Comparison of DNA-Hydrolyzing Antibodies from the Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis

Abstract

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.

Changes in cell differentiation and proliferation lead to production of abzymes in EAE mice treated with DNA–Histone complexes

“…As demonstrated before, the method of isolation of IgGs developed by us excludes contamination with classical enzymes . Based on several very strict criteria developed previously, we have reliably proven that DNase‐, MOG‐, MBP‐hydrolysing activities are intrinsic properties of IgG abzymes from the plasma of spontaneously diseased MOG and DNA‐met‐BSA treated C57BL/6 mice, and they are not because of co‐purified canonical DNases or proteases .…”

“…Such suppression of lymphocyte apoptosis can lead to an intensive increase of various abnormal cells producing autoantibodies that are harmful for the organisms in the bone marrow and different organs. In favour of this assumption is the fact that the RAs of IgGs for hydrolysis of MBP, DNA and oligosaccharides from the CSF of MS patients are on average 50‐ to 60‐fold higher than Abs from the sera of the same patients . It seems reasonable to believe that additional amiss differentiation of lymphocytes occurs not only in different organs but already at the level of the bone marrow where the formation of cells producing auto‐Abs and abzymes results in an increase in enzymatic activities of abzymes in comparison with blood sera.…”

“…Current data demonstrate the appearance of myelin basic protein (MBP)‐ and DNA‐hydrolysing abzymes in the blood of patients with MS, SLE and several other AIDs . IgGs from the CSF of MS patients, which hydrolyse MBP, DNA and polysaccharides, are on average 30‐ to 60‐fold higher than those taken from the sera of the same patients . In AIDs, abzymes hydrolysing MBP can attack the protein of the myelin‐proteolipid sheath of axons and can play a harmful role in MS, SLE and other disease pathogenesis .…”

Catalytic Antibodies in Norm and Systemic Lupus Erythematosus

“…It was shown that IgGs from sera and cerebrospinal fluid of MS patients are active in the hydrolysis of DNA, MBP, and oligosaccharides. In addition, the specific RAs of these abzymes from the CSF of MS patients are dependently on their different activities were approximately 30-to 60-fold higher comparing to serum Abzs from the same patients [67][68][69]. It means that during spontaneous or induced development of ADs as a result of specific differentiation of lymphocytes in cerebrospinal fluid there may be formation of cells producing different catalytic antibodies directly in cerebrospinal fluid.…”

“…In this regard, data comparing relative Abz activities from serum and cerebrospinal fluid (CSF) of the same MS patients with multiple sclerosis should be noted [67][68][69]. It was shown that IgGs from sera and cerebrospinal fluid of MS patients are active in the hydrolysis of DNA, MBP, and oligosaccharides.…”