Anti-Neuronal Autoantibodies (Cell Surface and Onconeural) and Their Association With Natural Autoantibodies in Synthetic Cannabinoid-Induced Psychosis

Abstract

Patients suffering from encephalitis may present psychiatric symptoms; however, the clinical relevance of anti-neuronal antibodies in patients experiencing a psychotic episode without encephalitis is still unclear. In this study, we examined the presence of anti-neuronal cell surface autoantibodies and onconeural autoantibodies in serum samples of 22 synthetic cannabinoid users presenting with psychosis. We found only two positive cases; however, seven patients had borderline results. Nonetheless, we found no significant correlation between anti-neuronal autoantibodies and the intensity of psychosis indicated by the Positive and Negative Syndrome Scale (PANSS) scores. The length of drug use and the combination of other drugs with synthetic cannabinoids have no significant effect on anti-neuronal autoantibody positivity. Nonetheless, the ratio of anti-citrate synthase (anti-CS) IgM and IgG natural autoantibodies was significantly lower (p = 0.036) in the anti-neuronal autoantibody-positive/borderline samples, than in the negative group. Interestingly, anti-CS IgM/IgG showed a significant negative correlation with PANSS-positive score (p = 0.04, r = −0.464). Our results demonstrated that anti-neuronal autoantibody positivity occurs in synthetic cannabinoid users, and the alteration of anti-CS IgM/IgG natural autoantibody levels points to immunological dysfunctions in these cases.

Following Natural Autoantibodies: Further Immunoserological Evidence Regarding Their Silent Plasticity and Engagement in Immune Activation

“…To summarize, herein we present epidemiological and immunoserological data on associations between virus-specific "target" antibodies and "off-target" or "adventitious" nAAbs (Figure 8). Our observations are supplemented by a growing body of literature investigating potential connections between immunization and the concurrent dynamic change in the nAAb repertoire [13][14][15][16][32][33][34][35][36][37]. Based on our current findings, in case of a contemporary antigenic trigger, for SARS-CoV-2 vaccines, in terms of potential associations between virus-specific antibodies and "adventitious" nAAbs, statistically significant associations have been found in connection with the IgG isotype of nAAbs.…”

“…As nAAbs, we used anti-citrate synthase (CS) antibodies; CS is a pacemaker enzyme in the Krebs cycle and is commonly used as a quantitative marker enzyme for the content of intact mitochondria [83,84]. As proven by the scientific literature [21,[32][33][34][35][36][37]46,85,86], CS-specific autoantibodies can be considered a prominent example of nAAbs.…”

“…These antibodies have moderate affinity, are typically poly-reactive, and their levels are physiological and thought to be relatively constant throughout life [9,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. However, in the modern literature, there is increasing evidence of the moderate inducibility of the nAAb repertoire [13][14][15][16][32][33][34][35][36][37].…”

“…IgM isotype nAAbs perform diverse homeostatic functions from injurious to protective, depending on their cellular and molecular environment [41]. Their protective functions, especially, are widely discussed in the scientific literature [10,19,36,[41][42][43]]. Yet, because of their more ancient and conserved origin, levels of IgM isotype nAAbs have been historically considered relatively constant throughout life [21,[44][45][46].…”

Long-Term Course of Neural Autoantibody-Associated Psychiatric Disorders: Retrospective Data from a Specifically Immunopsychiatric Outpatient Clinic

“…Neural autoantibody-associated psychiatric disease is an increasing phenomenon in psychiatry affecting different psychiatric patient groups [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. It is a significant phenomenon associated with approximately 23% of affective disorders [ 16 ], 17% of schizophrenic disorders [ 16 ], and 27% of disorders with cognitive dysfunction [ 13 ].…”