Normal human immunoglobulin suppresses experimental myasthenia gravis in SCID mice

Serum IgM has been shown to participate in the control of IgG autoreactivit y in healthy subjects. We have recently shown that an immunoglobulin prepar ation of pooled normal human IgM (IVIgM) contains anti-idiotypic antibodies against disease-associated IgG autoantibodies in autoimmune patients and p rotects rats from experimental autoimmunity. The aim of the present study w as to asses the in vitro and in vivo immunomodulatory effects of IVIgM in c omparison with IgG, in SCID mice reconstituted with thymic cells from a mya sthenia gravis patient. Non-leaky SCID mice were injected i.p. with 60 x 10 (6) thymic cells from a patient with myasthenia gravis and 1 day later boos ted with 106 irradiated acetylcholine receptor (AchR)-expressing TE671 cell s. On days 14, 21 and 28, mice were treated with IVIgM or with equimolar am ounts of human serum albumin. The level of anti-AchR antibodies in the sera of three out of four IgM-treated animals was less than 1 nM. Further, ther e was a significant decrease in the loss of endplate AchR on the diaphragms of IgM-treated SCID mice. These findings indicate that pooled normal IgM e xerts an immunoregulatory role in experimental myasthenia gravis, and sugge sts that IgM may be considered as an alternative approach in the therapy of autommune diseases.