1/83. Paraproteinemic variety of pure red cell aplasia: immunological studies in 1 patient.A case of adult pure red cell aplasia (PRCA) with a serum IgG inhibitor to erythropoiesis and an IgG lambda M component is presented. The study of lymphocyte populations revealed a slight but definite decrease of E and EA rosettes, with dissociation between E rosettes and PHA blastic transformation of blood lymphocytes and increase of membrane IgM-bearing lymphocytes. The relationship between PRCA and paraproteinemia is discussed: it is suggested that the serum M component may derive from an immunological unbalance between T and B lymphocytes. Since a survey of the literature reveals 5 similar cases, it is suggested that paraproteinemia may be the hallmark of a particular variety of chronic PRCA 'type 1'.- - - - - - - - - - ranking = 1keywords = membrane (Clic here for more details about this article) |
2/83. Antiepiligrin (laminin 5) cicatricial pemphigoid associated with an underlying gastric carcinoma producing laminin 5.Although bullous pemphigoid and cicatricial pemphigoid are sometimes associated with malignancy, it remains uncertain whether such an association is pathogenetically related or just a coincidence attributable to the advanced age of the patients. We report a 61-year-old patient with antiepiligrin (laminin 5) cicatricial pemphigoid (AeCP) associated with an advanced gastric carcinoma. The gastric carcinoma cells in this patient were shown to produce laminin 5 by immunofluorescence microscopy, and the patient's serum contained autoantibodies directed against laminin 5 on immunoprecipitation. Furthermore, the blistering symptoms and the titre of antibasement membrane zone antibodies coordinately changed with the resection and subsequent relapse of the gastric cancer. These observations suggest that the gastric carcinoma producing laminin 5 may have induced the production of autoantibodies to this laminin, which were pathogenic to the skin and mucous membranes in this patient. This report demonstrates a link between this autoimmune subepithelial blistering disease and malignancy. It is of interest and potential great importance to examine other cases of AeCP for such a potential association.- - - - - - - - - - ranking = 2keywords = membrane (Clic here for more details about this article) |
3/83. Defective apoptosis due to a point mutation in the death domain of CD95 associated with autoimmune lymphoproliferative syndrome, T-cell lymphoma, and Hodgkin's disease.apoptosis via CD95 and its ligand is an important mechanism that prevents uncontrolled proliferation of activated lymphocytes and regulates lymphocyte homeostasis. The apoptosis receptor CD95 is a transmembrane protein with an intracellular domain well conserved between CD95 and tumor necrosis factor receptor I, another apoptosis-inducing protein. Because of its functional importance, this domain was designated the death domain. We describe the molecular analysis of the CD95 death domain in a family with autoimmune lymphoproliferative syndrome (Canale-Smith syndrome), T-cell lymphoma, and Hodgkin's disease. A functional defect in apoptosis was detected in cells from the index patient, a 5-year-old girl suffering from Canale-Smith syndrome and a T-cell lymphoma, as well as in her father, who had a history of splenomegaly and mild hemolysis, and her paternal uncle who had been cured of Hodgkin's disease (HD). Expansion of double-negative T cells (CD4-CD8-) was only seen in the index patient. All family members with a functional defect in apoptosis were heterozygous for a point mutation in the death domain of CD95 (A1009G, E256G). We conclude that, within the same family, a defect in apoptosis due to a mutation in the CD95 death domain can be associated with diverse clinical phenotypes, including mild, reversible symptoms and different malignancies.- - - - - - - - - - ranking = 1keywords = membrane (Clic here for more details about this article) |
4/83. Drug-induced linear iga bullous dermatosis probably induced by furosemide.linear iga bullous dermatosis (LABD) is an autoimmune disease, characterized by linear deposition of IgA along the basement membrane zone. Drug-induced LABD is rare but increasing in frequency. A new case of drug-induced LABD associated with the administration of furosemide is described.- - - - - - - - - - ranking = 1keywords = membrane (Clic here for more details about this article) |
5/83. Immunoadsorption as a tool for the immunomodulation of the humoral and cellular immune system in autoimmune disease.Immunoadsorption onto staphylococcal protein a is a newly developed semiselective extracorporeal adsorption technique for immunoglobulins applied in patients suffering from severe autoimmune disease. Its effect on the humoral and cellular immune system was investigated using standard immunological assays. The elimination capacity for total IgG and IgG subclasses 1, 2, and 4 was more than 90% but for subclass IgG3 varied between 30 and 90%. autoantibodies, e.g., anti-dsDNA, anti-glomerular basement membrane (anti-GBM), anti-cardiolipin, and anti-human leukocyte antigen (anti-HLA) antibodies, were eliminated in comparable amounts. The affinity of protein A for circulating immune complexes (CIC) was 300 times greater than for soluble IgG. HLA-II expression on monocytes and T lymphocytes was reduced over time during repeated IAs (IA). The number of activated T lymphocytes declined while the percentage of naive T cells increased. A diminished CD4/CD8 ratio normalized during IA treatment. These results indicate that IA actively modulates the humoral as well as the cellular immune system in addition to its immunoglobulin reducing effect.- - - - - - - - - - ranking = 1keywords = membrane (Clic here for more details about this article) |
6/83. A case of acquired autoimmune bullous disease associated with IgM macroglobulinaemia.A variety of autoimmune bullous dermatoses have been reported to develop in association with lymphoproliferative disorders. We report a patient with IgM macroglobulinaemia, who presented with a skin fragility similar to but somewhat milder than that seen in epidermolysis bullosa acquisita. Immunofluorescence detected circulating IgM autoantibodies reacting with the basement membrane zone, which reacted predominantly with dermal side of 1 M NaCl-split skin. immunoblotting of the epidermal and dermal extracts with the patient's serum showed no specific reactivity. Further studies are needed to identify the antigenic molecules responsible for the IgM deposition.- - - - - - - - - - ranking = 1keywords = membrane (Clic here for more details about this article) |
7/83. Erythroblastic synartesis: an auto-immune dyserythropoiesis.Erythroblastic synartesis is a rare form of acquired dyserythropoiesis, first described by Breton-Gorius et al in 1973. This syndrome is characterized by the presence of septate-like membrane junctions and "glove finger" invaginations between erythroblasts, which are very tightly linked together. This phenomenon, responsible for ineffective erythropoiesis, leads to an isolated severe anemia with reticulocytopenia. In the following report, we describe 3 new cases of erythroblastic synartesis associated with dysimmunity and monoclonal gammapathy. In all cases, the diagnosis was suggested by characteristic morphological appearance of bone marrow smears, and further confirmed by electron microscopy. Ultrastructural examination of abnormal erythroblast clusters showed that these cells were closely approximated with characteristic intercellular membrane junctions. The pathogenesis of the dyserythropoiesis was modeled in vitro using crossed erythroblast cultures and immunoelectron microscopy: when cultured in the presence of autologous serum, the erythroblasts from the patients displayed synartesis, whereas these disappeared when cultured in normal serum. Moreover, synartesis of normal erythroblasts were induced by the patient IgG fraction. Immunogold labeling showed that the monoclonal IgG were detected in, and restricted to, the synartesis. A discrete monoclonal plasmacytosis was also found in the patient bone marrow. The adhesion receptor CD36 appeared to be concentrated in the junctions, suggesting that it might be involved in the synartesis. These experiments indicated that a monoclonal serum immunoglobulin (IgG in the present cases) directed at erythroblast membrane antigen was responsible for the erythroblast abnormalities. Specific therapy of the underlying lymphoproliferation was followed by complete remission of the anemia in these cases.- - - - - - - - - - ranking = 3keywords = membrane (Clic here for more details about this article) |
8/83. Unique immunobullous disease in a child with a predominantly IgA response to three desmosomal proteins.We report the case of a 15-year-old girl who presented at 11 years of age with an interesting, acquired and, to our knowledge, unique blistering disease. It involved both skin and mucous membranes with extensive oral and periungual lesions, clinically resembling paraneoplastic pemphigus. skin biopsy showed an inflammatory cell infiltrate in the upper dermis with numerous leucocytoclastic nuclear fragments, neutrophilic papillary microabscesses and a small subepidermal bulla. Direct and indirect immunofluorescence studies showed marked intercellular staining with IgA and less prominent staining with IgG. Granular deposition of IgA and, to a lesser extent IgG and C3, was also seen along the basement membrane zone. immunoblotting and enzyme-linked immunosorbent assay studies showed both IgG and IgA antibodies to desmocollin, desmoglein 3 and desmoplakin. However, despite extensive investigation, no underlying neoplasm was found. Treatment with dapsone and sulphapyridine proved ineffective but methylprednisolone and azathioprine have reduced the blistering. We believe that this patient is unique for her combination of IgA and IgG antibodies to desmoplakin, desmocollin and desmoglein 3, although further studies may provide further clarification.- - - - - - - - - - ranking = 2keywords = membrane (Clic here for more details about this article) |
9/83. Ocular involvement in IgA-epidermolysis bullosa acquisita.epidermolysis bullosa acquisita (EBA) is an autoimmune bullous disease with frequent ocular involvement, but visual loss is rare. In contrast, EBA patients with predominant IgA autoantibodies more frequently develop severe ocular involvement, which tends to be refractory to therapy. We report two patients with 'IgA-EBA' with ocular involvement. Both initially presented with a generalized bullous disease, and direct immunofluorescence microscopy demonstrated IgA in the basement membrane zone of the skin, and in the conjunctiva and cornea of patient 1. On salt-split patient skin, IgA was found predominantly on the dermal side of the artificial split in both patients. Direct immunoelectron microscopy demonstrated IgA below the lamina densa in close association with the anchoring fibrils in both patients. In patient 1, who had a prolonged course of the disease, the skin disorder responded well to treatment with cyclosporin, but the ocular involvement ended in bilateral blindness despite repeated surgical treatment. In patient 2, the blister formation and scarring conjunctivitis was stopped by a combination of prednisolone and colchicine. These patients show that in subepithelial blistering diseases, early delineation of disease nosology is critical to detect subtypes with severe ocular involvement such as 'IgA-EBA'. In addition, colchicine may be a valuable alternative in the treatment of EBA with ocular involvement.- - - - - - - - - - ranking = 1keywords = membrane (Clic here for more details about this article) |
10/83. Late development of antidesmoglein 1 antibodies in pemphigus vulgaris: correlation with disease progression.The coexistence of antidesmoglein 3 (Dsg3) and antidesmoglein 1 (Dsg1) autoantibodies is well described in patients with pemphigus vulgaris (PV); however, there is little evidence of sequential development of these two autoantibodies. Autoantibody responses to Dsg3 and Dsg1 were studied in seven PV patients over time by enzyme-linked immunosorbent assay, using baculovirus expressed recombinant fusion proteins. All patients had anti-Dsg3 IgG antibodies at presentation. Two patients developed anti-Dsg1 later in the course of the disease. The transition in autoantibody profile was associated with disease progression to generalized PV involving mucous membranes and skin in both patients; one patient initially presented with a predominantly mucosal phenotype, the other with herpetiform pemphigus-like features. These findings demonstrate that there is an extension of autoimmune response from anti-Dsg3 only to both anti-Dsg3 and anti-Dsg1 in some patients, which is associated with an alteration in clinical expression in PV.- - - - - - - - - - ranking = 1keywords = membrane (Clic here for more details about this article) |
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