Antibodies from the Sera of Multiple Sclerosis Patients Efficiently Hydrolyze Five Histones.

Baranova Baranova,Nevinsky Nevinsky,Mikheeva Mikheeva,Buneva Buneva

doi:10.3390/biom9110741

Baranova Baranova, Nevinsky Nevinsky + Show 2 more

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https://doi.org/10.3390/biom9110741

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Abstract

It is known that intranuclear histones can be pernicious after entering to the extracellular space. In addition, the immunization of animals with exogenous histones leads to systemic inflammatory and toxic reactions. Abzymes—autoantibodies with enzymatic activities—are the distinctive feature of autoimmune diseases and they can be especially dangerous to humans. Here, electrophoretically homogeneous IgGs were isolated from sera of patients with multiple sclerosis (MS) by chromatography on several affinity sorbents. We present evidence that sera of all MS patients contain autoantibodies against histones and 73% of IgGs purified from the sera of 59 MS patients efficiently hydrolyze from one to five histones: H1, H2a, H2b, H3, and H4. The relative average efficiency of the histones hydrolysis was ~3.9-fold higher than that for healthy donors. The relative average activity of IgGs depends on the type of MS and decreased approximately in the following order: debut of MS, secondary progressive multiple sclerosis, remitting multiple sclerosis, remittent progressive multiple sclerosis. Similar to proteolytic abzymes of patients with several autoimmune diseases, histone-hydrolyzing IgGs from MS patients were inhibited in the presence of specific inhibitors of serine and of metal-dependent proteases, but an unexpected significant inhibition of the activity by inhibitors of thiol-like and especially acidic proteases was observed. Since IgGs can efficiently hydrolyze histones, a negative role of abzymes in the development of MS cannot be excluded.

Highlights

Abzymes (Abzs)—antibodies to chemically stable analogs to transition chemical states of different reactions—were well described
The relative average activity of IgGs depends on the type of MS and decreased approximately in the following order: debut of MS, secondary progressive multiple sclerosis, remitting multiple sclerosis, remittent progressive multiple sclerosis
To artificial abzymes against analogs of transition states of chemical reactions [1,2,3], naturally abzymes of autoimmune (AI) patients may be Abs synthesized by lymphocytes directly against different enzyme substrates acting as haptens and imitating transition states of catalytic reactions [1,2,3,4,5,6,7,8]

Summary

Introduction

Abzymes (Abzs)—antibodies to chemically stable analogs to transition chemical states of different reactions—were well described (reviewed in [1,2,3]). During three the last decades, it has become clear that autoantibodies (auto-Abs) from sera of patients with different autoimmune pathologies can possess enzymatic activities [3,4,5,6,7,8]. DNA, RNA, polysaccharides [11,12,13], oligopeptides, and proteins [14,15,16] are described from the sera of patients with several autoimmune diseases. Sera of some healthy humans contain abzymes with low proteolytic [14,15] and polysaccharide-hydrolyzing activities [13]. Germline Abs from healthy humans can, express auto-Abs with

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