Search

The antibodies against pre-synaptic membrane receptor (PsmR) and acetylcholine receptor (AChR) in serum samples of myasthenia gravis (MG) patients and healthy donors were tested by enzyme-linked immunosorbent assays (ELISA). The serum samples of eight MG patients with different autoantibodies and those of six healthy donors without these two kinds of autoantibodies were collected to investigate their effects on the peri-neurially recorded membrane currents at mouse motor nerve terminals. After inhibition of both fast and Ca(2+)-dependent K+ currents by tetra-ethylammonium (TEA), a positive wave was revealed, which was a balance of the slow K+(Ik,s) and Ca2+ currents (ICa). Application of anti-PsmR antibody negative MG sera and healthy donor sera, whether anti-AChR antibody positive or negative, did not affect the positive wave. However, the positive wave shifted to prolonged Ca(2+)-plateau when adding two of four anti-PsmR antibody positive serum samples from MG patients, indicating an inhibition of Ik,s by anti-PsmR antibody positive sera. Meanwhile, all serum samples derived from either patients or healthy donors did not affect INa.

Peripheral blood and bone marrow from seronegative and seropositive myasthenics were evaluated for antibody-secreting cells (ASC). Cells secreting antibody to acetylcholine receptor (AchR) and to presynaptic membrane receptor (prsmR) were counted using an immunospot assay. Immunoglobulin G (IgG) anti-AchR ASC were present in peripheral blood lymphocytes (PBL) from nine of 13 seronegative and nine of 12 seropositive myasthenics and in bone marrow lymphocytes (BML) from nine of 13 seronegative and eight of 12 seropositive myasthenics. The mean number of IgG anti-AchR ASC was lower for seronegative than for seropositive patients (P < 0.01 for PBL and P < 0.0001 for BML). In seropositive patients the mean number of IgG anti-AchR ASC was higher for BML than for PBL (P < 0.01); in seronegative patients it was not. IgG anti-prsmR ASC were detected in PBL from four of eight seronegative and six of eight seropositive myasthenics and in BML from three of eight seronegative and five of eight seropositive patients. The mean number of IgG-anti-prsmR ASC did not differ between seronegative and seropositive patients for PBL but for BML the value was higher for seropositive than for seronegative patients (P < 0.01). We conclude that seronegative myasthenia gravis is an autoimmune disease and that ASC to AchR and to prsmR are present both in the blood and the bone marrow in seronegative patients as in seropositive ones. A major difference between the groups lies in the significantly greater number of ASC found in the bone marrow in the seropositive cohort.

Serum anti-acetylcholine receptor antibodies (A AchR Ab) and anti-synaptic premembrane antibodies (A PrM Ab) were measured in 21 patients with absence epilepsy, 21 cases with benign childhood epilepsy with centro-temporal spikes (BCECTs) and 13 cases with atypical epilepsy. Respectively, in five (23.8%), eleven (51.2%) and eight (66.7%) of the above mentioned groups of patients both A AchR Ab and A PrM Ab were found.

Antibodies against acetylcholine receptor (AChR), a protein that binds to alpha-bungarotoxin (alpha-BuTx), are characteristic for myasthenia gravis (MG) and are considered to be of importance in the pathogenesis of the disease. Antibodies against a beta-BuTx binding protein, presynaptic membrane receptor (PsmR), have also been reported in most MG patients. We have analysed the specificity and cross-reactivity of antibodies to bovine AChR and PsmR in sera from 11 patients with MG. More than 90% of antibodies to PsmR were adsorbed specifically by PsmR conjugated affinity chromatography. Similarly, more than 90% of anti-AChR antibodies were absorbed by AChR conjugated affinity chromatography. Specificities of antibodies from affinity chromatography were also confirmed by ELISA and agarose isoelectric focusing. However, the antibodies to PsmR and AChR from MG patients' sera showed about 45-55% cross-reactivity, and there was a high correlation between serum levels of both antibodies. The demonstration of anti-PsmR antibodies could be important in documenting presynaptic damage and understanding the pathogenetic process in MG.

Myasthenia gravis (MG) is considered as an autoimmune disease of neuromuscular junction resulting from antibodies directed to acetylcholine receptors (AChR). We describe the use of beta-bungarotoxin (beta-BuTx) and alpha-bungarotoxin (alpha-BuTx) to capture their corresponding proteins from preparation of crude human muscle receptor. beta-BuTx binds to presynaptic membrane receptor (PsmR) of the whole receptor fraction, while alpha-BuTx binds to AchR. The captured proteins were used as antigen in ELISA to detect antibodies to PsmR and to AchR in sera from 82 Chinese patients with MG and in controls. In MG, antibodies to PsmR only were detected in 13%, to AchR only in 11% and both to PsmR and AchR in 54%. Only 3 of 50 patients with other neurological diseases and none of 50 healthy subjects had these antibodies. Specificity tests for antibodies showed that the detection systems which we used are specific and confident. No correlation was found between antibody levels and clinical status. The significance of the PsmR antibodies in the pathogenesis of MG is unknown. We suggest that myasthenia gravis is not only due to damage of the postsynaptic membrane, but of presynaptic structures as well.