HIV-Infected Patients: Cross Site-Specific Hydrolysis of H2a and H2b Histones and Myelin Basic Protein with Antibodies against These Three Proteins (original) (raw)
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Peptides, 2012
IgGs from patients with multiple sclerosis and systemic lupus erythematosus (SLE) purified on MBP-Sepharose in contrast to canonical proteases hydrolyze effectively only myelin basic protein (MBP), but not many other tested proteins. Here we have shown for the first time that anti-MBP SLE IgGs hydrolyze nonspecific tri-and tetrapeptides with an extreme low efficiency and cannot effectively hydrolyze longer 20-mer nonspecific oligopeptides corresponding to antigenic determinants (AGDs) of HIV-1 integrase. At the same time, anti-MBP SLE IgGs efficiently hydrolyze oligopeptides corresponding to AGDs of MBP. All sites of IgG-mediated proteolysis of 21-and 25-mer encephalytogenic oligopeptides corresponding to two known AGDs of MBP were found by a combination of reverse-phase chromatography, TLC, and MALDI spectrometry. Several clustered major, moderate, and minor sites of cleavage were revealed in the case of 21-and 25-mer oligopeptides. The active sites of anti-MBP abzymes are localised on their light chains, while heavy chains are responsible for the affinity of protein substrates. Interactions of intact globular proteins with both light and heavy chains of abzymes provide high affinity to MBP and specificity of this protein hydrolysis. The affinity of anti-MBP abzymes for intact MBP is approximately 1000-fold higher than for the oligopeptides. The data suggest that all oligopeptides interact mainly with the light chains of different monoclonal abzymes of total pool of IgGs, which possesses a lower affinity for substrates, and therefore, depending on the oligopeptide sequences, their hydrolysis may be less specific than globular protein and can occur in several sites.
ScienceRise: Medical Science
It was shown that in HIV-infected patients, pathomorphological changes in the white matter in the form of demyelinization are already observed in the early stages of the disease. The most studied marker of this process is myelin basic protein that can be detected in cerebrospinal fluid or serum immediately after acute myelin breakdown. The aim. To assess the diagnostic value of myelin basic protein content in serum and cerebrospinal fluid of HIV-infected individuals with 4th clinical stage and central nervous system opportunistic infections. Materials and methods. Using ELISA with diagnostic kit “MBP ELISA” (Ansh Labs, USA), we studied the myelin basic protein content in serum and cerebrospinal fluid of 53 HIV-infected patients with 4th clinical stage and central nervous system opportunistic infections depending on its etiology, the outcome of the diseases and according to Glasgow coma scale score. As well correlation analysis with some laboratory and clinical indicators was perform...
Antibodies against peripheral myelin glycolipids in people with HIV infection
Immunology and Cell Biology, 1998
Plasma samples from 35 individuals with HIV infection but without clinical peripheral neuropathy were screened by ELISA for IgM and IgG antibodies against peripheral myelin. Eighteen of the 35 samples (51%) showed IgM reactivity and 11 (31%) showed IgG reactivity. By comparison, none of 48 samples from healthy blood donors showed IgM or IgG reactivity. Epitopes reacting with these antibodies were identi®ed by TLC immunostaining as sulphatide (GalS) and the gangliosides GM 1 , GD 1a and GD 1b. Plasma samples from four people with HIV infection and neuropathy (HIV + PN), six HIV-seronegative individuals with IgM paraproteinaemic demyelinating neuropathy (IgMPDN) and 12 HIV-seronegative individuals with a variety of other neurological disorders (HIV ± OND) were also investigated. Two of the four HIV + PN samples showed IgM reactivity with GalS; and two showed IgG reactivity against GalS. Of the six IgMPDN samples, three showed IgM reactivity with GalS. These data indicate that antibodies against peripheral myelin glycolipids, in particular GalS, occur more frequently in HIV infection than in HIV-seronegative individuals with and without neurological disease, and may contribute to subclinical neuropathy in HIV infection.
Biochemistry (Moscow), 2015
Artificial catalytically active antibodies, or abzymes, against transition states of different chemical reactions have been described in the literature in recent years [1]. Natural abzymes hydrolyzing DNA, RNA, polysaccha-rides, oligopeptides (OPs), and proteins from blood of patients with different autoimmune diseases (systemic lupus erythematosus (SLE), Hashimoto's thyroiditis, polyarthritis, multiple sclerosis (MS), asthma, rheumatoid arthritis, etc.) and some viral infections are accompanied by disorders in immune status (hepatitis, HIVinfection, tick-borne encephalitis) [2-6]. In healthy donors and patients with many other diseases accompanied by poorly pronounced autoimmune reactions, abzymes are not produced, the generated antibodies (ABs) have low catalytic activities, and such ABs cannot be reliably detected by current methods [2-6]. In addition to classic functions of ABs, abzymes can play both positive and negative roles inducing specific processes and
Clinical and Experimental Immunology, 1996
SUMMARY Levels of autoantibodies specific for the histone, H2B, were measured in individuals with HIV infection. In comparison with normal (uninfected) controls, infected patients, particularly those with symptomatic disease, had significantly elevated titres of anti-H2B antibodies. Longitudinal studies confirmed that levels of these antibodies were highest in patients with lymphadenopathy and declined with the development of AIDS. In preliminary experiments designed to determine the biological significance of the anti-histone antibodies, H2B was shown to be immunologically cross-reactive with an 18-kD antigen on the surface of HIV-infected or mitogen-activated CD4+ cells. Protein sequencing of the 18-kD antigen has since shown complete homology with histone H2B. Because the titres of H2B autoantibodies were found to parallel the numbers of circulating CD4 cells, it is possible that these antibodies are involved in the destruction of the helper/inducer T lymphocyte population.
A N D Properties of Monoclonal Antibodies to Myelin Basic Protein and Its Peptides
2002
A~tract--Techniques are described which have enabled the production and characterisation of monoclonal antibodies to myelin basic protein. These are shown by enzyme immunoassay to react with six different epitopes. Two of these are to peptide 82-91, a region claimed to be present in the spinal fluid of patients with demyelinating disease. One of these, an IgG~, is shown to react only with peptides in which the 91-92 phe-phe bond has broken. The other, an IgM, also reacts with whole myelin basic protein. The IgG2~ antibody is shown to have an affinity suitable for use in immunoassay of peptide 82-91. The enzyme immunoassay procedures described help to minimise the work load involved in the preparation and characterisation of monoclonal antibodies to this protein.
2010
Recently we have shown the presence of catalytically active IgGs, capable to cleave histone H1 and bovine myelin basic protein (MBP), in blood serum of SLE patients. Here we present data that demonstrate the correlation between a) proteolytic activity towards histone H1 and MBP of IgG-antibodies from blood serum of SLE patients and b) disease severity level in these patients. IgGs were isolated from blood serum by chromatography on protein G-sepharose. Commercial preparations of bovine myelin basic proteins (MBP) and calf thymus histone H1 were used as substrates. Analysis of the proteolytic activity showed that 16 of 38 lgG-preparations (42,1%) obtained from blood serum of SLE patients were capable of cleaving both histone H1 and MBP with different efficiency. It was revealed that the presence in blood serum of lgGs possessing proteolytic activity towards both histone H1 and bMBP closely correlates with manifestation of the disease severity in SLE patients.