Abstract
It was recently shown that IgGs from sera of multiple sclerosis (MS) patients are active in the hydrolysis of DNA and myelin basic protein (MBP). We first analyzed the relative concentration of antibodies against five histones (H1, H2a, H2b, H3, and H4) in the cerebrospinal fluid (CSF) and serum of patients with MS. The relative concentrations of blood and CSF IgGs against histones and their activity in the hydrolysis of five histones varied greatly from patient to patient. However, all 28 IgG preparations were hydrolyzed from one to five histones. Relative activities and correlation coefficients among the activities of IgGs from serum and CSF in the hydrolysis of five histones (H1, H2a, H2b, H3, and H4), DNA, and MBP were calculated. It was shown that auto-IgGs from CSF and sera of MS patients are extremely heterogeneous in their affinity to histones, MBP, and DNA. The heterogeneity of IgG-abzymes hydrolyzing DNA, MBP, and histones from CSF and sera was also demonstrated using their isoelectrofocusing. The isofocusing profiles DNase, MBP-, and histone-hydrolyzing activities of IgGs may be very different for various individuals, but the total IgG subfractions with all their activities are distributed from pH 3 to 10.
Highlights
Multiple sclerosis (MS) presenting a serious medical and social problem is a chronic demyelinating pathology of the central nervous system
For the first time, we analyzed the diversity of auto-antibodies from the cerebrospinal fluid and blood of patients with MS by their affinity for DNA, myelin basic protein (MBP), and histones, as well as the distribution of IgGs hydrolyzing these substrates at isoelectric points after antibody isoelectric focusing
The relative activities (RAs) of different IgGs were determined from a decrease in the percentage of non-hydrolyzed proteins converted to their different shorted forms, taking into account percentage of the hydrolysis of control MBP or histones without Abs
Summary
Multiple sclerosis (MS) presenting a serious medical and social problem is a chronic demyelinating pathology of the central nervous system. By using isoelectrofocusing with following antigen-specific immunoblotting, specific OCBs in CSF of some MS patients were revealed definitely against the only components of Epstein–Barr virus [8] and Chlamydia [9] It is still unknown which human auto-antigens oligoclonal antibodies may be produced in MS patients. It was shown that myelin basic protein (MBP)-, DNA-, and oligosaccharide-hydrolyzing activities are intrinsic property of IgGs, IgMs, and IgAs from sera of MS and SLE patients [17,18,19,20,21,22]. For the first time, we analyzed the diversity of auto-antibodies from the cerebrospinal fluid and blood of patients with MS by their affinity for DNA, MBP, and histones, as well as the distribution of IgGs hydrolyzing these substrates at isoelectric points (pI) after antibody isoelectric focusing. It has been shown that in CSFs and sera, IgGs are characterized by exceptional diversity in affinity for the antigens and the relative catalytic activities
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