Therapies for exacerbation of myasthenia gravis. The mechanism of action of intravenous high-dose immunoglobulin G.
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Biomedical subjects
Publications and source records attributed to B Ferrero.
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Total body irradiation (TBI) produces prolonged immunosuppression with rare side effects. We studied 12 thymectomized patients affected with chronic generalized severe myasthenia gravis. All patients had been totally or partially refractory to prolonged oral treatment with immunosuppressive drugs, and most had contra-indications for these drugs. Low-dose (1.8- to 2.3-Gy total dose) TBI was administered in single, 0.1-Gy doses, two to three times per week. TBI was well tolerated and was associated with objective clinical improvement in six patients, lasting more than 2 years in five. In addition, TBI produced a long-lasting lymphopenia with a pronounced decrease of T CD4+ lymphocytes; T CD8+ lymphocytes were almost unchanged over the 2 years of the study. CD16+ and CD20+ lymphocytes, after an initial decrease, increased above baseline. TBI was also associated with decreased anti-AChR antibody titer. The decrease of lymphocyte count and of anti-AChR antibody titer was more pronounced in the patients who improved, suggesting that lymphopenia and immunosuppression may have contributed to clinical improvement.
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BACKGROUND: In the last two decades increasing interest has been focused on the association between autoimmune polyneuropathies and high titers of anti-nervous serum autoantibodies. High titer of IgG anti-GM1 antibody could be detected in Guillain Barre' syndrome and in chronic painful axonal sensory immune-mediated polyneuropathy. The possible occurrence of anti-nervous autoantibodies in autoimmune diseases not limited to the nervous system is still under study. METHODS: We evaluated 29 patients with systemic lupus erythematosus (SLE), 19 with biopsy-proven renal involvement, 28 patients with mixed IgM-K/IgG polyclonal cryoglobulinaemia (18 with glomerulonephritis) and 19 with small-sized vessel ANCA-associated vasculitis (12 with renal involvement) by using a sensitive immunoenzyme method of autoantibody detection. RESULTS: Compared to controls (1/176+/-1/205; 1:204+/-1:103), we found a significant increase in plasma IgM and IgG anti-GM1 titers (1:643+/-1:531; 1:444+/-1:309) in SLE patients (p<0.0001). We also found IgM (1:3032+/-1:2844) and IgG (1:1560) anti-sulphatide titers to be higher than the control group (p<0.0001). Mean plasma IgM and IgG anti-GM1 titers of the cryoglobulinaemic patients were 1:524+/-1:403 and 1:501+/-1:415, respectively, once again higher than the controls (p<0.0001). Mean plasma IgM and IgG anti-sulphatide titers in this group were 1:1864+/-1:1189 and 1:1350 (p<0.0001). We found idiopathic systemic vasculitis patients to have significantly increased levels of anti-sulphatides IgG class autoantibodies (1:1400; p<0.0001). We found no correlation with the serologic markers for vasculitis or the clinical or histologic extent of renal involvement. Electrophysiologic studies revealed that in 38% of SLE patients (p<0.005), 61% of cryoglobulinaemic patients (p<0.01) and 42% of ANCA-related vasculitic patients (p<0.01) the abnormal titers of antineuronal antibodies were associated with clinical or subclinical evidence of neuropathy. CONCLUSIONS: In patients with systemic idiopathic or secondary vasculitis anti-GM1 and anti-sulphatide antibodies can frequently be found. Their presence should prompt an accurate neurological examination because these serologic abnormalities are significantly associated with neurologic, often subclinical, involvement. Antineuronal reactivity might be the epiphenomenon of primary phylogistic damage, which exposes normally segregated neuronal epitopes or be directly involved in triggering neurological injury.