Pooled normal human polyspecific IgM contains neutralising anti-idiotypes to IgG autoantibodies of autoimmune patients and protects from experimental autoimmune disease

Hurez, Vincent; Kazatchkine, Michel D.; Ramanathan, Sheela; Vassilev, Tchavdar; Pashov, Anastas; Basuyaux, B.; Kozak, Y. de; Bellon, B; Kaveri, Srini V.

doi:10.1016/s0165-2478(97)88987-0

Cited by 21 publications

(26 citation statements)

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“…Previous studies have shown that IgM autoantibodies can regulate the natural autoantibody activity of IgG through idiotypic complementarity. Purified IgM could also modulate autoimmune disorders (31). Nevertheless, our results show clearly that IgM Abs do not neutralize or disturb IgG response against brain Ags.…”

Section: Discussionmentioning

confidence: 62%

Distortion of the Self-Reactive IgG Antibody Repertoire in Multiple Sclerosis as a New Diagnostic Tool

Lefranc¹,

Almeras²,

Dubucquoi³

et al. 2004

The Journal of Immunology

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To date, none of the myelin-associated Ag targets definitively discriminates between the immune response observed in multiple sclerosis (MS) patients and healthy subjects. However, it has been shown recently that analysis of global immune Ab profiles such as natural autoantibody reactivities can help to distinguish between normal individuals and patients suffering from various immune diseases. The aim of our study was to compare the global IgG immune response against brain self-Ags in sera from 82 MS patients and 27 healthy subjects. The analysis of the immune profiles was performed by Western blotting, and data were subjected to linear discriminant analysis. Particular patterns of IgG reactivity were found in healthy subjects, Sjögren patients, and MS patients. Moreover, this approach separated the three clinical forms of MS with a high concordance rate with the clinical data (κ value, 77.8%). Our study suggests, for the first time, that serum IgG Ab repertoires are able to distinguish MS patients. In addition, our data suggest that patterns of IgG reactivity could model the pathological processes underlying the various forms of MS. Further characterization of such discriminant Ags could provide useful information regarding their potent role in pathogenesis or regulatory processes in MS.

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Section: Discussionmentioning

confidence: 62%

Distortion of the Self-Reactive IgG Antibody Repertoire in Multiple Sclerosis as a New Diagnostic Tool

Lefranc¹,

Almeras²,

Dubucquoi³

et al. 2004

The Journal of Immunology

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“…Normal human IgM purified from the pooled plasma of more than 2,500 healthy donors was obtained from S. V. K. (28). The purity of IgM was more than 90% as confirmed by SDS͞PAGE.…”

Section: Methodsmentioning

confidence: 99%

Human monoclonal antibodies reactive to oligodendrocytes promote remyelination in a model of multiple sclerosis

Warrington

Asakura

Bieber

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

237

204

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Promoting remyelination, a major goal of an effective treatment for demyelinating diseases, has the potential to protect vulnerable axons, increase conduction velocity, and improve neurologic deficits. Strategies to promote remyelination have focused on transplanting oligodendrocytes (OLs) or recruiting endogenous myelinating cells with trophic factors. Ig-based therapies, routinely used to treat a variety of neurological and autoimmune diseases, underlie our approach to enhance remyelination. We isolated two human mAbs directed against OL surface antigens that promoted significant remyelination in a virusmediated model of multiple sclerosis. Four additional OL-binding human mAbs did not promote remyelination. Both human mAbs were as effective as human i.v. Ig, a treatment shown to have efficacy in multiple sclerosis, and bound to the surface of human OLs suggesting a direct effect of the mAbs on the cells responsible for myelination. Alternatively, targeting human mAbs to areas of central nervous system (CNS) pathology may facilitate the opsonization of myelin debris, allowing repair to proceed. Human mAbs were isolated from the sera of individuals with a form of monoclonal gammopathy. These individuals carry a high level of monoclonal protein in their blood without detriment, lending support to the belief that administration of these mAbs as a therapy would be safe. Our results are (i) consistent with the hypothesis that CNS-reactive mAbs, part of the normal Ig repertoire in humans, may help repair and protect the CNS from pathogenic immune injury, and (ii) further challenge the premise that Abs that bind OLs are necessarily pathogenic. E nhancement of remyelination and protection from axonal injury are important therapeutic goals in the treatment of inflammatory demyelinating central nervous system (CNS) disorders such as multiple sclerosis (MS). Remyelination in MS plaques can occur, but is limited (1, 2) even though oligodendrocyte (OL) progenitors are present in the adult (3, 4). A number of therapeutic strategies to promote remyelination have been tested in experimental animals. Transplantation of OLs (5) or their progenitors (6) into demyelinated tissue produces new myelin. Transplanted OL progenitors also can remyelinate demyelinated lesions in the adult CNS (7) and migrate toward an area of damage when placed in close proximity to the lesion (8). Unresolved issues remain concerning the survival of transplanted OL progenitors in the intact adult CNS and their ability to target to areas of myelin pathology (9). However, if CNS lesions are surgically approachable and axons are still intact, transplantation of glial cells may be a viable therapy for improving functional performance (10).The in vitro administration of growth or trophic factors induces the expansion of OL progenitors (11, 12) or promotes mature OLs to dedifferentiate and subsequently reinitiate a program of myelination (13,14). The in vivo administration of trophic factors via genetically engineered fibroblasts to the injured CNS promotes ax...

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“…The presence of cross-reactive idiotope(s) among humans is believed to be the basis for the reported beneficial effect in autoimmune disease of intravenous IgG. The reported success of such therapy [26][27][28][29][30][31][32][33] indicates that the interaction between idiotypic (Ab1) and anti-idiotype (Ab2) in intravenous IgG can regulate autoimmune responses. It is of interest that anti-idiotypic antibodies to an autoantigen PDC-E2 were apparently present as immune complexes with anti-PDC-E2, which, because they did not dissociate during purification of anti-PDC-E2, may be of high affinity; in contrast, anti-idiotypic antibodies to an extrinsic antigen tetanus toxoid were ''unmasked'' by the removal of antitetanus, and thus may be of lower affinity.…”

Section: Discussionmentioning

confidence: 99%

Anti–Idiotypic Antibodies to Anti-Pdc–E2 in Primary Biliary Cirrhosis and Normal Subjects

1999

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Anti-idiotypic antibodies may regulate the immune system and influence pathogenic autoimmunity. We investigated idiotype-anti-idiotype interactions in sera of patients with primary biliary cirrhosis (PBC), normal subjects and animals immunized with pyruvate dehydrogenase complex (PDC) or its derivatives. IgG autoantibody to the E2 subunit of PDC (PDC-E2) was derived by affinity-purification from sera of 12 patients with PBC, and F(ab) 2 was prepared (anti-PDC-E2-F[ab] 2 ). This was used as a reactant by enzyme-linked immunosorbent assay (ELISA) with sera from patients with PBC, normal subjects, or immunized animals. Results were that IgG antibody to anti-PDC-E2-F(ab) 2 was detectable at low concentration in 12 PBC sera (mean optical density [OD] ؎ SD: 1.02 ؎ 0.26), and also in 19 normal sera (mean OD ؎ SD: 0.97 ؎ 0.35) using a serum dilution of 1:20; background OD was 0.09 to 0.10, whereas antisera from animals immunized with PDC or PDC-E2 were nonreactive. There was a significant inverse correlation (r ‫؍‬ ؊.59, P ‫؍‬ .04) between the levels of anti-PDC-E2 in PBC sera (but not normal sera), and anti-idiotypic antibody reactive with anti-PDC-E2-F(ab) 2 . Anti-idiotypic antibody existed as a complex with anti-PDC-E2, because the removal of anti-PDC-E2 from serum resulted in decreased reactivity to anti-PDC-E2-F(ab) 2 . Reactivity between PDC-E2 and anti-PDC-E2 from PBC serum was not inhibited by normal sera, indicating that anti-idiotypic antibody from normal sera with anti-PDC-E2 reacts with the framework of F(ab) rather than the paratope. The conclusions are that PBC and normal sera contain IgG class anti-idiotypic antibodies to anti-PDC-E2, the characteristic autoantibody in PBC. Anti-PDC-E2 in immunized animals does not contain an idiotype cross-reactive with human anti-PDC-E2. Anti-idiotypic antibody in PBC is complexed with anti-PDC-E2 and in part accounts for immune complexes demonstrable in PBC. Anti-idiotypic antibody in PBC may regulate levels of anti-PDC-E2. (HEPATOLOGY 1999;29:624-631.)

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Pooled normal human polyspecific IgM contains neutralising anti-idiotypes to IgG autoantibodies of autoimmune patients and protects from experimental autoimmune disease

Cited by 21 publications

References 0 publications

Distortion of the Self-Reactive IgG Antibody Repertoire in Multiple Sclerosis as a New Diagnostic Tool

Distortion of the Self-Reactive IgG Antibody Repertoire in Multiple Sclerosis as a New Diagnostic Tool

Human monoclonal antibodies reactive to oligodendrocytes promote remyelination in a model of multiple sclerosis

Anti–Idiotypic Antibodies to Anti-Pdc–E2 in Primary Biliary Cirrhosis and Normal Subjects

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