Anti-neuronal anti-bodies in patients with early psychosis

Abstract

It may be challenging to distinguish autoimmune encephalitis associated with anti-neuronal autoantibodies from primary psychiatric disorders. Here, serum was drawn from patients with a first-episode psychosis (n=70) or a clinical high-risk for psychosis (n=6) and controls (n=34). We investigated the serum prevalence of 24 anti-neuronal autoantibodies: IgG antibodies for anti-N-methyl-d-aspartate-type glutamate receptor (anti-NMDAR), glutamate and γ-aminobutyric acid alpha and beta receptors (GABA-a, GABA-b), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA), glycine receptor (GlyR), metabotropic glutamate receptor 1 and 5 (mGluR1, mGluR5), anti-Tr/Delta/notch-like epidermal growth factor-related receptor (DNER), contactin-associated protein-like 2 (CASPR2), myelin oligodendrocyte glycoprotein (MOG), glutamic acid decarboxylase-65 (GAD65), collapsin response mediator protein 5/crossveinless-2 (CV2), aquaporin-4 (AQP4), anti-dipeptidyl-peptidase-like protein-6 (DPPX), type 1 anti-neuronal nuclear antibody (ANNA-1, Hu), Ri, Yo, IgLON5, Ma2, zinc finger protein 4 (ZIC4), Rho GTPase-activating protein 26, amphiphysin, and recoverin, as well as IgA and IgM for dopamine-2-receptor (DRD2). Anti-NMDA IgG antibodies were positive with serum titer 1:320 in one patient with a clinical high risk for psychosis. He did not receive a diagnosis of encephalitis after comprehensive neurological evaluation. All other antineuronal autoantibodies were negative and there were no additional findings with immunohistochemistry of brain issues.

Clinically Relevant Anti-Neuronal Cell Surface Antibodies in Schizophrenia Spectrum Disorders

“…Of the seven positive studies, four used a commercially available fixed cell-based assay (CBA) [10-12, 16], two used a live CBA [13, 15], and one used both, as well as a single molecule-based imaging method, for the sake of comparing approaches [14]. The majority of negative studies also used the same aforementioned commercially available CBA (or a modification of it) [17-22, 24-29], and four of these studies also included immunohistochemistry for further testing [19, 26-28]. Two negative studies, including one previously referenced study that also used the commercial CBA kit for testing some of its sample, used in-house CBAs [22, 23].…”

“…Results have been less compelling for anti-AMPAR antibodies, as the majority of studies have been negative [10, 15, 18, 20, 23, 26, 28, 29]. Moreover, in each of the two positive studies, antibodies were found in only one patient (<1% of the samples) [11, 24], and the only study that included a healthy control group also found antibodies in 0.2% of controls [11].…”

“…A number of studies that tested for IgG, IgA, or IgM anti-CASPR2 antibodies found seropositivity in a small percentage (2.5% or less) of patients [11, 15, 24, 29, 36], although numerous other studies were negative [16, 18, 20, 26, 28]. Of note, all of the positive studies that included a healthy control group, however, also found antibodies in a small number of controls (up to 2.9%), and no group differences were found [11, 15, 36].…”

“…All six studies that have screened for antibodies against GABA B R have been negative [11, 18, 24, 26, 28, 29]. …”

“…While one study was negative [28], the other study found only one positive case in both the schizophrenia group as well as the healthy control group [11]. In both groups this represented less than 0.1% of the individuals tested.…”