Abstract
ObjectiveTo determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions.MethodsEarliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters.ResultsPositive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention.ConclusionsThis novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.
Highlights
Neural immunoglobulin G (IgG) autoantibodies help to define or refine the diagnosis of autoimmune diseases of the central and peripheral nervous system (CNS, PNS) [19, 20, 24, 35]
Much autoantibody testing in the world is done by diagnostic laboratories that investigate material from poorly selected patients, must rely on what is sent in, utilize ready-to-use assays, and are expected to provide test results within a short timeframe
We considered them as “major antibody groups”, given their frequency in the literature [12] and in this study
Summary
Neural immunoglobulin G (IgG) autoantibodies help to define or refine the diagnosis of autoimmune diseases of the central and peripheral nervous system (CNS, PNS) [19, 20, 24, 35]. These antibodies provide an understanding of Romana Höftberger and Theodor W. The added value of data from such a laboratory that it is closely connected to its clinical senders may be a “real-world” impression of frequencies, clinical correlates, and therapeutic and prognostic implications of neural antibodies.
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