Neutralization of IgG autoantibodies of autoimmune patients by IgM-enriched immunoglobulin preparations: implication for immunotherapy

Journal/Book: Z Rheumatol 1998; 57 Suppl. 1: 72 (P 111). 1998;

Abstract: INSERM U430 Hôpital Broussais Paris The last decade has witnessed major changes in paradigms on self-reactivity and significant advances in the understanding of the genetic molecular and cellular basis of autoimmune responses and their control. The structure and functions of "natural" antibodies i. e. antibodies circulating in normal individuals and produced in the absence of overt specific antigenic stimulation within and outside the immune system have been extensively studied. Normal polyspecific IgG (IVIg) prepared from plasma of healthy donors has been shown to be beneficial in the treatment of patients with autoimmune disorders. Considering the role of serum IgM in regulating the IgG autoreactivity we have assessed the immunomodulatory capacity of (i) pooled normal human IgM (IVIgM) purified from plasma of over 2500 healthy donors and of (ii) Pentaglobin(r) an IgM-enriched human intravenous immunoglobulin preparation which has been used in the treatment of several bacterial infectons concomitantly with antibiotics. We have shown that IVIgM and Pentaglobin(r) suppresses activity of IgG autoantibodies purified from the serum of patients with autoimmune diseases in vitro. We have examined the ability of Pentaglobin(r) to inhibit the autoantibody activity of anti-DNA antithyroglobulin and anti-FVIII autoantibodies purifed respectively from the sera of patients with systemic lupus erythematosus Hashimoto's thyroiditis and autoimmune disease with anti-FVIII antibodies. The inhibitory effect was greater or equivalent to that of IVIg on a molar basis. We demonstrate that IVIgM and Pentaglobin(r) contains anti-idiotypic antibodies directed against idiotypic determinants of autoantibodies in particular by showing that Sepharose-bound IVIgM selectively retained F(ab')2 fragments of IgG autoantibodies. ... le

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