Seronegative myasthenia gravis
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It has been 20 years since Lindstrom et al. [1] reported the results of a binding assay for acetylcholine receptor (AChR) antibodies in patients with myasthenia gravis (MG). This assay has subsequently become a major tool in evaluating patients with known or suspected MG. In the original report of Lindstrom et al., 6% of patients with generalized MG and almost 30% of those with ocular myasthenia did not have elevated binding antibody levels. In subsequent reports, from 7 to 34% of patients with MG did not have elevated binding antibodies (Table 1). These patients without elevated AChR antibodies are referred to as having seronegative myasthenia gravis (SN-MG).
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Table 1. Frequency of seronegative MG
The clinical features of MG patients with elevated AChR antibodies (seropositive, SP-MG) and without elevated AChR antibodies (seronegative, SN-MG) are similar, although patients with SN-MG are more likely to have purely ocular myasthenia or milder disease (Table 1). As in SP-MG, an autoimmune process underlies SN-MG. Evidence supporting this includes the fact that patients with SN-MG improve after immunotherapy such as plasma exchange, immunosuppression, and thymectomy. [2-4] Abnormal neuromuscular transmission can be transferred to animals by injecting immunoglobulin from patients with SN-MG. [5-9] This immunoglobulin has direct blocking effects on neuromuscular transmission when applied in vitro to nerve-muscle preparations. [10]
Several factors may affect the frequency of SN-MG in published reports. The sensitivity of the assay has a marked effect on the proportion of patients in whom antibodies are detected. A less sensitive assay identifies fewer seropositive patients and the proportion of SN-MG is therefore greater. The duration of disease at the time the assay is performed may also influence the results. Patients may have normal AChR antibody levels within the first months of symptoms and elevated AChR antibodies thereafter (see below). Immunotherapy or thymectomy before assay …
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