Studies on natural antibodiesand autoantibodies

Avraméas, Stratis; Dighiero, Guillaume; Lymberi, Peggy; Guilbert, B

doi:10.1016/s0769-2625(83)80061-0

Cited by 74 publications

(52 citation statements)

References 20 publications

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“…In the last 10 yr antibodies against selfcomponents have been described, although at relatively low concentrations, in sera of apparently healthy animals and humans (3,(31)(32)(33) proteins of the keratin (34,35) and the vimentin (36) types, actin, tubulin, and spectrin (e.g., references 1, 2, and 37) and a variety of soluble cytoplasmic and secretory proteins such as thyroglobulin, myoglobin, albumin, and transferrin (33). Most of these natural autoantibodies examined have been found to belong to the IgM class (1,3,36,38).…”

Section: Resultsmentioning

confidence: 99%

“…Recently, evidence has accumulated for the occurrence of spontaneous antibodies, i.e., antibodies formed without intentional immunization in healthy individuals, which are commonly interpreted as autoantibodies (e.g., references [1][2][3]. In some cases the antigenic targets appear to be constituents of intracellular structures such as actin, tubulin, spectrin, myoglobin, vimentin, and keratin.…”

Section: Introductionmentioning

confidence: 99%

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High concentrations of antibodies to xanthine oxidase in human and animal sera. Molecular characterization.

Bruder¹,

Jarasch²,

Heid³

1984

J. Clin. Invest.

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Abstract. The widespread occurrence of antibodies (IgG) specific to xanthine oxidase in both normal (nonimmune) human and animal sera, and in antisera raised against a diversity of unrelated antigens is described. A study of sera from 81 humans revealed that xanthine oxidase-specific IgG represents a high proportion (1-8%) of total IgG. No obvious correlation to pathological events or symptoms of disease could be found. These xanthine oxidase-specific antibodies could be isolated by immunoaffinity chromatography on purified human or bovine xanthine oxidase and showed specific binding to the enzyme polypeptide of M, 155,000 in immunoblotting experiments. By immunofluorescence microscopy they displayed the same cell type-specific reaction as experimentally induced antibodies, i.e., the staining of lactating mammary gland epithelium and capillary endothelium.The naturally occurring xanthine oxidase-specific antibodies consisted of polyclonal IgG of various subclasses. F(ab')2 preparations gave immune-reactions identical. to those of IgG. The human xanthine oxidasespecific IgG cross-reacted with the bovine enzyme and both human and animal antibodies partially inhibited its activity. The xanthine oxidase activity of human milk lipid globules and supernatant fractions from various human tissues was extremely low when compared with that of the bovine antigen. The enzyme protein, however, was effectively precipitated from these sources by both the human and bovine antibodies.We suggest that the exceptionally high concentrations

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High concentrations of antibodies to xanthine oxidase in human and animal sera. Molecular characterization.

Bruder¹,

Jarasch²,

Heid³

1984

J. Clin. Invest.

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“…Almost all of the human autoimmune diseases are characterized by the generation of Natural Antibodies (NA) [40][41][42][43][44]. Identifying those antibodies is the cornerstone for the diagnosis of autoimmunity in humans [45][46][47][48][49][50].…”

Section: Journal Of Molecular Biomarkers and Diagnosismentioning

confidence: 99%

Identification of Circulating Natural Antibodies against Endogenous Mediators in the Peripheral Blood Sera of Patients with Osteoarthritis of the Knee: A New Diagnostic Frontier

Savitskaya¹,

Duarte²,

Marin³

et al. 2012

J Mol Biomark Diagn

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Introduction: The presence of NA against EM regarding specificity and have gained increasing attention in proteome analysis for diagnosis, developing, monitoring and effective treatment of osteoarthritis of the knee (kOA). An understanding of the various regulatory systems controlling blood vessel growth, inflammation and pain in the join should lead to help explain kOA disease progression. To investigate the specific presence of NA (IgM, IgG, IgA) against EM (BK, AII, VEGF, bFGF) in the sera of kOA patients and control and to correlate this with process of joint destruction. Methods:In this study novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive ELISA method to directly detect immune complexes (NA-EM) in humans. Following this procedure, we examined variations in the levels of natural antibodies recognized a panel of self-antigens in the sera from healthy individuals and kOA patients. Blood samples were obtained from 250 patients with symptomatic kOA and 250 ages, sex-matched healthy individuals.Results: NA against EM was detected with novel ELISA assay in the sera of kOA patients as well as in the sera of control. At time of inclusion kOA patients (100%) had significantly higher BK-IgG levels relative to normal sera. The over expression BK-IgG were positively associated with destructive changes (KL>4; r=0.75; p<0.005). KOA patients in whom KL scores progress rapidly tend to have higher BK-IgG levels at all time point. Serum BK-IgG over expression in kOA patients were positively associated with destructive changes (KL>4; r=0.75; p<0.005). Elevated BK-IgG was significantly correlated with VAS (r=0.85; p<0.0001) and loss of functions (r=0.69; p<0.0003) in kOA patients. Affinity chromatography yielded EM-specific NA from the sera of healthy individuals and kOA patients. Conclusions:We showed that EM represents a group of novel self-antigens which are targeted by NA from kOA patients. Circulating BK-IgG in the sera has been proposed as a sensitive and specific marker of diagnosing kOA at early stages of the disease. Our results have potential applications for controlling unwanted angiogenesis, inflammation, pain and future response to therapy in kOA patients. Osteoarthritis of the knee (kOA) can be a progressive disabling disease, which results from the pathological imbalance of degradative and reparative processes, with concomitant inflammatory changes [2]. The clinical features of kOA include pain, stiffness, reduced motion, swelling, crepitus, and deformity [3][4][5]. Journal of Molecular Biomarkers & DiagnosisSeveral factors are considered for the pathogenesis of kOA [6][7][8][9][10][11][12][13][14]. Complicated path biological interactions between the KallikreinKinin System (KKS), the Rennin-Angiotensin (RAS), angiogenesis and natural immunity could contribute to joint destruction in the disease process of kOA [15][16][17][18][19]. It is also likely that biomarkers will be used in conjunction with imaging in order to establish stage of disease,...

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“…It is estimated that 30-80% of non-selected natural antibodies (Abs) are polyreactive [1][2][3][4]. A high level of polyreactivity is found after polyclonal B cell activation with lipopolysaccharide (LPS) [2,3,5].…”

Section: Introductionmentioning

confidence: 99%

Polyreactive Binding of Antibodies Generated by Polyclonal B Cell Activation. II. Crossreactive and Monospecific Antibodies can be Generated from an Identical Ig Rearrangement by Differential Glycosylation

1997

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Fernández C, Alarcón-Riquelme ME, Sverremark E. Polyreactive Binding of Antibodies Generated by Polyclonal B Cell Activation. II. Crossreactive and Monospecific Antibodies can be Generated from an Identical Ig Rearrangement by Differential Glycosylation. Scand J Immunol 1997;45:240-247 In this work the authors tested the hypothesis that differential glycosylation may be one of the mechanisms by which B cells could be able to produce monospecific or polyreactive antibodies flexibly. The same genetic information will be used in both situations. To prove this hypothesis the authors used mice transgenic for the SP6 (m þ k) hybridoma cell line producing monoclonal antibodies (MoAbs) with specificity for the hapten 2,4,6-trinitrophenyl (TNP). In these animals most cells in the periphery express exclusively the transgene SP6. To obtain polyreactive antibodies (Abs) spleen cells from transgenic animals were stimulated in vitro with lipopolysaccharide (LPS). The authors used LPS derived B cell blasts to produce a hybridoma cell collection. A high proportion of the monoclonal antibodies were found to bind to TNP and to crossreact with unrelated antigens. Endogenous immunoglobulins (lgs) were not responsible for crossreactivity since the crossreactive clones only expressed the transgene products. This was demonstrated by polymerase chain reaction (PCR) amplification of cDNA and by sequencing analysis of the PCR products. The nucleotide sequences of the expressed mono-and crossreactive genes were identical to the sequences of the rearranged V H and V K SP6 which undoubtedly demonstrates that crossreactive Igs are derived from the same rearrangement and also that no mutations in the V H or V K or in the CDR3 could account for the observed crossreactivity. It is also shown here that the crossreactive antibodies bear the idiotype Id 20-5 characteristic of SP6 binding Abs. Crossreactive monoclonal antibodies were found to be slightly more glycosylated than the TNP-monospecific Abs. Furthermore, binding to TNP was not influenced by treatment with tunicamycin, an inhibitor of glycosylation, while, in the same molecule, other types of binding were considerably reduced. This supports the hypothesis of the importance of glycosylation in polyreactivity. INTRODUCTIONIt is estimated that 30-80% of non-selected natural antibodies (Abs) are polyreactive [1][2][3][4]. A high level of polyreactivity is found after polyclonal B cell activation with lipopolysaccharide (LPS) [2,3,5]. It is uncertain whether the polyreactive Abs induced after LPS stimulation are different from the Abs in the specific pool or if the polyreactive Abs are modified specific Abs.In the accompanying article [6], we have shown elsewhere that 2-4% of the monoclonal antibodies (MoAbs) originated after stimulation with LPS bound to the carbohydrate dextran B512 (Dx), and that the vast majority of them were crossreactive with the unrelated antigen bovine serum albumin (BSA). We also demonstrated that crossreactive Abs were more sensitive to deglycosylation promoted b...

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Studies on natural antibodiesand autoantibodies

Cited by 74 publications

References 20 publications

High concentrations of antibodies to xanthine oxidase in human and animal sera. Molecular characterization.

High concentrations of antibodies to xanthine oxidase in human and animal sera. Molecular characterization.

Identification of Circulating Natural Antibodies against Endogenous Mediators in the Peripheral Blood Sera of Patients with Osteoarthritis of the Knee: A New Diagnostic Frontier

Polyreactive Binding of Antibodies Generated by Polyclonal B Cell Activation. II. Crossreactive and Monospecific Antibodies can be Generated from an Identical Ig Rearrangement by Differential Glycosylation

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