Article

ISSN 0006-2979, Biochemistry (Moscow), 2026, Vol. 91, No. 6, pp. 1023-1033 © The Author(s), 2026. This article is an open access publication.

1023

Hydrogen Peroxide Dismutation by Immunoglobulins G

from Patients with Schizophrenia

Daria V. Kazantseva

, Liudmila P. Smirnova

1,a

*, Elena G. Kornetova

and Svetlana A. Ivanova

Mental Health Research Institute, Tomsk National Research Medical Center, 634014 Tomsk, Russia

e-mail: lpsmirnova2016@gmail.com

Received February 19, 2026

Revised June 15, 2026

Accepted June 16, 2026

Abstract— The mechanisms underlying the recently discovered catalase activity of immunoglobulin  G (IgG)

in patients with schizophrenia remain unclear. Using a series of rigorous criteria, it has been demonstrated

that this activity is an intrinsic property of antibodies themselves. The present study shows that classi-

cal catalase inhibitors also suppress the catalase activity of IgG. Specifically, inhibitor analysis revealed a

dose-dependent reduction in the IgG catalase activity following addition of sodium azide (IC

  =  140  μM) and

3-aminotriazole (IC

  =  16.06  μM), suggesting that the catalytic mechanism of IgG shares similarities with

that of classical catalase and may be due to the ability of antibodies to bind metalloporphyrin complex-

es, including heme. IgG catalase activity in patients with schizophrenia during therapeutic remission was

significantly reduced, being fourfold lower than in healthy controls (p  =  0.0004) and twofold lower than

in patients during disease exacerbation (p  =  0.002). A moderate positive correlation was observed between

the total Positive and Negative Syndrome Scale (PANSS) score and IgG catalase activity (R  =  0.32, p  =  0.01).

Therefore, IgG catalase activity in patients with schizophrenia depends on the disease clinical state and

may contribute to the regulation of reactive oxygen species (ROS) metabolism and the severity of oxidative

stress in affected individuals.

DOI: 10.1134/S0006297926600456

Keywords: catalase activity of IgG, abzymes, oxidative stress, schizophrenia

* To whom correspondence should be addressed.

INTRODUCTION

Schizophrenia is one of the most severe mental

disorders, affecting approximately 23.6 million peo-

ple worldwide  [1]. It is a progressive mental illness

characterized by a heterogeneous spectrum of poly-

morphic symptoms, that results in persistent impair-

ment of social functioning and requires long-term

treatment, thus imposing a substantial social and

economic burden on society  [2].

Oxidative stress plays a significant role in the

pathogenesis of schizophrenia due to imbalance be-

tween pro-oxidant processes and antioxidant de-

fense, both at the early and chronic stages of the

disease  [3,  4]. This redox imbalance leads to several

molecular abnormalities, including dysfunction of

redox-sensitive transcription factors such as nuclear

factor erythroid 2–related factor 2 (Nrf2) and nuclear

factor kappa  B (NF-κB), mitochondrial insufficiency,

and selective damage to GABAergic (γ-aminobutyric

acid-ergic) interneurons, which ultimately plays a

role in the formation of clinical symptomatology in

schizophrenia  [3]. Oxidative stress occurs when the

generation of reactive oxygen species (ROS) exceeds

the capacity of cellular antioxidant systems to neu-

tralize them  [5]. ROS are highly reactive molecules

capable of interacting with various cellular compo-

nents, causing their structural and functional damage.

However, at controlled physiological concentrations,

ROS serve as essential signaling molecules involved

in the regulation of numerous intracellular signaling

pathways and synaptic functions [6,  7].

As oxidants, ROS can damage nucleic acids

by inducing modifications into DNA bases and the

KAZANTSEVA et al.1024

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

sugar-phosphate backbone, as well as by causing sin-

gle- and double-strand breaks and the formation of

DNA–DNA and DNA–protein crosslinks  [8]. ROS-me-

diated protein oxidation results in the generation

of carbonyl groups on the side chains of amino

acid residues such as lysine, arginine, proline, and

threonine. In addition, secondary lipid peroxidation

products, including malondialdehyde (MDA) and 4-hy-

droxy-2-nonenal (4-HNE), promote the formation of

intra- and intermolecular protein crosslinks, further

impairing various cellular function [9, 10].

The nervous system is particularly susceptible to

oxidative damage due to several intrinsic character-

istics. First, the brain has a high demand for oxygen

and relies heavily on aerobic metabolism (oxidative

phosphorylation) for energy production  [11]. Second,

neuronal membranes are enriched in polyunsaturat-

ed fatty acids (PUFAs), which are highly vulnerable

to lipid peroxidation  [12]. Third, brain tissue contains

significant concentrations of transition metals, espe-

cially iron and copper, which can catalyze ROS gen-

eration through redox reactions  [13]. Furthermore,

free radicals participate in normal neuroregulatory

processes  [14], and certain neurotransmitters and

hormones can themselves generate ROS [15-17].

Antipsychotic medications, the mainstay of long-

term schizophrenia treatment, may contribute to the

development of oxidative stress [3, 18-20]. Typical an-

tipsychotics appear to disrupt redox homeostasis to a

greater extent than atypical agents [21]. Nevertheless,

prolonged antipsychotic therapy is associated with

increased systemic oxidative stress regardless of the

specific class of antipsychotic used [19, 22].

Abzymes (catalytic antibodies) are immunoglobu-

lins that possess catalytic activity  [23]. Immunoglobu-

lin  G (IgG) has been shown to catalyze a wide range

of reactions, including the hydrolysis of DNA, RNA,

proteins, and oligosaccharides, as well as oxidoreduc-

tase reactions, such as the dismutation of superoxide,

hydrogen peroxide, and peroxidase reactions. Rela-

tively recently, catalase activity has been identified in

IgG from patients with schizophrenia [24,  25], peroxi-

dase activity has been described in healthy individu-

als [26,  27], while superoxide dismutase (SOD) activity

has been reported in patients with multiple sclerosis

and schizophrenia [28,  29]. These oxidoreductase ac-

tivities of polyclonal IgGs presumably contribute to

the neutralization of excess ROS under conditions of

oxidative stress. However, the physiological sites of

action of these antibodies are poorly understood. In

schizophrenia, both blood–brain barrier (BBB) dys-

function  [30] and systemic oxidative stress are well

documented, suggesting potential opportunities for

IgG-mediated antioxidant effects. The mechanisms of

the oxidoreductase activity of IgGs also remain un-

clear.

IgG molecules possess a remarkable capacity to

bind a variety of low-molecular-weight ligands, in

particular heme and transition metal ions, thereby

expanding their functional repertoire. It has been

shown that heme acts as a cofactor of antibodies, con-

ferring catalytic oxidoreductase activity and broaden-

ing their effector functions  [31]. Furthermore, inter-

actions with transition metal ions, heme, and ROS

under oxidative stress conditions can substantially

modulate the antigen-binding and catalytic properties

of IgGs [32,  33]. Notably, a high affinity for the heme

is frequently associated with antibody polyreactivity,

due to the structural features of their complementar-

ity-determining regions (CDRs)  [34].

The present study continues investigation of the

IgG catalase activity in patients with schizophrenia.

To date, the relationship between the catalase activity

of antibodies and clinical features of schizophrenia

has not been examined. Elucidating this association

may provide new insights into the role of antibod-

ies with the catalase activity in the pathogenesis of

this disease. In addition, a comprehensive inhibitor

analysis was performed to explore potential molecu-

lar mechanisms underlying the catalase-like activity

of IgGs.

MATERIALS AND METHODS

Characteristics of study participants. The study

was conducted at the Laboratory of Molecular Genet-

ics and Biochemistry of the Mental Health Research

Institute, Tomsk National Research Medical Center.

Clinical verification of schizophrenia diagnoses was

performed by psychiatrists from the Department of

Endogenous Disorders of the same institution. Diagno-

ses were confirmed based on ICD-10 criteria and sup-

ported by the assessment of symptom severity using

the Positive and Negative Syndrome Scale (PANSS).

A total of 124 individuals were examined, in-

cluding 82 patients (52 men, 30 women) diagnosed

with paranoid schizophrenia (ICD code F20.0) who

were receiving treatment at the institute’s clinics.

The mean age of patients was 33.6  ±  5.12 years, and

the mean disease duration was 8.9  ±  4.62 years. The

median total PANSS score in the overall schizophre-

nia group was 96 [87; 106]. The patients were divid-

ed into two groups: 42  inpatients experiencing an

acute exacerbation of the disease and 40 outpatients

in therapeutic remission. Patients in therapeutic re-

mission were receiving maintenance therapy with

atypical antipsychotic medications, most commonly,

risperidone, quetiapine, or olanzapine.

Inclusion criteria for patients with schizophre-

nia were: (1)  diagnosis of schizophrenia (ICD-10

code F20.0) established by a psychiatrist according

CATALASE ACTIVITY OF IgG IN SCHIZOPHRENIA 1025

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

to ICD-10 criteria; (2)  age between 18 and 60 years;

and (3)  provision of written informed consent for

participation in the study. Exclusion criteria were:

(1)  acute infectious, inflammatory, autoimmune, or

allergic disease; (2)  the presence of any other psychi-

atric disorder not included in the study; (3)  age over

60 years; and (4)  refusal or inability to provide in-

formed consent.

The control group consisted of 42 healthy vol-

unteers (25 men and 17 women) matched to the

schizophrenia group by age and sex. The mean age

of the control participants was 31.6  ±  7.2 years. In-

clusion criteria for the control group were: (1)  age

between 20 and 60 years; (2)  absence of psychiatric

and somatic disorders; and (3)  provision of written

informed consent. Exclusion criteria were: (1)  age

over 60  years; (2)  the presence of psychiatric disor-

ders or somatic diseases, including acute or chronic

infectious, inflammatory, and autoimmune conditions;

and (3)  refusal to participate in the study.

Study material. Peripheral blood serum samples

were obtained from patients with schizophrenia and

healthy controls. Venous blood was collected from the

ulnar vein in the morning after an overnight fast,

upon admission to the clinic and prior to the initi-

ation of therapy. Blood samples were collected into

Vacuette tubes containing a clot activator. To separate

serum from blood cells, the samples were centrifuged

at 2000g for 20  min in a refrigerated centrifuge (Orto

Alresa Digicen 21R, Spain). Following centrifugation,

the serum was aliquoted into Eppendorf tubes and

stored at −80°C until further analysis.

Isolation of antibodies from blood serum by

affinity chromatography on Protein G-Sepharose.

Blood serum from patients and healthy individuals

(500  μL) was thawed, diluted to a final volume of

2  mL with Buffer  A (50  mM Tris-HCl, pH  7.5; 150  mM

NaCl) and applied on a Protein G-Sepharose column

equilibrated with the same buffer. Unbound proteins

were washed out with Buffer A until the absorbance

at 280  nm returned to baseline. Non-specifically

bound proteins and lipids were eluted with Buffer  A

containing 1%  Triton X-100. IgGs were then eluted

with 100  mM glycine-HCl (pH  2.6); collected fractions

were immediately neutralized with 1  M Tris-HCl

(pH  8.5).

Dialysis of IgG preparations was performed

to remove low-molecular-weight impurities and ex-

change the elution buffer for the working solution.

Immediately before the procedure, dialysis bags were

boiled in deionized water. The antibody preparations

were then transferred into dialysis bags and dialyzed

against 20 mM sodium phosphate buffer (pH  7.0)

at 4°C for 17  h.

Determination of protein concentration. Pro-

tein concentration in the obtained preparations was

determined spectrophotometrically from the absor-

bance at 280 and 260  nm using a Varioskan LUX

spectrophotometer (Thermo Fisher Scientific, USA)

at the Medical Genomics Shared Research Facility

(Tomsk National Research Medical Center).

Electrophoretic analysis of antibody homoge-

neity. IgG preparations were fractionated by sodium

dodecyl sulfate–polyacrylamide gel electrophoresis

(SDS–PAGE) in 4-18% gradient polyacrylamide gels

according to the Laemmli’s method (1970). Protein

samples were mixed with a loading buffer contain-

ing Bromophenol blue, heated at 100°C for 1  min,

and loaded onto a gel (10  μg per lane). Electropho-

resis was performed at 180  V. Following separation,

proteins were stained with Coomassie Brilliant Blue

R-250 and the gels were visualized using an iBright

FL1500 Imaging System (Thermo Fisher Scientific) at

the Medical Genomics Shared Research Facility from

Tomsk NRMC.

Gel filtration of IgGs under pH shock condi-

tions. Combined IgG preparations (1.8  mL, 6.1  mg/mL)

were diluted 10-fold with 1  M glycine-HCl buffer

(pH  2.6) and incubated for 30  min at room tempera-

ture. Next, gel filtration was performed on a Super-

dex-200 HR 10/30 column equilibrated with 50  mM

glycine-HCl (pH  2.6) containing 0.3  M  NaCl. Proteins

were eluted with the same buffer at a flow rate of

0.2  mL/min; collected fractions were immediately

neutralized with 1  M Na-phosphate buffer, pH  8.4.

IgG catalase activity assay. Catalase activity of

IgG preparations was measured spectrophotomet-

rically using a Cary 60 UV–Vis spectrophotometer

(Agilent Technologies, USA) equipped with a Kinetics

module based on the decrease in hydrogen peroxide

concentration upon antibody addition. The reaction

mixture contained 15  mM H

in 50  mM phosphate

buffer (pH  7.0) and 100  μL of antibody solution (0.1-

0.5  mg/mL). Changes in absorbance at 240  nm were

recorded for 5  min, and catalase activity was cal-

culated using the millimolar extinction coefficient

of hydrogen peroxide (ε240  =  0.081  mM

−1

·cm

−1

) and

expressed as activity units  (U), where one unit cor-

responds to the decomposition of 1  μmol  H

per

minute, per mg IgG (μmol H

·min

−1

·mg

−1

  IgG).

Inhibitor analysis. To investigate the catalytic

mechanism of IgG preparations, inhibitory analysis

was performed using 3-amino-1,2,4-triazole (3-AT)

and sodium azide (NaN

). Experiments were con-

ducted using independent IgG preparations obtained

from patients with schizophrenia and healthy con-

trols (n  =  5 in each group). 3-AT, a classical catalase

inhibitor that covalently modifies histidine residues

in the catalase active site, was tested at the final con-

centrations of 10, 20, 25, and 50  μM. Sodium azide, an

non-specific inhibitor of metal-dependent catalytic ac-

tivity that binds transition metal ions (Cu

and Fe

KAZANTSEVA et al.1026

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

Fig.  1. Representative affinity chromatogram of IgG isolation from the blood of a patient with schizophrenia on Protein G–

Sepharose: peak  1, flowthrough; peak 2, lipids and non-specifically bound proteins eluted with Triton X-100; peak 3, IgG;

mAU, milli-absorbance units (1  mAU = 0.001  AU).

was added to IgG samples at the final concentrations

of 0.005, 0.01, 0.025, 0.05, 0.25, 0.5, and 1.0  mM and

incubated for 20  min. Catalase activity measured in

the absence of inhibitors was taken as 100%, and all

results were expressed as a percentage of this control

activity. The half-maximal inhibitory concentration

was determined using the Very Simple (IC

) Tool Kit

online software with the GNUPLOT package. Mean ac-

tivity values were used for curve fitting, and IC

val-

ues were calculated by the least-squares regression of

the inhibitory curves.

Statistical analysis of the obtained data was car-

ried out using Statistica  12.0 software. Since the data

did not follow a normal distribution, the non-para-

metric Kruskal–Wallis and Mann–Whitney U  tests

were used. Correlation analysis was performed using

the Spearman rank correlation coefficient. Differenc-

es were considered significant at p  <  0.05.

RESULTS

To investigate the catalytic activity of antibodies,

it is essential to first demonstrate that the observed

activity belongs to antibodies themselves and not to

co-purified enzymes. To reliably attribute catalytic

activity to antibodies, a set of stringent criteria has

been established  [35]. Previous studies have shown

that fulfillment of three key criteria is sufficient

to confirm the antibody origin of catalytic activity.

In the present study, the following criteria were ap-

plied: isolation of IgG using an affinity sorbent; veri-

fication of homogeneity of purified antibody prepara-

tions by electrophoresis in a gradient polyacrylamide

gel; retention of catalytic activity following gel filtra-

tion under pH shock conditions.

IgGs were isolated from individual blood serum

samples of patients with schizophrenia and healthy

donors using affinity chromatography on Protein

G-Sepharose. It has been previously shown that this

method yields homogeneous IgG preparations free of

contaminating serum proteins  [36]. Protein  G has a

high affinity for the Fc regions of all IgG subclass-

es except IgG3, enabling selective removal of com-

ponents of immune complex, including proteins,

polysaccharides, and nucleic acids, using high ionic

strength or nonionic detergents. These conditions

preserve the interaction between IgG and protein  G

while effectively disrupting nonspecific noncovalent

immune complexes.

All polyclonal IgG preparations obtained from

both patients with schizophrenia and healthy individ-

uals exhibited similar chromatographic profiles and

were eluted with acidic buffer (pH  2.6) as a single

sharp peak (Fig.  1, peak  3). Protein fractions corre-

sponding to the peak central portion were collected,

pooled, and used for subsequent analysis.

During the isolation process, antibody prepara-

tions were subjected to the acid shock (pH  2.6), which

usually leads to the loss of catalytic activity of en-

zymes, including abzymes. The recovery of catalytic

activity is typically observed after abzyme prepara-

tions are stored in a neutral buffer at 4°C for 2-3

weeks due to gradual restoration of immunoglobulin

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BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

Fig.  2. Analysis of homogeneity of IgG preparations by

SDS-PAGE in 4-18% polyacrylamide gel stained with

Coomassie Brilliant Blue R-250. Lanes1-5)IgGs from patients

with schizophrenia (150-kDa band); M) molecular weight

protein marker (kDa).

native conformation. However, storing antibodies un-

der non-physiological conditions often leads to their

precipitation. For this reason, purified IgG samples

were dialyzed against 20  mM sodium phosphate buf-

fer (pH  7.0), which stabilized the antibody solutions.

The homogeneity of antibody preparations was

assessed by non-reducing SDS-PAGE that revealed a

single predominant protein band at approximately

150  kDa, corresponding to IgG (Fig.  2). Electrophoret-

ic homogeneity of antibody preparations is one of the

criteria supporting attribution of catalytic activity to

the studied IgG.

Gel filtration is among the most stringent ap-

proaches for attributing catalytic activity to anti-

bodies. Using acidic conditions ensures disruption

of non-covalent interactions and dissociation of all

components of immune complexes composed of im-

munoglobulins of different classes and associated

antigens. Three electrophoretically homogeneous IgG

preparations were pooled, preincubated in Tris–gly-

cine buffer (pH  2.6), loaded on a column, and eluted

with the same acidic buffer (acid shock), yielding a

single peak corresponding to IgG. Collected fractions

were assessed for catalase activity, demonstrating

that the elution profile closely matched the distribu-

tion of catalase activity (Fig.  3).

Thus, using a series of generally accepted crite-

ria for attributing catalytic activity to antibodies, we

demonstrated that the observed catalase activity was

an intrinsic property of IgGs.

It was further shown that IgGs from both pa-

tients with schizophrenia and healthy donors ex-

hibited catalase activity, which differed significant-

ly between IgGs from patients during exacerbation

(1739.11 [584.10; 3508.50] U/mg IgG), patients in ther-

apeutic remission (602.45 [0.00; 1624.25] U/mg IgG),

and healthy individuals (2574.74 [1194.45; 4910.21]

U/mg IgG) (p  =  0.0003). Catalase activity in patients

during exacerbation did not differ significantly from

that in healthy individuals (p  =  0.22). In contrast, IgGs

from patients in therapeutic remission exhibited ap-

proximately fourfold lower activity compared with

healthy individuals (p  =  0.0004) and nearly threefold

lower activity compared with patients in the acute

phase (p  =  0.002) (Fig.  4). Amoderate positive correla-

tion was identified between the catalase activity of

IgGs from patients with schizophrenia and the total

PANSS score (R  =  0.32, p  =  0.01).

Inhibitor analysis showed that 3-AT suppressed

the catalytic activity of IgGs in a dose-dependent

manner. The most pronounced effect (complete inhi-

bition) was observed at 50  μM 3-AT, while no inhi-

bition occurred at 10  μM (Fig.  5a). To determine the

inhibitor concentration corresponding to 50% inhibi-

tion, a dose response curve was constructed based on

Fig.  3. Gel filtration of IgG preparations under acid shock conditions and catalase activity in the collected fractions (only

a fragment of chromatogram corresponding to IgG elution is shown). Solid line, IgG concentration; dashed line, catalase

activity, U/mg IgG (μmol H

·min

−1

·mg

−1

  IgG).

KAZANTSEVA et al.1028

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

Fig.  4. IgG catalase activity in patients with schizophrenia during exacerbation (1), patients in therapeutic remission (2),

and healthy individuals (3); p-values were calculated using the Mann–Whitney U  test; *  significant differences.

the obtained data, yielding a classical sigmoidal re-

lationship. The half-maximal inhibitory concentration

(IC

) calculated using the Very Simple IC

Toolkit,

was 16.06  μM (Fig.  5b).

A similar inhibitor analysis was performed using

sodium azide, a non-specific inhibitor of metal-depen-

dent enzymes. Sodium azide also reduced the IgG cat-

alase activity in a dose-dependent manner, although

its inhibitory potency was lower across the tested

concentration range. Complete inhibition of enzymat-

ic activity was observed at 500  μM, whereas no effect

was detected at 5  μM (Fig.  6a). Based on the resulting

dose response curve, the half-maximal inhibitory con-

centration (IC

) was estimated to be 140  μM (Fig.  6b).

DISCUSSION

Numerous studies have demonstrated alterations

in antioxidant defense systems and activation of

pro-oxidant processes in patients with schizophrenia

[3, 4, 37, 38]. Collectively, these findings suggest that

abzymes exhibiting oxidoreductase (antioxidant) ac-

tivity may constitute an important functional compo-

nent of mammalian antioxidant system[3, 39]. Inthe

context of immunological dysregulation[40], humoral

immune activation [41], systemic oxidative stress [3],

and local impairments in the antioxidant defense[42]

observed in schizophrenia, investigating catalytic an-

tibodies with oxidoreductase properties can substan-

tially broaden current understanding of redox alter-

ations in this disorder. At the organismal level, such

antibodies may partially compensate for deficiencies

in canonical antioxidant systems in schizophrenia.

We found no significant differences in the IgG

catalase activity between patients experiencing

schizophrenia exacerbation and healthy controls,

which may reflect relatively low circulating hydro-

gen peroxide levels, as well as broader alterations in

systemic redox regulation in schizophrenia.

By contrast, outpatients in therapeutic remission

receiving antipsychotic treatment exhibited signifi-

cantly reduced IgG catalase activity compared with

both patients in the acute phase of the disease and

healthy controls. This reduction may be associated

with the effects of antipsychotic medications, which

modulate dopaminergic neurotransmission and affect

redox homeostasis. Several atypical antipsychotics

possess intrinsic antioxidant properties and have been

shown to normalize the levels of various pro-oxidant

parameters [43, 44]. Another possible mechanism is

a reduction in hydrogen peroxide production due to

normalization of dopaminergic activity, as dopamine

metabolism via monoamine oxidase is a known source

CATALASE ACTIVITY OF IgG IN SCHIZOPHRENIA 1029

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

Fig.  5. Dependence of catalase activity of IgGs from patients with schizophrenia on 3-AT concentration. a)  Catalase activity

(percentage of activity in the absence of inhibitor taken as 100%); error bars show standard deviation (n  = 5); b) determi-

nation of IC

for  3-AT.

Fig.  6. Dependence of catalase activity of IgGs from patients with schizophrenia on sodium azide concentration. a) Cata-

lase activity (percentage of activity in the absence of inhibitor taken as100%); error bars show standard deviation (n = 5);

b)  determination of IC

for sodium azide.

of H

[15]. Therefore, decreased IgG catalase activi-

ty during remission may indicate not a deterioration

in the antioxidant defense, but rather a restoration

of redox balance and reduced need for compensatory

mechanisms. These findings are consistent with re-

ports of decreased classical erythrocyte catalase activ-

ity in schizophrenia, including a large cross-sectional

study in 2022 reporting its significant reduction (by

28-35%) compared with healthy individuals [45].

A recent study [46] showed that a greater oxi-

dative stress burden, expressed as oxidative stress

index (OSI), and higher concentrations of protein

and lipid oxidation products are associated with a

greater severity of psychopathological symptoms in

schizophrenia, as assessed by the PANSS scale. In our

study, a positive correlation was found between total

PANSS scores and IgG catalase activity, confirming

the assumption that increased IgG catalase activity

may represent a compensatory response to height-

ened oxidative stress.

In order to elucidate the catalytic mechanism of

IgG catalase activity, we studied the effects 3-AT and

sodium azide (classical catalase inhibitors with differ-

ent action mechanisms). Toour knowledge, inhibition

of IgG-associated catalase activity has not been pre-

viously reported. The presence of metal ions bound

KAZANTSEVA et al.1030

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

to immunoglobulin molecules has been demonstrated

by dual-jet plasma atomic emission spectroscopy [26].

The presence of metal ions has also been shown for

IgGs from patients with multiple sclerosis and sys-

temic lupus erythematosus  [47]. Chromatographic

studies using immobilized metal affinity sorbents

have demonstrated that IgG can bind Zn

, Fe

, Cu

, and Co

with high affinity [48]. Thus, immuno-

globulins can adsorb various metals on their surface,

which may explain the dependency of IgG catalase

activity on metals, consistent with its inhibition by

sodium azide, which interacts with Fe

and Cu

[48,

49]. However, the persistence of catalytic activity in

some antibodies after metal chelation indicates the

coexistence of both metal-dependent and metal-inde-

pendent abzyme subpopulations [40].

3-AT is a specific inhibitor of classical catalase,

which covalently binds to the histidine residue in the

enzyme’s active site. 3-AT also inhibited the catalase

activity of IgGs, further supporting the presence of

multiple monoclonal antibody populations with het-

erogeneous catalytic mechanisms within polyclonal

IgG preparations.

The detected catalase activity of IgGs from pa-

tients with schizophrenia may also be due to the

binding of metalloporphyrin complexes, in particu-

lar, heme [31, 32]. The inhibition profile observed in

our study indirectly supports this hypothesis. Sodium

azide is a classical inhibitor of heme-containing en-

zymes, which binds to the iron atom in the porphyrin

ring. Inhibition of IgG activity by 3-AT, which cova-

lently interacts with histidine residues, also perfectly

fits with this hypothesis, as in classical heme pro-

teins, including catalase, it is a histidine residue that

acts as a proximal ligand coordinating the heme iron.

Therefore, it can be assumed that IgG–heme complex-

es may form catalytically active sites functionally

analogous to that in classical catalase, with the iron

atom coordinated by amino acid residues, particular-

ly histidine. Taken together, these results support a

model in which the IgG catalase activity in schizo-

phrenia and in healthy individuals may arise from

a combination of heme-dependent, metal-dependent,

and metal-independent mechanisms

CONCLUSION

This study demonstrates that IgGs from both

patients with schizophrenia and healthy individu-

als exhibits catalase activity, which is an intrinsic

property of antibodies and varies with the clinical

state of the disease. Notably, the catalase activity of

IgGs was significantly reduced in patients in thera-

peutic remission compared with those experiencing

acute disease exacerbation and with healthy controls.

This decrease in the IgG catalase activity in patients

in remission may reflect alterations in the balance

between pro-oxidant and antioxidant processes and

suggests potential implications for therapy adjust-

ment based on the antioxidant status of patients.

Furthermore, the catalase activity of IgGs in pa-

tients with schizophrenia was inhibited by classical

catalase inhibitors, sodium azide and 3-AT, with 3-AT

demonstrating greater potency, as lower concentra-

tions of this compound were required to achieve

maximal inhibition. These findings support a met-

al-dependent catalytic mechanism and suggest that

antibody-mediated catalase-like activity involves an

active site functionally similar to that of the canon-

ical catalase enzyme and presumably contains histi-

dine residues targeted by 3-AT. Overall, the IgG cat-

alase activity in patients with schizophrenia appears

to depend on the disease clinical features and may

contribute to the regulation of ROS metabolism and

the severity of oxidative stress in patients.

Abbreviations

3-AT 3-amino-1,2,4-triazole

half-maximal inhibitory concentration

PANSS positive and negative syndrome scale

ROS reactive oxygen species

Acknowledgments

The study used the equipment from the Medical Ge-

nomics Shared Research Facility, Tomsk National Re-

search Medical Center.

Contributions

L.P.S. and S.A.I. developed the concept and super-

vised the study; E.G.K. verified schizophrenia diagno-

sis in patients and evaluated disease state according

to clinical scales; S.A.I. recruited the control group;

D.V.K. conducted experiments and processed the re-

sults; L.P.S. discussed study results; D.V.K. and L.P.S.

wrote the text of the article; E.G.K. and S.A.I. edited

the manuscript.

Funding

The study was carried out within the framework of

the Fundamental Scientific Research Program “Bio-

psychosocial mechanisms of pathogenesis and clinical

polymorphism, adaptive potential, and predictors of

therapy effectiveness in patients with mental and be-

havioral disorders in the Siberia region”, registration

number 122020200054-8.

Ethics approval and consent to participate

The study was conducted in compliance with the prin-

ciples of the Helsinki Declaration of the World Medi-

cal Association and was approved by the Local Ethics

Committee of the Mental Health Research Institute

CATALASE ACTIVITY OF IgG IN SCHIZOPHRENIA 1031

BIOCHEMISTRY (MOSCOW) Vol. 91 No. 6 2026

(protocol no.157; November18, 2022; no.157/1.2022).

All participants provided written informed consent to

participate in the study.

Conflict of interest

The authors of this work declare that they have no

conflicts of interest.

Open access

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source, provide a link to the Creative Commons li-

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