Routine diagnostics for neural antibodies, clinical correlates, treatment and functional outcome

Abstract

Objective To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions. Methods Earliest 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. Results Positive 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. Conclusions This 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.

Clinical Characteristics and Outcome of Neuronal Surface Antibody-Mediated Autoimmune Encephalitis Patients in a National Cohort

“…In accordance with previous publications of other series (6,(16)(17)(18), the most common autoimmune encephalitis type was anti-NMDAR encephalitis, followed by anti-LGI1 encephalitis (3,19,20). The study by Bien et al (21) reported 576 antibodypositive patients during testing of 10,919 patients for a broad panel of neural antibodies, including onconeural and neuronal cell surface autoantibodies. Our previous study (10) included results of 60 neuronal cell surface autoantibody positive patients (anti-NMDAR, anti-LGI1, anti-GABABR, anti-Caspr2, anti-AMPAR1, 2) and our recent study exclusively included both serologically (neuronal cell surface antibody positive, but not onconeural autoantibody positive) and clinically positive definite AE patients.…”

Seizures associated with antibodies against cell surface antigens are acute symptomatic and not indicative of epilepsy: insights from long-term data

“…Antibodies and their titers (multiples of 1:2) were determined in the Bethel Antibody Laboratory and (since 2016) in the Laboratory Krone, as described previously [2,4]. Ma2 titers were determined with the tissue-based assay [2,4].…”

Neural Autoantibodies in Cerebrospinal Fluid and Serum in Clinical High Risk for Psychosis, First-Episode Psychosis, and Healthy Volunteers

“…While some experts feel confident in diagnosing "autoimmune psychosis" based on serum antibody results (5,13), others keep asking for CSF results-some for concern of specificity of serum-only findings (14), others because antibodies might be hidden in CSF and might go undetected by testing serum only-which is a variant of Susannah Cahalan's concern (2). Indeed, CSF-only reactivity has been shown for NMDAR antibodies in 14-28% of cases (15,16).…”