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Biomedical subjects

A Basten

Publications and source records attributed to A Basten.

At least 145 records · Page 8Linked to original sources

Immune complexes in thrombocytopenic patients: cause or effect?

Immune complexes (ICs) in the serum of 43 patients with chronic idiopathic thrombocytopenic purpura (ITP) were measured by the C1q deviation assay during the active and inactive phases of the disease. An inverse relationship between platelet count and levels of ICs was demonstrated in all but one patient. To test whether this phenomenon was specific for chronic ITP, ICs were assayed in sera from two groups of control patients with thrombocytopenia. Goup 1 had thrombocytopenia due to recognized immune mechanisms while group 2 had thrombocytopenia secondary to non-immune mechanisms. In both these groups the degree of thrombocytopenia proved to be inversely proportional to IC levels, which was similar to the pattern observed in chronic ITP. The specificity of the assay for detection of ICs was confirmed by demonstrating a positivity rate of 65% in sera of patients with systemic lupus erythematosus, a known IC disease. On analysis the ICs were shown to have molecular weights in excess of 500,000 daltons and contain variable immunoglobulin classes. The findings implicate ICs in immune destruction of platelets both in chronic ITP (as has been suggested previously) and also in thrombocytopenia secondary to known immune mechanisms. In addition the association of ICs with non-immune thrombocytopenias is consistent with the hypothesis that platelets play an important role in clearance of ICs from the circulation, thereby protecting the vascular endothelium from damage.

Antigen-Antibody Complex↗

Current trends in the management of myasthenia gravis: plasmapheresis and immunosuppressive therapy.

In recent years a considerable body of evidence has accumulated to demonstrate autoimmune mechanisms in myasthenia gravis. This evidence has important implications for the aetiology, diagnosis and management of the disease. The primary abnormality in myasthenia gravis is related to the presence of antibody which reacts with the acetylcholine receptor. Measurement of this IgG antibody in the serum has become the most reliable diagnostic adjunct to the edrophonium test, and in an individual patient, the level of the serum antibody relates closely to the clinical indices. In cases of myasthenia where control with anticholinesterase drugs is unsatisfactory, methods to lower the antiacetylcholine receptor antibody are indicated: these may include thymectomy, immunosuppressive therapy of plasmapheresis. Two patients with very severe disease are described in whom all types of therapy were used and in whom survival depended ultimately on the use of plasmapheresis. These patients illustrate the importance of receptor antibody in the clinical manifestations of myasthenia gravis and in its management.

Acetylcholine↗

Nodular pulmonary amyloidosis associated with benign hypergammaglobulinemic purpura.

A 59-year-old woman, who had had benign hypergammaglobulinemic purpura for three years, developed a solitary amyloid nodule of the lung. The benign hypergammaglobulinemia was associated with an IgG band of restricted heterogeneity and IG2-IgG3 subclass containing complexes of intermediate size with rheumatoid factor activity. Serum levels of IgA and IgM were also increased. Autopsy after death from an unrelated cause revealed no amyloid in the remainder of the lungs or other organs and no evidence of lymphoproliferative disorder.

Amyloidosis↗

Thymoma and late onset mucocutaneous candidiasis associated with a plasma inhibitor of cell-mediated immune function.

A case is described of chronic mucocutaneous candidiasis in association with thymoma. A plasma inhibitor of certain in vitro tests of cell mediated immune function, both of autologous and of normal cells was isolated from the patient's blood and shown to be stable on heating to 56 degrees C for 1 hour and to freezing and thawing. Isolation of the active fraction of Sephadex G-200 suggested a m.w. of 50,000-65,000 daltons. Despite disappearance of the inhibitor after apparently curative radiotherapy, suggesting the tumour was the origin, the chronic mucocutaneous candidiasis persists. The association of plasma inhibitors of immune function, with and without thymoma and chronic mucocutaneous candidiasis is reviewed and the possible nature of the substance discussed.

Aged↗

Hereditary angioedema: lack of close linkage with markers on chromosome 6, with data on other markers.

Members of two Australian families with type A Hereditary Angioedema (HAE), having affected individuals in three generations, were typed for a large number of genetic marker systems in a search for close linkage with the locus controlling C1 inhibitor (C1 inh). The evidence from both families indicated lack of close linkage with HLA or with the loci for Bf and GLO on chromosome 6. Very close linkage was also excluded between the locus for C1 inh and the loci for 6PGD, PGM1 and MNSs. The other markers were not informative, but data on all systems showing variation are reported. The publication of similar data for other kindreds will help to determine lod scores for the probability of linkage between the C1 inh locus and loci controlling common protein polymorphisms. Linkage studies of this kind could establish whether the loci controlling type A and B HAE are identical or separate.

Adult↗

Strong linkage disequilibrium between HLA-Dw2 and and BfS in multiple sclerosis and in the normal population.

An increased frequency of the S allele of Properdin factor B (BfS) was found amongst 162 patients with multiple sclerosis (MS) compared with 470 normal controls. This increase was shown to be due to a strong linkage disequilibrium (LD) between BfS and HLA-Dw2 in 77 patients typed for both systems (delta = 3.84%, P = .0002). The same LD was demonstrated amongst 100 normal controls (delta = 2.24%, P = .0049) and 31 patients with idiopathic demyelination of the peripheral nervous system (IDPN). A total of 70 haplotypes with HLA-Dw2 were encountered (40 MS, seven IDPN and 23 normal controls) and all contained BfS. In the MS patient group, a much weaker association was noted between BfS and HLA-B7 suggesting either that the Bf locus is musch closer to the HLA-D than the HLA-B locus or (and) that HLA-D and Bf products selectively interact (perhaps on the surface of B lymphocytes) with evolutionary advantage or disadvantage resulting from certain allelic combinations. Strong associations between BfS1 and HLA-Bw21 (P = .0000) and BfF1 and HLA-B18 (P = .0001), both previously reported, were confirmed in the current study. No increase in the frequency of a glyoxalase (GLO) allele was found amongst the MS patients and no LD was encountered between HLA-Dw2 and a GLO allele. The possibility that the HLA-Dw2, BfS disequilibrium has resulted from a selective advantage conferred on the general community but at the expense of increasing susceptibility to MS should be considered.

Chromosome Mapping↗

T cell-dependent suppression of antibody production. I. Characteristics of suppressor T cells following tolerance induction.

Specific immunological tolerance was induced in adult CBA mice by a single injection of deaggregated human IgG (dHGG). Spleen cells taken 7 to 42 days later, produced consistent suppression of a DNP-HGG collaborative antibody response on adoptive transfer into heavily irradiated recipients. Noncentrifuged F(ab')2 fragments of HGG were as effective as dHGG in the production of suppressor cells. Suppression was antigen-specific since HGG-tolerant cells failed to abrogate either a DNP-keyhole limpet hemocyanin collaborative response or antibody production to the noncross-reactive antigen, horse erythrocytes. Pretreatment of the tolerant cell population with anti-Thy-1 serum and complement reversed the suppressive effect. However, purified tolerant T cells obtained by passage through nylon wool or anti-Ig columns were less effective than the original spleen cells in mediating suppression. Analysis of the cell types appearing in the column effluents indicated that the reduction in suppressive activity is best explained by retention of T cells rather than macrophages. Different T cell populations, however, were retained on the two types of columns. In the case of anti-Ig columns, these consisted of Ly-2,3+, Ia+ effector cells, whereas nylon wool columns caused depletion of Ly-1,2,3+ cells which are known to act as amplifiers of suppression. Suppression could not be explained in terms of delay in differentiation of antibody-forming cell precursors since the effect persisted for up to 15 days after transfer of tolerant cells. The demonstration of a reduction in serum anti-DNP and anti-HGG antibodies excluded the possibility of antibody production in sites other than the spleen. A role for anti-carrier antibody-antigen complexes in mediating the effector phase of suppression was rendered unlikely by the finding that the suppressive effect of tolerant cells persisted in the absence of detectable anti-HGG antibody production. Effector T cells mediating suppression in this system were shown to bear the phenotype Ia+, Ly-2,3+ as judged by the effect of pretreatment with appropriate antisera and complement. They were spleen-seeking, but were not detected in the thymus or recirculating lymphocyte pool. Adult thymectomy failed to cause a significant reduction in suppressive activity by tolerant spleen cells indicating that at least a major component of the immediate precursors is not of recent thymic origin.

Animals↗