New serological markers for the differential diagnosis of autoimmune limbic encephalitis1)

Abstract

Abstract Recently, several novel autoantibodies have been identified which are closely associated with different subtypes of autoimmune encephalitis. These antibodies are directed against structures located on the neuronal cell surface: glutamate receptors (types NMDA and AMPA), GABAB receptors, as well as the voltage-gated potassium channel-associated proteins LGI1 and CASPR2. They are much more common than the classical paraneoplastic antibodies (anti-Hu, -Yo, -Ri, -Ma, -CV2, -amphiphysin), less frequently associated with a tumor, and the corresponding clinical syndromes respond significantly better to immunotherapy. Monospecific detection of these autoantibodies in the serum or cerebrospinal fluid of patients is primarily performed by indirect immunofluorescence using transfected HEK293 cell lines recombinantly expressing the membrane-associated target antigens. Owing to the symptom overlap of the respective disorders, it is highly appropriate to determine these parameters in parallel for each patient (autoantibody profiles). Early diagnosis (substantially supported by the serological laboratory), the immediate initiation of immunotherapeutic intervention and, in cases of paraneoplastic etiology, tumor resection are crucial for prognosis. In our own investigations, antibodies against glutamate receptors (type NMDA) are most frequently found among the newly identified forms of autoimmune encephalitis, accounting for 42% of cases. In laboratory practice, one-third of positive reactions were caused by an autoantibody whose determination was not requested by the clinician. Considering the urgency for therapeutic measures in positive cases, these findings substantiate the need to implement multiparametric serological test systems in this diagnostic area.