Autoimmune reactivity of IgM acquired after oxidation

Omersel, Jasna; Avberšek-Lužnik, Ivica; Grabnar, Pegi Ahlin; Kveder, T; Rozman, B; Božič, Borut

doi:10.1179/174329211x13190184351680

Cited by 8 publications

(12 citation statements)

References 40 publications

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“…IgG from apparently healthy donors was oxidized as previously described 7,10 with some modifications. Briefly, 250 ml of IgG sample aliquots were exposed to direct current (6 mA; voltage range 4.0-5.0 V) for 60 seconds on a current/voltage generator (E5263A-E5291A Module, Agilent Technologies, Santa Clara, CA, USA) using graphite stick electrodes (99.995% graphite rod, 3 mm diameter; 150 mm length; Sigma-Aldrich, St. Louis, MO, USA).…”

Section: Igg Oxidationmentioning

confidence: 99%

“…4 From a micro-scale perspective, altered antibody specificity and increased immunoreactivity to self-antigens was reported to occur due to a wide range of different factors, such as oxidative stress (reactive-oxygen species (ROS)), hemin, chemical agents/metabolites (hypochlorite (HOCl), peroxynitrite, urea), low pH, metal catalyzed-(Fe 2þ ) and electrooxidation. [5][6][7][8][9] Electro-oxidation of normally protective immunoglobulin (Ig)G and IgM isolated from healthy blood donors resulted in increased binding of oxidized antibodies to b2-glycoprotein I (b2GPI). 7,10 b2GPI, a plasma protein consisting of 326 amino acids arranged into five domains, is one of the main cofactors in antiphospholipid syndrome (APS).…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8][9] Electro-oxidation of normally protective immunoglobulin (Ig)G and IgM isolated from healthy blood donors resulted in increased binding of oxidized antibodies to b2-glycoprotein I (b2GPI). 7,10 b2GPI, a plasma protein consisting of 326 amino acids arranged into five domains, is one of the main cofactors in antiphospholipid syndrome (APS). 11 Antibodies binding to b2GPI (anti-b2GPI) are a heterogenic group of autoantibodies differing in mechanisms of action, 12,13 epitope binding 11,14 and avidity.…”

Section: Introductionmentioning

confidence: 99%

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Oxidatively altered IgG with increased immunoreactivity to β2-glycoprotein I and its peptide clusters influence human coronary artery endothelial cells

Artenjak

Omersel

Grabnar

et al. 2015

Lupus

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Oxidative stress has been shown to play a role in modifying antibodies in favor of higher auto-immunoreactivity. We studied the immunoreactivity of oxidized IgG (oxIgG) to β2-glycoprotein I (β2GPI), six peptide sequences corresponding to amino acid clusters on its different domains, to determine their effects on human coronary artery endothelial cells (HCAEC). Human IgG was purified from seven donors, electro-oxidized and checked for immunoreactivity and avidity to β2GPI and to peptides by ELISA. Conformational stability and antibody-antigen complex formation of oxIgG was analyzed by fluorescence spectroscopy and dynamic light scattering. Resting and activated sub-confluent HCAEC were stimulated with oxIgG or IgG. Secreted cytokines were measured by ELISA. Immunoreactivity of seven oxIgG samples increased to 7.5-fold against β2GPI and to 3.8-fold against six peptides as compared to IgG. oxIgG showed low avidity "properties." Conformational changes and exposure of protein hydrophobic regions were confirmed by an elevation in fluorescence (2.4- to 5.0-fold) on bis-ANS dye binding to oxIgG. oxIgG significantly elevated the release of GROα and IL-8 in resting and activated states of HCAEC. Oxidation alters IgG in favor of autoreactivity toward whole β2GPI and corresponding peptides on different domains of β2GPI and could lead to dysfunction of arterial endothelium by upregulation of chemokines.

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Section: Igg Oxidationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Oxidatively altered IgG with increased immunoreactivity to β2-glycoprotein I and its peptide clusters influence human coronary artery endothelial cells

Artenjak

Omersel

Grabnar

et al. 2015

Lupus

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“…[45][46][47] β2GPI, one of the main pathologically relevant antigens in antiphospholipid syndrome, was reported to be recognized by oxidatively altered IgG/IgM. 47,48 Peptide binding to TiO 2 NTs has been used predominantly for studying the increase of cell adhesion and osteogenic gene expression 22,23,49 as well as for soft tissue interactions 24 and local delivery of antimicrobial peptides. 50 A hexapeptide motif was found to bind electrostatically to titanium surfaces, with potential important osteogenic consequences.…”

Section: Introductionmentioning

confidence: 99%

Binding of plasma proteins to titanium dioxide nanotubes with different diameters

Kulkarni

Flašker

Lokar

et al. 2015

IJN

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Titanium and titanium alloys are considered to be one of the most applicable materials in medical devices because of their suitable properties, most importantly high corrosion resistance and the specific combination of strength with biocompatibility. In order to improve the biocompatibility of titanium surfaces, the current report initially focuses on specifying the topography of titanium dioxide (TiO 2 ) nanotubes (NTs) by electrochemical anodization. The zeta potential (ζ-potential) of NTs showed a negative value and confirmed the agreement between the measured and theoretically predicted dependence of ζ-potential on salt concentration, whereby the absolute value of ζ-potential diminished with increasing salt concentrations. We investigated binding of various plasma proteins with different sizes and charges using the bicinchoninic acid assay and immunofluorescence microscopy. Results showed effective and comparatively higher protein binding to NTs with 100 nm diameters (compared to 50 or 15 nm). We also showed a dose-dependent effect of serum amyloid A protein binding to NTs. These results and theoretical calculations of total available surface area for binding of proteins indicate that the largest surface area (also considering the NT lengths) is available for 100 nm NTs, with decreasing surface area for 50 and 15 nm NTs. These current investigations will have an impact on increasing the binding ability of biomedical devices in the body leading to increased durability of biomedical devices.

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“…Size exclusion chromatography was carried out using Sephacryl S-300 HR, as matrix on a 16 mm × 100 cm column (16/100 XK, Pharmacia Biotech, Uppsala, Sweden) in order to separate β 2GPI from proteoglycan 4 (PRG4) in the 1st peaks with a fractionation range for globular proteins from 10 to 1500 kDa [ 20 ]. The 1st peaks from several β 2GPI isolations were collected and concentrated with Amicon Ultra centrifugation filters from regenerated cellulose with MWCO lower than 10 kDa (Millipore, Carrigtwohill Co., Cork, Ireland) at 2000 ×g.…”

Section: Methodsmentioning

confidence: 99%

Optimization of Unnickedβ2-Glycoprotein I and High Avidity Anti-β2-Glycoprotein I Antibodies Isolation

Artenjak

Leonardi

Križaj

et al. 2014

Journal of Immunology Research

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Patient biological material for isolation of β2-glycoprotein I (β2GPI) and high avidity IgG anti-β2-glycoprotein I antibodies (HAv anti-β2GPI) dictates its full utilization. The aim of our study was to evaluate/improve procedures for isolation of unnicked β2GPI and HAv aβ2GPI to gain unmodified proteins in higher yields/purity. Isolation of β2GPI from plasma was a stepwise procedure combining nonspecific and specific methods. For isolation of polyclonal HAv aβ2GPI affinity chromatographies with immobilized protein G and human β2GPI were used. The unknown protein found during isolation was identified by liquid chromatography electrospray ionization mass spectrometry and the nonredundant National Center for Biotechnology Information database. The average mass of the isolated unnicked purified β2GPI increased from 6.56 mg to 9.94 mg. In the optimized isolation procedure the high molecular weight protein (proteoglycan 4) was successfully separated from β2GPI in the 1st peaks with size exclusion chromatography. The average efficiency of the isolation procedure for polyclonal HAv anti-β2GPI from different matrixes was 13.8%, as determined by our in-house anti-β2GPI ELISA. We modified the in-house isolation and purification procedures of unnicked β2GPI and HAv anti-β2GPI, improving the purity of antigen and antibodies as well as increasing the number of tests routinely performed with the in-house ELISA by ~50%.

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Autoimmune reactivity of IgM acquired after oxidation

Cited by 8 publications

References 40 publications

Oxidatively altered IgG with increased immunoreactivity to β2-glycoprotein I and its peptide clusters influence human coronary artery endothelial cells

Oxidatively altered IgG with increased immunoreactivity to β2-glycoprotein I and its peptide clusters influence human coronary artery endothelial cells

Binding of plasma proteins to titanium dioxide nanotubes with different diameters

Optimization of Unnickedβ2-Glycoprotein I and High Avidity Anti-β2-Glycoprotein I Antibodies Isolation

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