Myasthenia gravis with thymoma and pure red blood cell aplasia

A case of myasthenia gravis with histopathologic confirmation of spindle cell thymoma and pure red blood cell aplasia is reported. This is the twelfth case in the literature in which a simultaneous occurrence of all three disorders, with documented thymic pathology, is noted. Immunologic observations in this patient include an elevated acetylcholine receptor antibody and antinuclear antibody titer, agglutination of mouse red blood cells when combined with the patient's serum, and lack of inhibition of binding of radioactive erythropoietin to mouse red cell receptors when combined with the patient's serum. Although both myasthenia with thymoma and pure red blood cell aplasia may have a common immunologic denominator, our findings in this case indicate that inhibition of erythropoiesis is unrelated to erythropoietin receptor blockade. An alternative hypothesis is offered based on defective T-cell function.     

Myasthenia gravis induces the activation and maturation of lymphocytes in thymoma

The biological differences between lymphocytes separated from thymoma patients with myasthenia gravis (MG) and those separated from thymoma patients without MG was examined. We investigated whether lymphocytes in thymoma (Th-L) of patients with and without MG could react to interleukin-2 (IL-2) to develop cytolytic activity against K562 and lymphokine-activated killer (LAK) activity, and their phenotypic changes during incubation with IL-2. Sixteen thymoma patients who consisted of eight patients with MG and eight patients without MG were investigated. Th-L of all MG patients could react to IL-2 to develop LAK activity. Th-L of all of MG patients also developed cytolytic activity against K562 target cells. Cytolytic activity against K562 and LAK activity from Th-L of the MG patients were significantly higher than those from Th-L of the patients without MG (P<0.01,P<0.01). The proportions of CD3+ and CD4–/CD8+ cells of Th-L of MG patients increased significantly during the incubation period with IL-2 (P<0.05,P<0.05). The proportion of CD4+/CD8+ cells of Th-L of patients with MG decreased significantly (P<0.05) during incubation with IL-2. On the other hand, there was no significant phenotypic change in Th-L of the patients without MG. These results indicate that MG induces the functional and phenotypic activation and functional and phenotypic maturation of Th-L.     

Myasthenia gravis patients with thymus hyperplasia and myasthenia gravis patients with thymoma display different HLA associations

Thirty myasthenia gravis (MG) patients (9 with thymoma, 12 with thymus hyperplasia and 9 with thymic atrophy) and 181 Norwegian healthy controls were serologically typed for HLA-A, -B and -DR antigens and genomically typed for HLA-DQA1 and HLA-DQB1 alleles by probing in vitro amplified DNA with sequence-specific oligonucleotides. In patients with thymus hyperplasia the frequency of the DQB1*0201 allele was increased compared to controls (RR = 3.5, p less than 0.05), whereas among the patients with thymoma this allele was not observed (RR = 0.06, p less than 0.01). The frequencies of HLA-B8, -DR3 and -DQA1*0501, which are in strong linkage disequilibrium with DQB1*0201, were increased in patients with hyperplasia and reduced in patients with thymoma. The data suggest that different HLA genes predispose to two different forms of MG.     

Myasthenia gravis

The cause of the myasthenics' pathogenic autoantibody response against the muscle acetylcholine receptor is an intriguing puzzle involving the thymus and its epithelial tumours, and possibly a variety of cross-reacting epitopes. Another fascinating challenge is to find ways of selectively inhibiting this response in the patients.     

Myasthenia gravis and Werlhof's disease

A case of Werlhof's disease (immune thrombocytopenia) associated with myasthenia gravis is described. The two disorders developed within a few months of each other. The immunological and practical aspects of the association are discussed.     

Myasthenia gravis with thymoma is not associated with an increased incidence of non-muscle autoimmune disorders.

Three groups of thymectomized patients with myasthenia gravis (MG) were selected for study, 16 with thymoma, 16 with thymic atrophy and 32 with follicular hyperplasia of the thymus. All 16 patients with thymoma, 15/16 with thymus atrophy and 30/32 with follicular hyperplasia had AChR antibodies. Non-receptor muscle (CA) antibodies were found in sera of 15/16 patients with thymoma, 3/16 with thymus atrophy and in none of the sera from patients with follicular hyperplasia. There were 2 patients with thymoma and polymyositis, but none of the thymoma patients had rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) or other autoimmune disorders. Among the 32 patients with follicular hyperplasia of the thymus were 2 with SLE, 2 with RA and 1 with juvenile diabetes mellitus. In this study, there was an increased incidence of non-muscle autoimmune disorders among MG patients with follicular hyperplasia of the thymus but not among MG patients with thymoma.     

Microscopic thymoma and myasthenia gravis.

A rare case of microscopically sized thymoma is described in a 56 year old man suffering from myasthenia gravis. Histological examination of the surgically removed thymus showed the presence of several epithelial thymoma-like islands. As controls, 100 thymuses obtained from consecutive necropsies were sampled: 4% of these cases showed epithelial islands. This case is further proof that "microscopic thymoma" is a true pathological entity and suggests that every thymus removed from myasthenic patients in which there is no macroscopic evidence of thymoma should be examined microscopically on serial sections.     

Pseudooutbreak of cryptococcal meningitis.

A pseudooutbreak of cryptococcal meningitis was caused by the use of contaminated albumin solution used in the preparation of Papanicolaou-stained slides of cerebrospinal fluid. Organisms were seen in cytocentrifuge preparations, but not in India ink preparations of cerebrospinal fluid specimens. Cryptococcal antigen tests were positive and Cryptococcus neoformans was cultured from the albumin-treated cerebrospinal fluid specimens and from the albumin solution.     

Myasthenia gravis thymus: clinical, histological and culture correlations

This paper attempts to quantitate immunohistological changes in the myasthenia gravis (MG) thymus and to correlate them with clinical and culture parameters in 40 untreated young onset patients covering a wide range of durations and serum anti-acetylcholine receptor (AChR) antibody titers. Total cellularities of both the thymic cortex and the medulla declined significantly with age. There was some hyperplasia of subcapsular and of medullary epithelial cells, often at the expense of cortex. A combined index of all hyperplastic changes correlated significantly with serum anti-AChR titre. Otherwise histological indices, e.g. of germinal centres (GC) were largely unrelated to any clinical parameters, especially duration of symptoms. Specific anti-AChR synthesis in culture (very closely related to serum titer) correlated better with the medullary lymph node-type T-cell areas; these were more widely prevalent and MG-specific. In contrast, basal and mitogen-stimulated total IgG productivity followed the GC indices more closely. We propose that the variability of GC is due to their dependence on extraneous immune complexes, and we discuss whether they or the T-cell areas are primary or secondary abnormalities. Finally, we conclude that autosensitization in MG with thymic hyperplasia and neoplasia probably arises through separate mechanisms.