[Immunologic and clinical aspects of food allergy].
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Antibody Formation↗
Biomedical subjects
G K Scadding
Publications and source records attributed to G K Scadding.
Myasthenia gravis. Pathogenesis and current concepts in management.
Myasthenia gravis is a disorder of autoimmunity in which neuromuscular transmission is impaired by autoantibodies to the acetylcholine receptor (AChR). There is evidence for more than one form of the disorder with differing genetic susceptibilities. The aetiology is unknown, but thymic involvement is suggested by abnormal histology and by the beneficial response of the disorder to thymectomy in more than two-thirds of patients. Thymectomy is indicated in most patients unless the symptoms are minimal or are confined to the extraocular muscles alone, or the patient is elderly. Thymectomy alone results in remission in about one-third of patients, but, in addition, most patients require symptomatic anticholinesterase drugs to prolong the action of acetylcholine at the muscle end-plate. Over-dosage of these drugs can also cause weakness. Immunosuppression with corticosteroids or azathioprine may also improve myasthenia; at present, these drugs are used mainly in patients who do not respond to thymectomy or in those patients considered unsuitable for operation. Plasma exchange can cause a rapid, though temporary, involvement in myasthenia, but it probably has no long term place in its treatment. Future therapy will probably involve specific immunotherapy, such as anti-idiotype antibodies.
Cholinesterase Inhibitors↗
Glomerulonephritis, thymoma and myasthenia gravis.
Three patients with myasthenia gravis, in whom a thymoma had been removed during total thymectomy four to 14 years earlier, developed glomerulonephritis presenting as the nephrotic syndrome. All had been treated previously by plasma exchange and were receiving azathioprine. Two were also taking prednisolone. Serum immune complexes containing IgM were present in all three. Renal histology showed either focal segmental glomerulosclerosis, minimal change lesion or focal proliferative glomerulonephritis. No immunoglobulin deposits were seen. Two patients lost their proteinuria on high dose corticosteroid therapy and their renal function improved. Glomerulonephritis occurred in nine per cent of patients with thymoma receiving immunosuppressive treatment with azathioprine for more than two years. We suggest that this treatment may be implicated in its aetiology.
Adult↗
Pathogenesis and treatment of myasthenia gravis.
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Acetylcholine↗
Acetylcholine receptor antibody synthesis by thymic lymphocytes: correlation with thymic histology.
Antiacetylcholine receptor antibody (anti-AChR) was spontaneously synthesized by cultured thymic tissue from 19 of 35 patients with myasthenia gravis. Two other thymus cultures produced antibody after stimulation by pokeweed mitogen. Antibody production correlated with histologic evidence of thymitis, long duration of symptoms, or high serum anti-AChR values. None of seven thymomas synthesized antibody in culture, but evidence suggested that there had been in vivo synthesis or trapping of anti-AChR. Clinical improvement after thymectomy, during the short period of study, did not correlate with synthesis rates of anti-AChR production by the removed thymus. The rates of anti-AChR production in culture were too low to suggest that the thymus is the major source of this antibody. Although we did not find a clear relationship between anti-AChR antibody and clinical state within 3 months of thymectomy, in a study of 25 nonimmunosuppressed, nonthymoma patients followed for 1 to 4 years, we found a significant correlation (p less than 0.05, Spearman Rank correlation) between fall in anti-AChR antibody and clinical improvement after thymectomy (unpublished observations).
Acetylcholine↗
Humoral immunity before and after thymectomy in myasthenia gravis.
Humoral immunity was studied in 10 patients with myasthenia gravis before thymectomy, in 15 different patients over 10 years after thymectomy, and in normal controls. Antibody titers to acetylcholine receptor were significantly (p less than 0.01) lower in the post-thymectomy group. However, other antibody titers to common viruses, and to Escherichia coli, and isohemagglutinins showed no significant change. Levels of IgM and IgE (with atopic subjects excluded) decreased following thymectomy (p less than 0.05). Autoantibodies persisted, apart from those directed against the acetylcholine receptor. The absence of any significant changes in humoral immunity after thymectomy for myasthenia gravis suggests that there is no generalized loss of helper T-cell function.
Adult↗
The immunological effects of thymectomy in myasthenia gravis.
Thymus-derived (T) lymphocytes in the peripheral blood and cellular immune function have been studied in ten patients with myasthenia gravis and in fifteen different myasthenic patients more than 10 years after thymectomy. The results were compared with those of a normal control population. The non-thymectomized myasthenic patients had normal T lymphocyte concentrations measured by rosetting with native sheep red cells. These patients also showed normal sensitization and recall of delayed hypersensitivity, phytohaemagglutinin (PHA) induced lymphocyte transformation and antibody-assisted (K cell) cytotoxicity; however, PHA-induced cytotoxicity was markedly reduced (P less than 0.001). The thymectomized group exhibited a lower mean percentage and absolute number of E-rosette-forming cells, which returned toward normal after in vitro treatment with thymosin. PHA-induced lymphocyte cytotoxicity, however, was normal in the patients who had undergone thymectomy, as were lymphocyte transformation, antibody-assisted cytotoxicity and sensitization to dinitrochlorobenzene (DNCB); there was a decrease in recall of established delayed hypersensitivity. Adult thymectomy in man, therefore, produces a partial and dissociated decrease in T cell responses and it is unlikely that the beneficial effect of this operation in myasthenia gravis is related to immunosuppression.
Adolescent↗
In-vitro synthesis of anti-acetylcholine-receptor antibody by thymic lymphocytes in myasthenia gravis.
Cultures of thymic tissue or thymic lymphocytes from nine patients undergoing thymectomy for myasthenia gravis were examined for evidence of anti-acetylcholine-receptor-antibody synthesis. One of four thymic tissues and three of five thymic lymphocyte preparations synthesised this antibody.
Acetylcholine↗
Myasthenia gravis: acetylcholine-receptor antibody titres after thymectomy.
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Antibodies↗
The in vitro effects of D-penicillamine upon anti-AChR production by thymic and peripheral blood lymphocytes from patients with myasthenia gravis.
D-Penicillamine added to lymphocyte cultures from myasthenia gravis patients infrequently and inconsistently stimulated anti-AChR production. This usually occurred in the presence of pokeweed mitogen (PWM), and often only at a single concentration of D-penicillamine which varied among patients. The change was typically paralleled by an increase in total IgG production of similar magnitude, suggesting that the effect was nonspecific. D-penicillamine did not affect AChR expression in cultured thymic adherent cells. These data provide no evidence that penicillamine induces myasthenia gravis by direct stimulation of anti-AChR antibody-producing cells.
Adolescent↗
The effect of endoscopic sinus surgery on asthma: management of patients with chronic rhinosinusitis, nasal polyposis, and asthma.
We attempted to determine the efficacy of endoscopic sinus surgery in adult patients with asthma and chronic rhinosinusitis or nasal polyposis. Fifty asthmatic patients from 17 to 74 years of age with a history of either chronic rhinosinusitis or nasal polyposis were examined. Sinonasal disease was confirmed endoscopically and with computerized tomography, and all had failed aggressive medical management of their sinonasal disease before undergoing endoscopic sinus surgery performed by the same surgeon in all cases. The following were compared for 12 months: preoperative and postoperative overall asthma control, peak flow measurements, asthma medication requirements, including the use of oral steroids, and hospitalizations for asthma. Twenty patients felt that their asthma control had improved postoperatively. Twenty per cent used less steroid inhaler, and 28% less bronchodilator inhaler. Of those 23 patients measuring peak flows, seven achieved higher levels and seven noted fewer dips and swings. Significant reductions in oral steroid requirements (p < 0.001) and hospitalization for asthma (p < 0.025) were also recorded postoperatively. Irrespective of whether the patient had chronic rhinosinusitis or nasal polyposis, both groups improved postoperatively. The commonest symptoms experienced by the group as whole and by the nasal polyposis patients were hyposmia and nasal obstruction. Postnasal discharge and headache were more important in the chronic rhinosinusitis group. Mean visual analog scores improved for all symptoms; in particular for nasal obstruction and sense of smell. Aggressive management of sinonasal pathology can improve asthma status. No major differences were recorded for outcomes when comparing patients with chronic rhinosinusitis or nasal polyposis; in particular there was no evidence for a worsening of asthma after nasal polypectomy.
Administration, Oral↗