinity chromatography. The actual protein was identified via 2D gel electrophoresis and detection of the autoimmune targets by incubating the patient serum, followed by mass spectrometry. Anti-contactin autoantibodies have been detected in 2012 via immunoprecipitation of the autoantibody targets, one-dimensional gel separation, and identification of the protein in the additional band via mass spectrometry.

Interestingly, these biomarkers have even changed the clinical perspective towards some diseases leading to entirely novel disease entities. In conclusion, autoantibodies are important diagnostic tools in neurology but also in other clinical domains. Until today, proteomics is a promising tool to discover novel autoantibody biomarkers. The discovery of clinically relevant autoantibodies is one of the forgotten but major success stories of our proteomics community.