IgGs containing light chains of the λ and κ type and of all subclasses (IgG1‐IgG4) from sera of patients with multiple sclerosis hydrolyze DNA

Abstract

We present the first evidence demonstrating that small fractions of IgGs of all four subclasses (IgG1-IgG4) are catalytically active in the hydrolysis of DNA and on average their relative activity (nM supercoiled DNA/1mg IgG/1 h) increases in the order: IgG1 (0.58) < IgG2 (0.94) < IgG3 (1.4) < IgG4 (4.1), while their approximate relative contribution to the total activity of abzymes increases in the order: IgG1 (6.9%) < IgG3 (9.3%) < IgG2 (18.2%) < IgG4 (65.6%). On average IgGs containing light chains of the lambda-type are severalfold more active in the hydrolysis of DNA than IgGs with light chains of the kappa-type. Using different physicochemical methods of antibody analysis we have shown that the immune system of multiple sclerosis patients generates a variety of anti-DNA abzymes of different type and with different catalytic properties, which can play an important role in multiple sclerosis pathogenesis.

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

“…The coefficient of correlation between the anti‐hMBP Abs titers (A 450 ) and RAs of Abs was 0.79 ( p < 0.05). Similar correlation coefficients (0.73–0.8) between the anti‐DNA Abs titers (A 450 ) and DNase relative activities of Abs were observed earlier in the case of patients with tick‐borne encephalitis and several AI diseases (Nevinsky and Buneva, ; Parkhomenko et al ., ).…”

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

“…Patients may have an extremely large pool of polyclonal Abs hydrolysing many different substrate abzymes containing light chains of kappa‐ and lambda‐types, having different net charges, demonstrating different pH optima, may be metal‐independent or independent on different metal ions, and characterized by different substrate specificities . Small fractions of IgGs of four subclasses (IgG1–IgG4) from SLE and MS patients are catalytically active in the hydrolysis of DNA and MBP . This may indicate that various ways of violations of the bone marrow immune system can lead to the production of different autoantibodies and abzymes with diverse enzymatic activities in the case of different AIDs.…”

IgGs containing λ‐ and κ‐type light chains and of all subclasses (IgG1–IgG4) from the sera of patients with autoimmune diseases and viral and bacterial infections hydrolyze DNA

“…Electrophoretically and immunologically homogeneous pIgGs from 10 patients with SLE, MS, TBE, SI, and SSI and healthy donors were obtained by sequential affinity chromatography of the serum proteins on protein G‐Sepharose and FPLC gel filtration on a Superdex 200 HR 10/30 column similarly to Parkhomenko et al . () and Bezuglova et al . ().…”

“…The analysis of the DNase activity of different types of MS IgGs was performed previously by Parkhomenko et al . (). In this article, for the comparison and confirmation of previously published results, a new set of MS and SLE IgGs was used.…”