Multiple Sclerosis: Enzymatic Cross Site-Specific Hydrolysis of H1 Histone by IgGs against H1, H2A, H2B, H3, H4 Histones, and Myelin Basic Protein.

Histones play a key role in chromatin remodeling and gene transcription. Further, free histones in the blood act as damage-associated molecules. Administration of histones to animals results in systemic inflammatory and toxic effects. Myelin basic protein is the principal constituent element of the myelin-proteolipid sheath of axons. Abzymes (antibodies with catalytic activities) are the original features of some autoimmune diseases. In this study, electrophoretically homogeneous IgGs against H1, H2A, H2B, H3, and H4 histones and myelin basic protein (MBP) were isolated from the blood sera of multiple sclerosis (MS) patients by several affinity chromatographies. Using MALDI mass spectrometry, the sites of H1 histone cleavage by IgGs against H1, H2A, H2B, H3, H4, and MBP were determined. It was shown that IgGs against H1 split H1 at 12 sites, while the number of cleavage sites by abzymes against other histones was lower: H2A (9), H2B (7), H3 (3), and H4 (3). The minimum rate of H1 hydrolysis was observed for antibodies against H3 and H4. A high rate of hydrolysis and the maximum number of H1 hydrolysis sites (17) were found for antibodies against MBP. Only a few sites of H1 hydrolysis by anti-H1 antibodies coincided with those for IgGs against H2A, H2B, H3, H4, and MBP. Thus, the polyreactivity of complexation and the enzymatic cross-activity of antibodies against H1, four other histones, and MBP have first been shown. Since histones act as damage molecules, abzymes against histones and MBP can play a negative role in the pathogenesis of MS and probably other different diseases as well.

IgGs-Abzymes from the Sera of Patients with Multiple Sclerosis Recognize and Hydrolyze miRNAs.

Autoantibodies-abzymes hydrolyzing DNA, myelin basic protein, and oligosaccharides have been revealed in the sera of patients with multiple sclerosis (MS). In MS, specific microRNAs are found in blood and cerebrospinal fluid, which are characterized by increased expression. Autoantibodies, specifically hydrolyzing four different miRNAs, were first detected in the blood of schizophrenia patients. Here, we present the first evidence that 23 IgG antibodies of MS patients effectively recognize and hydrolyze four neuroregulatory miRNAs (miR-137, miR-9-5p, miR-219-2-3p, and miR-219-5p) and four immunoregulatory miRNAs (miR-21-3p, miR-146a-3p, miR-155-5p, and miR-326). Several known criteria were checked to show that the recognition and hydrolysis of miRNAs is an intrinsic property of MS IgGs. The hydrolysis of all miRNAs is mostly site-specific. The major and moderate sites of the hydrolysis of each miRNA for most of the IgG preparations coincided; however, some of them showed other specific sites of splitting. Several individual IgGs hydrolyzed some miRNAs almost nonspecifically at nearly all internucleoside bonds or demonstrated a combination of site-specific and nonspecific splitting. Maximum average relative activity (RA) was observed in the hydrolysis of miR-155-5p for IgGs of patients of two types of MS-clinically isolated syndrome and relapsing-remitting MS-but was also high for patients with primary progressive and secondary progressive MS. Differences between RAs of IgGs of four groups of MS patients and healthy donors were statistically significant (p < 0.015). There was a tendency of decreasing efficiency of hydrolysis of all eight miRNAs during remission compared with the exacerbation of the disease.

Blood-Derived RNA- and microRNA-Hydrolyzing IgG Antibodies in Schizophrenia Patients.

Abzymes with various catalytic activities are the earliest statistically significant markers of existing and developing autoimmune diseases (AIDs). Currently, schizophrenia (SCZD) is not considered to be a typical AID. It was demonstrated recently that antibodies from SCZD patients efficiently hydrolyze DNA and myelin basic protein. Here, we showed for the first time that autoantibodies from 35 SCZD patients efficiently hydrolyze RNA (cCMP > poly(C) > poly(A) > yeast RNA) and analyzed site-specific hydrolysis of microRNAs involved in the regulation of several genes in SCZD (miR-137, miR-9-5p, miR-219-2-3p, and miR-219a-5p). All four microRNAs were cleaved by IgG preparations (n = 21) from SCZD patients in a site-specific manner. The RNase activity of the abzymes correlated with SCZD clinical parameters. The data obtained showed that SCZD patients might display signs of typical autoimmune processes associated with impaired functioning of microRNAs resulting from their hydrolysis by the abzymes.

[Exceptional Diversity of Catalytic Antibodies with Varying Activity in the Blood of Autoimmune and Viral Disease Patients].

Antibodies (ABs) that target autoantigens were more abundant in the blood of humans and animals suffering from certain autoimmune and viral diseases than in the blood of healthy donors. The emergence of ABs with diverse types of catalytic activity is among the earliest manifestations of certain autoimmune diseases. The putative mechanisms that underlie the accumulation of autoantibodies and abzymes in different autoimmune diseases are addressed in the present review. The extraordinary diversity of abzymes with various types of catalytic activity is discussed.

Augmenting the efficacy of anti-cocaine catalytic antibodies through chimeric hapten design and combinatorial vaccination.

Given the need for further improvements in anti-cocaine vaccination strategies, a chimeric hapten (GNET) was developed that combines chemically-stable structural features from steady-state haptens with the hydrolytic functionality present in transition-state mimetic haptens. Additionally, as a further investigation into the generation of an improved bifunctional antibody pool, sequential vaccination with steady-state and transition-state mimetic haptens was undertaken. While GNET induced the formation of catalytically-active antibodies, it did not improve overall behavioral efficacy. In contrast, the resulting pool of antibodies from GNE/GNT co-administration demonstrated intermediate efficacy as compared to antibodies developed from either hapten alone. Overall, improved antibody catalytic efficiency appears necessary to achieve the synergistic benefits of combining cocaine hydrolysis with peripheral sequestration.

Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis.

We have recently shown that IgGs from serum and cerebrospinal fluid (CSF) of MS patients are active in hydrolysis of DNA and myelin basic protein. According to literature data, anti-DNA and anti-MBP abzymes may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. At the same time, the involvement of antibodies with amylase activity in the pathogenesis of any autoimmune disease has not yet been identified. Electrophoretically and immunologically homogeneous IgGs were obtained by a sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We are able to present the first unpredictable evidence showing that IgGs from CSF possess amylase activity and efficiently hydrolyze maltoheptaose; their average specific Ab activity is ~30-fold higher than that of antibodies from sera of the same MS patients. Specific average RA (SAA) for IgGs from healthy volunteers was approximately ~1000 lower than that for MS patients. In addition, it was shown that a relative SAA of total proteins of CSF (including Abs) ~15-fold lower than that for purified IgGs, while the relative SAA of the total sera protein is higher than that of sera IgGs by a factor of 1033. This result speaks in favor of the fact that amylolytic activity of CSF proteins is mainly caused by the activity of amylase abzymes. One cannot exclude, that amylase abzymes of CSF can play a, as yet unknown, role in the pathogenesis of MS. Some possible reasons of these findings are discussed.

DNA-hydrolysing activity of IgG antibodies from the sera of patients with schizophrenia.

It is believed that damage to the membranes of brain cells of schizophrenia (SCZ) patients induces the formation of autoantigens and autoantibodies. Nevertheless, the importance of immunological changes leading to the loss of tolerance to self-antigens in the genesis of SCZ has not been established. The MALDI mass spectra of the IgG light chains of 20 healthy donors were relatively homogeneous and characterized by one peak with only one maximum. In contrast to the healthy donors, the MALDI mass spectra of IgG light chains corresponding to 20 SCZ patients demonstrated, similarly to 20 autoimmune systemic lupus erythematosus (SLE) patients, two maxima of a comparable intensity. In addition, the MALDI spectra of the IgG light chains of five SLE and four SCZ patients contained a small additional brightly pronounced peak with remarkably lower molecular mass compared with the main one. DNase autoantibodies (abzymes) can be found in the blood of patients with several autoimmune diseases, while the blood of healthy donors or patients with diseases without a significant disturbance of the immune status does not contain DNase abzymes. Here, we present the first analysis of anti-DNA antibodies and DNase abzymes in the sera of SCZ patients. Several strict criteria have been applied to show that the DNase activity is an intrinsic property of IgGs from the sera of SCZ patients. The sera of approximately 30% of SCZ patients displayed a higher content of antibodies (compared with 37% of SLE) interacting with single- and double-stranded DNA compared with healthy donors. Antibodies with DNase activity were revealed in 80% of the patients. These data indicate that some SCZ patients may show signs of typical autoimmune processes to a certain extent.

IgG abzymes with peroxidase and oxidoreductase activities from the sera of healthy humans.

We present the evidence showing that small fractions of electrophoretically homogeneous immunoglobulin G (IgGs) from the sera of healthy humans and their Fab and F(ab)2 fragments oxidize 3,3'-diaminobenzidine through a peroxidase activity in the presence of H2 O2 and through an oxidoreductase activity in the absence of H2 O2 . During purification on protein G-Sepharose and gel filtration, the polyclonal IgGs partially lose the Me(2+) ions. After extensive dialysis of purified Abs against agents chelating metal ions, the relative peroxidase activity decreased dependently of IgG analyzed from 100 to ~10-85%, while oxidoreductase activity from 100 to 14-83%. Addition of external metal ions to dialyzed and non-dialyzed IgGs leads to a significant increase in their activity. Chromatography of the IgGs on Chelex non-charged with Cu(2+) ions results in the adsorption of a small IgG fraction bound with metal ions (~5%), while Chelex charged with Cu(2+) ions bind additionally ~38% of the total IgGs. Separation of Abs on both sorbents results in IgG separation to many different subfractions demonstrating various affinities to the chelating resin and different levels of the specific oxidoreductase and peroxidase activities. In the presence of external Cu(2+) ions, the specific peroxidase activity of several IgG subfractions achieves 20-27 % as compared with horseradish peroxidase (HRP, taken for 100%). The oxidoreductase activity of these fractions is ~4-6-fold higher than that for HRP. 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. Peroxidase and oxidoreductase activities of human IgGs could also play an important role in the protection of organisms from oxidative stress and toxic compounds.

Comparison of DNA-hydrolyzing antibodies from the cerebrospinal fluid and serum of patients with multiple sclerosis.

It was found that high-affinity anti-DNA antibodies were one of the major components of the intrathecal IgG response in multiple sclerosis (MS) patients [Williamson et al., PNAS, 2001]. Recently we have shown that IgGs from the sera of MS patients are active in the hydrolysis of DNA. Here we have shown, for the first time, that average concentration of total proteins (132-fold), total IgGs (194-fold) and anti-DNA antibodies (200-fold) in the sera is significantly higher than that in the cerebrospinal fluid (CSF) of fifteen MS patients. The relative activities of total protein from sera and CSFs varied remarkably from patient to patient. It was surprising that the specific DNase activity of the total protein of CSF reparations were 198-fold higher than the serum ones. Electrophoretically and immunologically homogeneous IgGs were obtained by sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We present first evidence showing that IgGs from CSF not only bind but efficiently hydrolyze DNA and that average specific DNase activity of homogeneous antibodies from CSF is unpredictably ∼49-fold higher than that from the sera of the same MS patients. Some possible reasons of these findings are discussed. We suggest that DNase IgGs of CSF may promote important neuropathologic mechanisms in this chronic inflammatory disorder and MS pathogenesis development.

Proteolytic activity of IgGs from blood serum of Wistar rats at experimental rheumatoid arthritis.

The aim of this work was to study the proteolytic activity of IgGs purified from blood serum of Wistar rats at experimental rheumatoid arthritis (ERA) induced by an injection of bovine collagen of type II. Twenty rats were immunized with a preparation of bovine collagen II (Sigma-Aldrich, USA) in the presence of complete Freund's adjuvant. ERA development was determined by inflammation in limbs of treated animals. IgG preparations were isolated from blood serum of immunized and non-immunized animals by precipitation of antibodies with 33% ammonium sulfate followed by chromatography on the Protein G-Sepharose column. Human histone H1, bovine collagen II, calf thymus histones, myelin basic protein (MBP), bovine serum albumin (BSA), and bovine casein were used as substrates of the proteolytic activity of IgGs. It was found that IgG preparations from blood serum of rats with ERA were capable of cleaving histone H1 and MBP, however, they were catalytically inactive towards collagen II, casein, BSA, and core histones. IgGs from blood serum of non-immunized rats were proteolytically inactive towards all used protein substrates. Thus, we demonstrated that immunization of rats with bovine collagen II induced IgG-antibodies possessing the proteolytic activity towards histone H1 and MBP. This activity might be associated with the development of inflammatory processes in the immunized rats.

IVIg treatment reduces catalytic antibody titers of renal transplanted patients.

Catalytic antibodies are immunoglobulins endowed with enzymatic activity. Catalytic IgG has been reported in several human autoimmune and inflammatory diseases. In particular, low levels of catalytic IgG have been proposed as a prognostic marker for chronic allograft rejection in patients undergoing kidney transplant. Kidney allograft is a treatment of choice for patients with end-stage renal failure. Intravenous immunoglobulins, a therapeutic pool of human IgG, is used in patients with donor-specific antibodies, alone or in conjunction with other immunosuppressive treatments, to desensitize the patients and prevent the development of acute graft rejection. Here, we followed for a period of 24 months the levels of catalytic IgG towards the synthetic peptide Pro-Phe-Arg-methylcoumarinimide in a large cohort of patients undergoing kidney transplantation. Twenty-four percent of the patients received IVIg at the time of transplantation. Our results demonstrate a marked reduction in levels of catalytic antibodies in all patients three months following kidney transplant. The decrease was significantly pronounced in patients receiving adjunct IVIg therapy. The results suggests that prevention of acute graft rejection using intravenous immunoglobulins induces a transient reduction in the levels of catalytic IgG, thus potentially jeopardizing the use of levels of catalytic antibodies as a prognosis marker for chronic allograft nephropathy.

Effect of CoCl2 on the content of different metals and a relative activity of DNA-hydrolyzing abzymes in the blood plasma of mice.

Cobalt is a transition metal and an essential trace element that is required for vitamin B12 biosynthesis, enzyme activation, and so on but is toxic in high concentrations. It was shown that the content of different elements in the plasma of 2-month-old BALB/c mice (control group) decreased in the following order: Ca > Mg > Si > Fe > Zn > Cu ≥ Al ≥ B. The treatment of mice with CoCl2 did not appreciably change the relative content of Ca, Cu, and Zn, but a significant increase in the content of B (2.3-fold), Mg (1.5-fold), Al and Fe (2.1-fold), and Si (3.4-fold) was found. The treatment of mice led to a 2.2-fold decrease in the concentration of the total blood protein and a 1.7 ± 0.2-fold decrease of total immunoglobulin Gs (IgGs). Deoxyribonuclease IgGs corresponding to mice treated (t-IgGs) and non-treated (nt-IgGs) with CoCl2 contained intrinsically bound metal ions; these IgGs hydrolyzed DNA with very low activity but were not active in the presence of ethylenediaminetetraacetic acid or after Ab dialysis against ethylenediaminetetraacetic acid. The average RAs of deoxyribonuclease nt-IgGs increased after addition of external metal ions in the following order: Zn²âº< Ca²âº < Cu²âº < Fe²âº < Mn²âº < Mg²âº < Co²âº < Ni²âº. Interestingly, t-IgGs demonstrated lower activities than those for nt-IgGs either in the absence of external metal ions (2.7-fold) or in the presence of Cu²âº (9.5-fold) > Co²âº (5.6-fold) > Zn²âº (5.1-fold) > Mg²âº (4.1-fold) > Ca²âº (3.0-fold) > Fe²âº (1.3-fold). However, the RAs of t-IgGs were remarkably more active than nt-IgGs in the presence of best activators of t-IgGs Ni²âº (1.4-fold) and especially Mn²âº (2.2-fold). The data may be useful for an understanding of Co toxicity, its effect on the concentration of other metal ions, and a change of metal-dependent specificity of Abzs.

Anti-integrase abzymes from the sera of HIV-infected patients specifically hydrolyze integrase but nonspecifically cleave short oligopeptides.

In contrast to canonical proteases, total immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies (Abs) from HIV-infected patients hydrolyze effectively only HIV integrase (IN), reverse transcriptase (RT), human casein, and serum albumin. Anti-IN IgG and IgM isolated by chromatography on IN-Sepharose hydrolyze specifically only IN but not many other tested proteins. Total Abs from HIV-infected patients hydrolyze not only globular proteins but also different specific and nonspecific tri-, tetra-, and 20- to 25-mer oligopeptides (OPs) with a higher rate than anti-IN Abs isolated using IN-Sepharose. A similar situation was observed for IgG from patients with multiple sclerosis and HIV-infected patients, which after purification on myelin basic protein (MBP)-Sepharose and RT-Sepharose specifically hydrolyze only MBP and RT, respectively. The active sites of all anti-protein abzymes are localized on their light chains, whereas the heavy chain is responsible for the affinity of protein substrates. Interactions of intact globular proteins with both light and heavy chains of abzymes provide the specificity of protein hydrolysis. The affinity of anti-IN and anti-MBP abzymes for intact IN and MBP is approximately 10(2)- to 10(5)-fold higher than for short and long specific and nonspecific OPs. The data suggest that all OPs interact mainly with the light chain of different Abs, which possesses a lower affinity for substrates, and therefore, depending on the OP sequences, their hydrolysis may be less specific or completely nonspecific. The data indicate that the relative activity of Abs not fractionated on specific protein sorbents in the hydrolysis of specific and nonspecific OPs can correspond to an average proteolytic activity of light chains of polyclonal Abs directed against many different proteins.

Constitutive production of catalytic antibodies to a Staphylococcus aureus virulence factor and effect of infection.

Antibodies that recognize microbial B lymphocyte superantigenic epitopes are produced constitutively with no requirement for adaptive immune maturation. We report cleavage of the Staphylococcus aureus virulence factor extracellular fibrinogen-binding protein (Efb) by catalytic antibodies produced with no exposure to the bacterium and reduction of the catalytic antibody activity following infection. IgG catalytic antibodies that specifically hydrolyzed Efb via a nucleophilic catalytic mechanism were found in the blood of healthy humans and aseptic mice free of S. aureus infection. IgG hydrolyzed peptide bonds on the C-terminal side of basic amino acids, including a bond located within the C3b-binding domain of Efb. Efb digested with the IgG lost its ability to bind C3b and inhibit complement-dependent antibody-mediated red blood cell lysis. In addition to catalysis, the IgG expressed saturable Efb binding activity. IgG from S. aureus-infected mice displayed reduced Efb cleaving activity and increased Efb binding activity compared with uninfected controls, suggesting differing effects of the infection on the antibody subsets responsible for the two activities. IgG from children hospitalized for S. aureus infection also displayed reduced Efb cleavage compared with healthy children. These data suggest a potential defense function for constitutively produced catalytic antibodies to a putative superantigenic site of Efb, but an adaptive catalytic response appears to be proscribed.

Diversity of integrase-hydrolyzing IgGs and IgMs from sera of HIV-infected patients.

It was previously shown that small fractions of IgGs and IgMs from the sera of AIDS patients specifically hydrolyze only HIV integrase (IN) but not many other tested proteins. Here we present evidence showing that these IgGs and IgMs are extreme catalytically heterogeneous. Affinity chromatography on IN-Sepharose using elution of IgGs (or IgMs) with different concentration of NaCl and acidic buffer separated catalytic antibodies (ABs) into many AB subfractions demonstrating different values of K(m) for IN and k(cat). Nonfractionated IgGs and IgMs possess serine-, thiol-, acidic-like, and metal-dependent proteolytic activity. Metal-dependent activity of abzymes increases in the presence of ions of different metals. In contrast to canonical proteases having one pH optimum, initial nonfractionated IgGs and IgMs demonstrate several optima at pH from 3 to 10. The data obtained show that IN-hydrolyzing polyclonal IgG and IgM of HIV-infected patients are cocktails of anti-IN ABs with different structure of the active centers possessing various affinity to IN, pH optima, and relative rates of the specific substrate hydrolysis.

Affinity and catalytic heterogeneity and metal-dependence of polyclonal myelin basic protein-hydrolyzing IgGs from sera of patients with systemic lupus erythematosus.

It was shown using enzyme-linked immunosorbent assay (ELISA) that titers of antibodies against human myelin basic protein (hMBP) in systemic lupus erythematosus (SLE) patients 4.2-fold higher than in healthy individuals, but 2.1-fold lower than in patients with multiple sclerosis (MS). Approximately 86% electrophoretically and immunologically homogeneous SLE immunoglobulin Gs (IgGs) purified using several affinity resins including Sepharose with immobilized hMBP specifically hydrolyze only hMBP but not many other tested proteins. Several rigid criteria were applied to show that the hMBP-hydrolyzing activity is an intrinsic property of SLE IgGs but not from healthy donors. In contrast to MS IgGs, abzymes from SLE patients are more sensitive to ethylenediaminetetraacetic acid and less sensitive to specific inhibitors of serine-like proteases. We present the first evidence demonstrating a significant diversity of different fractions of SLE IgGs in their affinity for hMBP-Sepharose, the ability of IgGs to hydrolyze hMBP at different optimal pHs (5-10) and be activated by different metal ions: Ca(2+) > Mg(2+) ≥ Co(2+) ≥ Fe(2+) ≥ Ni(2+) ≥ Zn(2+) ≥ Cu(2+) ≥ Mn(2+) . Combinations of Ca(2+) + Mg(2+) and Ca(2+) + Co(2) lead to a significant increase in the antibody proteolytic activity as compared with Ca(2+) , Co(2+) , or Mg(2+) ions taken separately. Our findings suggest that the immune systems of individual SLE similar to MS patients can generate a variety of anti-hMBP abzymes with different catalytic properties, which can attack hMBP of myelin-proteolipid shell of axons and play an important role in pathogenesis not only MS but also SLE patients.

[Proteolytic activity of blood serum IgG in patients with systemic lupus erythematosis].

Proteolytic activity of blood serum IgGs of 10 patients with systemic lupus erythematosis (SLE) was studied in comparison with such activity in 10 clinically healthy donors. Antibodies were precipitated from blood serum by saturation with 50% (NH4)2SO4 and IgG was isolated by the affinity chromatography on protein G-sepharose column. Histone H1 and core histones from the calf thymus, bovine myelin basic protein (MBP), lysozyme of chicken egg and bovine serum albumin (BSA) were used as substrates for proteolytic action. It was found that 4 of 10 preparations of IgGs possess an ability to hydrolyze both histone H1 and MBP. These antibodies practically did not cleave lysozyme of the chicken egg and BSA. Gel-filtration of antibodies under acidic condition and following examination of proteolytic activity of chromatographic fractions showed that histone H1 and MBP-hydrolyzing activity is attributable to IgG-antibodies. Thus, the presence of catalytically active antibodies (protabzymes) in the blood serum of patients with SLE has been demonstrated. Their origination and biological role are discussed.

Peculiarities of abzymes from sera and milk of healthy donors and patients with autoimmune and viral diseases.

The detection of catalytic activity of antibodies is the earliest indicator of development of autoimmune diseases (AID). In early stages of AID, the repertoire of abzymes with various properties is relatively small, but it is greatly increased during their development. Catalytic diversity of the abzymes includes DNase, RNase, ATPase, and oxidoreductase activities; there are antibodies phosphorylating proteins, lipids, and polysaccharides. This review summarizes new data on abzyme heterogeneity and possible reasons for this phenomenon. A possible role of abzymes and their exceptional multiplicity in the pathogenesis of different AID is discussed.

[Significance of determination of lipid-oxidizing catalytic antibodies in patients with ischemic heart diseases].

From the previously examined patients with ischemic heart disease (IHD), the authors formed two groups in whom an original method was used to detect the abnormal lipid-oxidizing anti-Chlamydia antibodies abzymes that increased the serum concentration of malondialdehyde. The effects of the statin rosuvastatin and the antioxidant licopin on abzymes were comparatively studied. Despite the positive impact of therapy with rosuvastatin on lipid metabolism of IHD patients, the agent exerted no effect on the rate of lipid peroxidation and the activity of lipid-oxidizing antibodies. Licopin intake caused statistically significant lipid metabolic changes in patients with IHD. The antioxidant activity of licopin neutralized the pathogenic effect of lipid-oxidizing anti-Chlamydia abzymes.

Suppression of ongoing experimental allergic encephalomyelitis in DA rats by novel peptide drug, structural part of human myelin basic protein 46-62.

Previously, we demonstrated that autoantibodies (AAb) in multiple sclerosis (MS) reveal site-specific binding and cleavage toward myelin basic protein (MBP) epitope library. We have found several fragments of MBP immunodominant in terms of AAb binding. Here, we applied these peptides to DA rats with induced protracted relapsing experimental allergic encephalomyelitis (EAE) most closely related to MS. DA rats with EAE induced by syngenic spinal cord homogenate in complete Freund's adjuvant were treated by nasal route with human MBP 46-62, 81-102, 124-139, 147-170, and Copaxone. MBP 124-139 and 147-170 displayed only mild therapeutic effects but MBP 46-62 significantly reduced EAE, reflected by lower clinical scores and shorter EAE duration compared to controls.