Multiparametric Serological Testing Aids Diagnosis of Autoimmune Encephalitis

Particularly in unexplained neurological cases, a comprehensive autoantibody screening can help to establish a diagnosis, enabling rapid commencement of life-saving therapy. Since many of the autoantibody markers are rare, multiparametric screening composed of different transfected-cell substrates is recommended to increase the diagnostic detection rate.

Scientists at the Institute for Experimental Immunology (Euroimmun AG, Lübeck, Germany) tested a cohort that consisted of 2,716 serum samples received between October and December 2010. The samples were tested on a biochip mosaic combining different neuronal tissue sections with monospecific cell substrates for the detection of antibodies against NMDA receptor (NR1), AMPA receptor (GluR1/GluR2), GABAB receptor, LGI1, CASPR2, GAD65, AQP4, and GlyR.

The team found anti-neuronal immunoglobulin G (IgG) in 108 samples with anti-NMDA receptor antibodies being by far the most prevalent finding (38%), followed by anti-LGI1 (11%) and anti-CASPR2 antibodies (11%). In total, more than 60% of the samples were positive for autoantibodies against neuronal surface antigens, while autoantibodies against classical paraneoplastic intracellular antigens were detected in 31%. The high prevalence of autoantibodies against cell surface antigens in CNS underscores the rising relevance of this novel class of neuronal antigens for autoimmune encephalitis diagnostics.

The evaluation of anti-neuronal autoantibodies was then automated using a new function of the established EUROPattern system. The software automatically takes digital images of the substrates and provides a positive/negative classification. The high-resolution images are sharply focussed with the aid of a counterstain, which also serves to verify correct performance of the incubation. The high-quality of the images was verified by comparing on-screen appraisal with visual microscopy using 753 incubations of numerous serum samples sent to a clinical immunology laboratory.

The two evaluation strategies revealed a concordance of 100% with respect to positive/negative discrimination (excluding samples with ambiguous signals at the microscope to avoid inter-reader deviations). The computer-aided immunofluorescence microscopy considerably facilitates the microscopic analysis, supporting laboratory personnel in the rapid issuance of diagnostic findings. This confirmed the high quality of the images and proves that on-screen evaluation offers a satisfying diagnostic accuracy which can compete with classical immunofluorescence microscopy. The study was published originally published on line on August 1, 2016, in the journal Autoimmunity Reviews.

Related Links:
Euroimmun