DNA hydrolysing IgG catalytic antibodies: an emerging link between psychoses and autoimmunity

Abstract

It is not uncommon to observe autoimmune comorbidities in a significant subset of patients with psychotic disorders, namely schizophrenia (SCZ) and bipolar disorder (BPD). To understand the autoimmune basis, the DNA abyzme activity mediated by serum polyclonal IgG Abs were examined in psychoses patients, quantitatively, by an in-house optimized DNase assay. A similar activity exhibited by IgG Abs from neuropsychiatric-systemic lupus erythematosus (NP-SLE) patients was used as a comparator. Our data revealed that the IgG DNase activity of SCZ was close to that of NP-SLE and it was twofold higher than the healthy controls. Interestingly, the association between DNase activity with PANSS (positive, general and total scores) and MADRS were noted in a subgroup of SCZ and BPD patients, respectively. In our study group, the levels of IL-6 and total IgG in BPD patients were higher than SCZ and healthy controls, indicating a relatively inflammatory nature in BPD, while autoimmune comorbidity was mainly observed in SCZ patients.

Catalytic Antibodies in Bipolar Disorder: Serum IgGs Hydrolyze Myelin Basic Protein

“…A comparison of the level of MBP-hydrolyzing activity in autoimmune and mental disorders showed that the percentage of antibodies with pronounced activity decreases in the following series: MS (84%) < schizophrenia (69%) < BAR (52%) [34,37]. Our results are consistent with the first study of DNA-hydrolyzing IgG in bipolar disorder, which showed a decrease in activity levels compared with patients with schizophrenia and SLE [43]. The differences in the level of proteolytic activity of serum antibodies revealed in this article indirectly indicate differences in the pathogenesis of affective and psychotic disorders, when autoimmunity can be much less pronounced in bipolar disorder than in schizophrenia.…”

“…However, these results are consistent with data on DNA-binding and DNA-hydrolyzing IgGs in BD. Ramesh R. et al showed that the DNA-hydrolyzing activity of antibodies is increased in patients with bipolar disorder compared to healthy individuals, but the titers of antibodies to DNA are even lower than in healthy subjects [43].…”

“…The first work on the study of catalytic antibodies in bipolar disorder appeared in 2021, indicating the presence of DNA-hydrolyzing activity of serum IgG [43]. However, antibodies with proteolytic activity against neurogenic proteins, such as myelin basic protein (MBP), have not been previously studied in patients with BD.…”

The Influence of Antipsychotic Treatment on the Activity of Abzymes Targeting Myelin and Levels of Inflammation Markers in Patients with Schizophrenia

“…Among antigen-binding antibodies there are antibodies that can catalytically modify the antigen. Such antibodies have been identified in various mental disorders [ 25 , 26 ]. In patients with schizophrenia, catalytic antibodies (abzymes) hydrolyzing DNA [ 27 ], RNA, and miRNA [ 28 ], histones [ 29 ], and myelin basic protein (MBP) [ 20 , 30 ] have been previously found.…”

Оценка цитотоксических эффектов IgG, выделенных из сыворотки крови больных шизофренией

“…В последние годы в сыворотке крови пациентов, страдающих шизофренией, обнаружены антитела, обладающие каталитическими свойствами (абзимы). К настоящему времени выявлены следующие абзимы: ДНК, РНК, ОБМ и гистон-гидролизующие и расщепляющие гидроперекись водорода иммуноглобулины класса G (IgG) [7,8,9]. Вместе с тем биологическая роль абзимов в патогенезе заболевания не изучена всесторонне и не установлена окончательно.…”