Substrate specificity of IgGs with peroxidase and oxidoreductase activities from sera of patients with systemic lupus erythematosus and multiple sclerosis

Abstract

The analysis of IgGs to protect humans from oxidative stress through oxidation of harmful compounds was carried out. We have compared here for the first time peroxidase (in the presence of H 2 O 2 ) and oxidoreductase (in the absence of H 2 O 2 ) activities of IgGs from sera of healthy humans and patients with systemic lupus erythematosus (SLE) and multiple sclerosis (MS). In addition, substrate specificity of SLE and MS IgG preparations in the oxidation of different compounds was analyzed: 2,2′azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 3,3′-diaminobenzidine (DAB), homovanillic acid (HVA), o-phenylenediamine (OPD), α-naphthol, 3-amino-9ethylcarbazole (AEC), p-hydroquinone (pHQ), and adrenaline. IgGs of healthy humans and SLE and MS patients oxidized DAB, ABTS, and OPD due to their peroxidase and oxidoreductase activities, while other compounds were substrates of IgGs only in the presence of H 2 O 2 : adrenaline was not oxidized by both activities of IgGs. The average SLE IgGs peroxidase activity increased statistically significant in comparison with abzymes from healthy humans in the order (-fold): OPD (1.2) < DAB (1.7) < α-naphtol (2.2) ≤ AEC (2.4) < ABTS (4.5) < 5-ASA (10.6), while with oxidoreductase activity: OPD (1.8) ≤ DAB (2.1-fold) < ABTS (5.0). Only HVA was oxidized by IgGs with peroxidase activity of healthy donors faster than by SLE (1.3-fold) and MS abzymes (2.4-fold). In the oxidation of several substrates, only three IgGs of MS patients were used. The data speak of a tendency to increase the peroxidase and oxidoreductase activities of MS IgGs in comparison with healthy donors, but to a lesser extent: OPD (1.1 to 1.2-fold) ≤ ABTS (1.2 to 1.8-fold). It was shown that development of SLE and MS leads to increase in peroxidase and oxidoreductase activities of IgGs toward most of classical substrates. Thus, abzymes can serve as an additional factor of reactive oxygen species detoxification protecting of patients with SLE and MS from some harmful compounds somewhat better than healthy peoples.

Immunoglobulins with Non-Canonical Functions in Inflammatory and Autoimmune Disease States

“…As can be seen from the data presented, AIDs are accompanied by the formation of abzymes with the broadest repertoire of catalytic activities. Catalytic Abs hydrolyzing DNA, RNA, oligonucleotides, proteins, peptides and oligosaccharides and possessing oxidoreductase activity are formed in these diseases [ 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 ]. It should be noted that the highest level of catalytic activity of abzymes is found in such severe autoimmune pathologies as systemic lupus erythematosus (SLE) and multiple sclerosis (MS) [ 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 ].…”

Increase in Autoantibodies-Abzymes with Peroxidase and Oxidoreductase Activities in Experimental Autoimmune Encephalomyelitis Mice during the Development of EAE Pathology

“…Average peroxidase and oxidoreductase activities of SLE IgGs were statistically significantly higher in comparison with abzymes from healthy humans. IgGs of MS patients demonstrated these activities more elevated than that for healthy volunteers but lower than for SLE abzymes [39]. The data obtained speak in favor that abzymes can serve as an additional blood factor of reactive oxygen species detoxification.…”

“…Using different methods, we have shown convincing evidence that H 2 O 2 -dependent peroxidase and H 2 O 2 -independent oxidoreductase activities are intrinsic to IgGs of healthy humans and animals [31][32][33][34][35][36][37][38]. We have then compared redox activities of IgGs from sera of healthy humans and patients with SLE and MS [39]. Average peroxidase and oxidoreductase activities of SLE IgGs were statistically significantly higher in comparison with abzymes from healthy humans.…”

Six catalytic activities and cytotoxicity of immunoglobulin G and secretory immunoglobulin A from human milk

“…Peroxidase Activities Assay. Measurements of the IgG and sIgA H 2 O 2 -dependent peroxidase activities were carried using 25 mM potassium-phosphate (pH 6.8), 10 mM H 2 O 2 , 0.2 mg/mL 3,3′-diaminobenzidine (molecular mass 214.27 g/mol), and 6.6 μM IgG or sIgA as in Tolmacheva et al (2018Tolmacheva et al ( , 2019. The reaction mixtures (0.2 mL) were performed in multiwell plates in the dark at 23°C depending on the relative activity of Abs for 0.5 to 20 min.…”

“…These preparations of IgG and sIgA were used as a second negative control. It was shown previously that IgG from the blood of SLE patients possess increased cytotoxicity (Kozyr et al, 1998;Nevinsky and Buneva, 2003) and catalyze the hydrolysis of DNA and RNA (Andrievskaya et al, 2000(Andrievskaya et al, , 2002, proteins (Bezuglova et al, 2011(Bezuglova et al, , 2012, and oligosaccharides (Savel'ev et al, 1999) as well as have redox activity (Tolmacheva et al, 2019). As a positive control, we used an equimolar mixture of IgG preparations from the blood of 7 SLE (sle-IgG mix ) patients, showing high activity in all the above chemical reactions.…”