No abstract

Clinical myasthenia gravis has been reported in an increased frequency after bone marrow grafting. The number of bone marrow transplanted patients making IgG autoantibodies directed against the autoantigens cardiolipin, SS-B (La) and thyroglobulin was found to be significantly lower as compared to the autoantigen acetylcholine receptor protein. The occurrence of antibodies to single-stranded DNA was found in a lower frequency than acetylcholine receptor antibodies but the difference was not statistically significant. Antibodies to cardiolipin were frequently observed prior to grafting. The G1m1,2 and G3m5 phenotype frequency did not differ in individuals who developed receptor antibodies from that found in the normal population. Analysis of HLA antigens in this patient group revealed no association to HLA B8/DR3 or B35/DR1. This may indicate that the etiology of myasthenia gravis induced by bone marrow grafting differs as compared with the spontaneous form of myasthenia gravis and the penicillamine-induced disease.

In sera from 4 of 25,000 individuals tested for antibodies against streptococci, extremely high antideoxyribonuclease B titers ( > 10(6) U/ml) were found. Two of the cases were diagnosed as monoclonal gammopathies. The M-components were shown to possess the anti-deoxyribonuclease B activity. The other two cases were diagnosed as relapsing erysipelas. The high serum titers of deoxyribonuclease B antibodies were accompanied by a very inflammatory reactivity in the patients' sera and by an oligopolyclonal pattern of immunoglobulin G. In routine diagnoses of streptococcal infections with the anti-deoxyribonuclease B test, patients with extremely high serum titers should be examined for the possible occurrence of gammopathies.

The effect of nuclear stimulators and inhibitors on the nuclear contents of nucleoplasmic antigens (ENA) was studied by the indirect immunofluorescence technique. Human autoimmune sera, one reacting with RNase-A-sensitive and one with RNase-A-resistant components of ENA in the passive haemagglutination test, were used as indicators of the RNP and Sm antigens, respectively. Phytohaemagglutinin and concanavalin A both caused an accumulation of these antigens in normal blood lymphocytes. With pokeweed mitogen, staphylococcal protein A, or purified protein derivative the accumulation was apparently restricted to B cells, alpha-amanitine, 10 microgram/ml, prevented the mitogen-induced accumulation of RNP in normal human blood lymphocytes and reduced the contents of this antigen in several lymphoblastoid cell lines and in HeLa cells but did not significantly affect the contents of Sm antigen in any of these cell types. The experimental results suggest that the RNP and Sm nucleoplasmic antigens are normal rapid-phase reactants integrated in physiological nuclear mechanisms rather than inert structural constituents of the nuclear matrix or the products of a latent virus.

The nucleoplasmic autoantigens RNP and Sm are of particular interest because of their associations with certain symptoms of mixed connective tissue disease and systemic lupus erythematosus. The RNP is generally thought to be a ribonucleoprotein and there is evidence that its RNA may be single-stranded. Experiments presented in this report are in support of the concept that the Sm-antigen may also be an RNA protein. Purified Sm-anti-Sm precipitates were shown to have high RNA contents and treatment of Sm-antigen with RNAase in a hypotonic medium strongly reduced in antigenicity. The latter effect indicates that the Sm-antigen may in contrast to the RNP contain double-stranded RNA, a possibility also suggested by the finding that the Sm-antigen was soluble in 2 M LiCl. The Sm-antigen was found further to differ from RNP in being selectively absorbed in BD-Sephadex, while RNP remained active in the supernatant. Cytochemical studies involving stimulation and inhibition experiments with lectins and RNA polymerase inhibitors showed that the Sm-antigen was, in distinction to RNP, sensitive to rifampicin but not to alpha-amanitine. This suggests that the RNAs of the nucleoplasmic antigens may be synthesized by different RNA polymerases.