Immune System Dysregulation and Autoimmunity in Schizophrenia: IgGs from Sera of Patients with Several Catalytic Activities

Schizophrenia is usually a progressive mental illness with very different polymorphic symptoms. Several different theories of schizophrenia were discussed; the causes of this disease are not yet clear. Destruction of DNA, RNA, and myelin basic protein (MBP) by inflammation caused by autoimmune reactions has been revealed. Healthy humans usually do not develop abzymes. It was shown that DNase, RNase, and MBP-hydrolyzing abzymes are easily detectable at the beginning of different autoimmune diseases (AIDs). During the development of spontaneous and induced AIDs in mice, a specific reorganization of their immune system associated with the generation of abzymes hydrolyzing different autoantigens was revealed. SCZ is currently not assigned to classical autoimmune diseases. However, the sera of approximately 30% of SCZ patients demonstrated a high level of anti-DNA Abs (comparing to 37% of SLE patients); abzymes hydrolyzing DNA, RNA, and MBP were revealed in 80–100% of SCZ patients. The site-specific hydrolysis of four known SCZ-specific microRNA playing an important role in the regulation of several genes functioning was revealed. Anti-MBP IgGs hydrolyze specifically only MBP but not other proteins. The data indicate that SCZ patients may to a certain extent show similar to SLE and MS patients’ typical signs of autoimmune processes

Human Milk Lactoferrin and Antibodies: Catalytic Activities, Complexes, and Other Features

Human milk is a source of biologically active proteins, including lactoferrin (LF) and antibodies (Abs). These proteins are considered as the most polyfunctional proteins of human milk. Apparently, human milk is not a simple mixture of proteins and peptides: recently it was shown that human milk contains stable supramolecular protein complex, composed of LF, α‐lactalbumin, milk albumin, β‐casein, IgG, and sIgA molecules. We believe that the whole set of different biological functions of the individual milk proteins is significantly supplemented by features of their complexes

IgG antibodies with peroxidase-like activity from the sera of healthy Wistar rats

AbstractVarious catalytic antibodies or abzymes (Abzs) have been detected recently in the sera of patients and animals with many autoimmune diseases, where their presence is most probably associated with autoimmunization. Normal humans or animals usually do not contain Abzs. In contrast, polyclonal Abzs from healthy humans and animals have an intrinsic superoxide dismutase activity and catalyze formation of H2O2 (Wentworth et al., 2000, Proc. Natl. Acad. Sci. USA; 2001, Science). Here, we present the first evidence showing that highly purified native IgGs from the sera of healthy Wistar rats interact with H2O2 and possess peroxidase-like activity. Specific peroxidase activity of IgG preparations from the sera of 10 rats varied in the range 1.6–27% as compared with that for horseradish peroxidase (100%). Antioxidant enzymes such as superoxide dismutases, catalases, and glutathione peroxidases are known to represent critical defence mechanisms for preventing oxidative modifications of DNA, proteins, and lipids. Antioxidant peroxidase activity of Abzs can also play an important role in the protection of organisms from oxidative stress as well as in oxidation of toxic compounds

Climate Change, Growth, and California Wildfire

Large wildfire occurrence and burned area are modeled using hydroclimate and landsurface characteristics under a range of future climate and development scenarios. The range of uncertainty for future wildfire regimes is analyzed over two emissions pathways (the Special Report on Emissions Scenarios [SRES] A2 and B1 scenarios); three global climate models (Centre National de Recherches Météorologiques CM3, Geophysical Fluid Dynamics Laboratory CM21 and National Center for Atmospheric Research PCM2); a mid‐range scenario for future population growth and development footprint; two model specifications related to the uncertainty over the speed and timing with which vegetation characteristics will shift their spatial distributions in response to trends in climate and disturbance; and two thresholds for defining the wildland‐urban interface relative to housing density. Results were assessed for three 30‐year time periods centered on 2020, 2050, and 2085, relative to a 30‐year reference period centered on 1975. Substantial increases in wildfire are anticipated for most scenarios, although the range of outcomes is large and increases with time. The increase in wildfire area burned associated with the higher emissions pathway (SRES A2) is substantial, with increases statewide ranging from 57 percent to 169 percent by 2085, and increases exceeding 100 percent in most of the forest areas of Northern California in every SRES A2 scenario by 2085. The spatial patterns associated with increased fire occurrence vary according to the speed with which the distribution of vegetation types shifts on the landscape in response to climate and disturbance, with greater increases in fire area burned tending to occur in coastal southern California, the Monterey Bay area and northern California Coast ranges in scenarios where vegetation types shift more rapidly.National Oceanic and Atmospheric Administration (NOAA) Regional Integrated Science and Assessment Program for California, United StatesCalifornia Climate Change Center/[CEC-500-2009-046-F]//Estados UnidosUnited States Department of Agriculture (USDA) Forest Service Pacific Southwest Research Station///Estados UnidosNational Oceanic and Atmospheric Administration (NOAA) Regional Integrated Science and Assessment Program for California///Estados UnidosUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI

Клещевой энцефалит: иммунологические показатели возможного перехода острой стадии в хроническое течение болезни

Several autoimmune diseases with chronic clinical course are characterized by detection of DNA autoantibodies in patients’ serum, while there are no such IgGs in healthy donors’ blood or in patients with acute clinical course with no evidence of chronization. Tick-borne encephalitis has not been considered this way. Several strict criteria have been applied to show that the DNase activity is an intrinsic property of IgGs from the sera of TBE patients but not from healthy donors. The relative activity of IgGs has been shown to vary extensively from patient to patient, but most of the preparations (91%) had detectable levels of the DNase activity. Polyclonal DNase IgGs were not active in the presence of EDTA or after a dialysis against EDTA, but could be activated by several externally added metal ions, with the level of activity decreasing in the order Mn2+ + Ca2+ ≥ Mn2+ + Mg2+ ≥ Mn2+ ≥ ≥ Mg2+ + Ca2+ ≥ Ca2+ ≥ Mg2+ > Ca2+, while K+ , Na+ , Ni2+, Zn2+, and Cu2+ did not stimulate DNA hydrolysis. Affinity chromatography on DNA-cellulose separated the DNase IgGs into many subfractions with various affinities for DNA and very different levels of the relative activity. Possible reasons for catalytic diversity of polyclonal human Abzs are discussed.Ряд аутоиммунных заболеваний с хроническим течением характеризуются обнаружением в крови больных ДНКаутоантител, в то время как их не содержит кровь здоровых доноров или пациентов с острым течением заболеваний, незначительным нарушением иммунного статуса, без определенной склонности к переходу в хронический процесс. Клещевой энцефалит (КЭ) не рассматривался с этих позиций. Предварительно для данной работы проведен поиск достаточно точных критериев обнаружения ДНК-активности антител иммуноглобулина (Ig) G из сыворотки крови больных КЭ и здоровых доноров. Показано, что относительная активность антител IgG значительно варьирует у пациентов, но большинство образцов (91%) имели определяемый уровень ДНКазной активности. Поликлональные ДНКазные антитела IgG не активировались в присутствии ЭДТА или после диализа с ЭДТА, но могли активироваться некоторыми добавленными ионами металлов с уровнем активности, уменьшающимся в ряду Mn2+ + Ca2+ ≥ Mn2+ + Mg2+ ≥ Mn2+ ≥ Mg2+ + Ca2+ ≥ Co2+ ≥ Mg2+ > Ca2+, в то время как K+ , Na+ , Ni2+, Zn2+ и Cu2+ не стимулировали гидролиз ДНК. Аффинная хроматография на ДНК-целлюлозе разделила ДНКазные антитела IgG на множество субфракций с различным сродством к ДНК и очень разными уровнями относительной активности. Возможные причины каталитического разнообразия поликлональных человеческих аутоантител обсуждаются

Multiple Sclerosis: Enzymatic Cross Site-Specific Recognition and Hydrolysis of H2A Histone by IgGs against H2A, H1, H2B, H3 Histones, Myelin Basic Protein, and DNA

Histones have a paramount role in chromatin remodeling and gene transcription. Free histones are damage-associated molecules in the blood; administration of histones to animals drives systemic inflammatory and toxic effects. Myelin basic protein (MBP) is the most crucial component of the axon myelin-proteolipid sheath. Antibodies-abzymes with different enzymatic activities are very toxic and an essential feature of some autoimmune diseases. Electrophoretically homogeneous IgGs against H1, H2A, H2B, H3, H4, MBP, and DNA were derived from sera of multiple sclerosis (MS) patients by several affinity chromatographies. Using MALDI-TOFF mass spectrometry, it was shown that IgGs against H2A split H2A at 12 sites; the number of H2A hydrolysis sites by antibodies against other antigens is different: H1 (19), H2B (11), H3 (15), H4 (9), MBP (10), and DNA (23), and they only partly match. Thus, the complex formation polyreactivity and the enzymatic cross-activity of pernicious humans IgGs against five histones, MBP, and DNA have been shown for the first time. The data obtained indicate that the formation of such polyspecific-polyreactive abzymes, whose single active center can recognize and hydrolyze different substrates, can occur due to the formation of antibodies against hybrid antigenic determinants consisting of several histone protein sequences. IgGs with high affinity for DNA with DNase and protease activities may be antibodies against DNA-histone complex antigenic determinants, including protein and DNA sequences. Polyreactive IgGs-abzymes against MBP, five histones, and DNA with extended cytotoxicity can play a very negative role in the pathogenesis of multiple sclerosis and probably other different diseases

Immunoglobulins with Non-Canonical Functions in Inflammatory and Autoimmune Disease States

Immunoglobulins are known to combine various effector mechanisms of the adaptive and the innate immune system. Classical immunoglobulin functions are associated with antigen recognition and the initiation of innate immune responses. However, in addition to classical functions, antibodies exhibit a variety of non-canonical functions related to the destruction of various pathogens due to catalytic activity and cofactor effects, the action of antibodies as agonists/antagonists of various receptors, the control of bacterial diversity of the intestine, etc. Canonical and non-canonical functions reflect the extreme human antibody repertoire and the variety of antibody types generated in the organism: antigen-specific, natural, polyreactive, broadly neutralizing, homophilic, bispecific and catalytic. The therapeutic effects of intravenous immunoglobulins (IVIg) are associated with both the canonical and non-canonical functions of antibodies. In this review, catalytic antibodies will be considered in more detail, since their formation is associated with inflammatory and autoimmune diseases. We will systematically summarize the diversity of catalytic antibodies in normal and pathological conditions. Translational perspectives of knowledge about natural antibodies for IVIg therapy will be also discussed

Circulating Cell-Free DNA Levels in Psychiatric Diseases: A Systematic Review and Meta-Analysis

The cell-free DNA (cfDNA) levels are known to increase in biological fluids in various pathological conditions. However, the data on circulating cfDNA in severe psychiatric disorders, including schizophrenia, bipolar disorder (BD), and depressive disorders (DDs), is contradictory. This meta-analysis aimed to analyze the concentrations of different cfDNA types in schizophrenia, BD, and DDs compared with healthy donors. The mitochondrial (cf-mtDNA), genomic (cf-gDNA), and total cfDNA concentrations were analyzed separately. The effect size was estimated using the standardized mean difference (SMD). Eight reports for schizophrenia, four for BD, and five for DDs were included in the meta-analysis. However, there were only enough data to analyze the total cfDNA and cf-gDNA in schizophrenia and cf-mtDNA in BD and DDs. It has been shown that the levels of total cfDNA and cf-gDNA in patients with schizophrenia are significantly higher than in healthy donors (SMD values of 0.61 and 0.6, respectively; p < 0.00001). Conversely, the levels of cf-mtDNA in BD and DDs do not differ compared with healthy individuals. Nevertheless, further research is needed in the case of BD and DDs due to the small sample sizes in the BD studies and the significant data heterogeneity in the DD studies. Additionally, further studies are needed on cf-mtDNA in schizophrenia or cf-gDNA and total cfDNA in BD and DDs due to insufficient data. In conclusion, this meta-analysis provides the first evidence of increases in total cfDNA and cf-gDNA in schizophrenia but shows no changes in cf-mtDNA in BD and DDs. Increased circulating cfDNA in schizophrenia may be associated with chronic systemic inflammation, as cfDNA has been found to trigger inflammatory responses