Cases reported "Immune Complex Diseases"

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1/32. ceftizoxime-induced hemolysis due to immune complexes: case report and determination of the epitope responsible for immune complex-mediated hemolysis.

    BACKGROUND: Several occurrences of immune complex-mediated, cephalosporin-induced intravascular hemolysis have been reported. This report describes the first case of hemolytic anemia caused by an immune-complex mechanism associated with ceftizoxime and delineates the epitope responsible for hemolysis. CASE REPORT: The patient's serum was tested for antibody that reacted with five penicillins and 30 cephems (all types of cephalosporins) by using protocols to detect drug-adsorption and immune-complex mechanisms. The patient's antibody that formed immune complexes with ceftizoxime reacted with 10 of 30 cephems. These 10 drugs were classified as oxime-type cephalosporins, which have a common structural formula consisting of [(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetoamido] at the C7 position on 7-aminocephalosporinic acid with or without substitution at the C3 position. CONCLUSION: The patient's antibody recognized a common structure in 10 oxime-type cephalosporins, and immune complexes formed by the antibody specifically or nonspecifically bound to red cell membranes. Therefore, when intermittent antibiotic therapy is required, as in this case, care should be taken in antibiotic selection to avoid drug-induced hemolytic anemia. In addition, when this type of hemolysis is observed, tests for antibody that reacts by adsorption and immune-complex mechanisms should be performed against penicillins and cephems to select antibiotics not showing a cross-reaction.
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2/32. Treatment of refractory antibody mediated autoimmune disorders with an anti-CD20 monoclonal antibody (rituximab).

    BACKGROUND: Rituximab, a chimeric monoclonal anti-CD20 antibody, has recently been used for the treatment of refractory antibody mediated autoimmune diseases such as immune mediated thrombocytopenia and haemolytic anaemia. patients: Because of its novel mechanism of action, rituximab was used to treat three patients with refractory systemic antibody mediated autoimmune disorders. The first patient, a 71 year old woman with idiopathic type II mixed essential cryoglobulinaemia, had both dermatological and neurological manifestations with marked renal disease attributed to her cryoglobulinaemia. Patient 2, a 73 year old woman with Goodpasture's syndrome, was refractory to conventional treatment (cyclophosphamide, prednisone, plasmapheresis). She had persistent haemoptysis and haematuria and positive antiglomerular basement membrane antibodies. The third patient, a 75 year old man with primary biliary cirrhosis, myelodysplasia, and systemic immune complex vasculitis, had progressive renal insufficiency, a macular erythematous rash, and severe thrombocytopenia. RESULTS: Treatment with rituximab resolved all clinical and laboratory manifestations in the three patients. CONCLUSIONS: Rituximab may be an important therapeutic agent for the treatment of patients refractory or intolerant to corticosteroid or cytotoxic treatment, or both.
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3/32. Autologous immune complex nephritis associated with sickle cell trait: diagnosis of the haemoglobinopathy after renal structural and immunological studies.

    A renal tubular epithelial antigen (RTE)--anti-RTE autologous immune complex nephritis associated with sickle cell anaemia (SS) has been reported, but immune complex nephritis has never been described in patients with sickle cell trait (SA). During investigation of a child with "asymptomatic proteinuria" cryoprecipitable complexes of RTE-anti-RTE were detected in the serum and granular deposits of RTE, immunoglobulins, and complement localised on the glomerular basement membranes. Morphological and ultrastructural studies showed increased mesangial matrix, sickled red blood cells in the glomeruli and vessels, and tubular and interstitial abnormalities. These findings prompted haemoglobin electrophoretic studies, which showed previously undiagnosed haemoglobin SA in this patient and her family. These observations suggest that nephritis mediated by similar immunopathogenic mechanisms may be associated with SS and SA haemoglobinopathy. Under some conditions patients with sickle cell trait may experience haemodynamic and oxygenation abnormalities, which may be aetiological factors in the immune complex nephritis associated with SS disease.
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4/32. Necrotizing vasculitis: a circulating immune complex producing inflammatory skin lesions.

    A patient with acute necrotizing vasculitis is described in whom tests for circulating immune complexes were negative. The patient's serum injected intradermally produced lesions which closely resembled those occurring spontaneously. When the serum was fractionated, the skin-reactive fraction was found to be associated with IgG, but was of a higher molecular weight than normal IgG. Immunofluorescent studies showed that lesions induced by this active fraction contained IgG and complement in the epidermal basement membrane zone and within the small dermal vessels. We conclude that an immune complex of relatively low molecular weight is present in the active fractions, and capable of initiating the lesions of acute necrotizing vasculitis.
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5/32. nephrotic syndrome associated with fanconi syndrome. Immunopathogenic studies of tubulointerstitial nephritis with autologous immune-complex glomerulonephritis.

    The nature of renal lesions in a patient with simultaneous onset of the fanconi syndrome and nephrotic syndrome was investigated by immunologic studies of the patient's serum, cryoproteins, and renal tissue. Acute severe tubulointerstitial nephritis and generalized segmental glomerulonephritis were present. Renal tubular epithelial (RTE) antigen, IgG, and Clq were localized in the glomerull and proximal tubules. Cryoprecipitates containing RTE antigen and anti-RTE antigen were isolated from the patient's serum antibody to RTE antigen was detected in the serum of the patient. However, antibody to tubular basement membrane was not found in the cryoproteins or serum. The unusual simultaneous presentation of these two syndromes in our patient possibly represents a common etiology: tubular damage with release of RTE antigen and subsequent development of immune-complex glomerulonephritis mediated by renal tubular epithelial antigen and antibody to this antigen.
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6/32. C1q nephropathy: do C1q deposits have any prognostic significance in the nephrotic syndrome?

    C1q deposits are usually found in association with other complement components and immunoglobulins in proliferative glomerulonephritis and may predominate in systemic lupus erythematosus (SLE). We report the clinical outcome of four patients who developed a nephrotic syndrome associated with C1q nephropathy unrelated to SLE. On presentation the mean urinary protein loss was 6.8 g/24 h (range 4-10), and renal function impaired, mean serum creatinine 201 mumol/l (150-400). Over a mean follow up period of 6.5 years (1.7-19), all four patients improved, three spontaneously and one treated with steroids and cyclosporin, to a current urinary protein loss of 0.3 g/24 h (less than 0.2-0.9) and serum creatinine 98 mumol/l (68-115). C1q nephropathy was confirmed in each biopsy by conventional immunohistology. C1q deposits were demonstrated within the glomerular basement membrane of three biopsies and the mesangium in two samples. One patient had been categorized on light- and electron-microscopy as having mesangiocapillary glomerulonephritis, one membranous glomerulonephritis, one proliferative glomerulonephritis with focal segmental glomerulosclerosis, and one diffuse proliferative glomerulonephritis with both subendothelial and mesangial dense deposits. In view of the expected progressive nature of the underlying renal histopathological appearance, the presence of predominant C1q deposits would appear to be associated with a better clinical outcome.
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7/32. Acute immune complex disease associated with hepatitis. Etiopathogenic and immunopathologic studies of the renal lesion.

    Immune deposit glomerulonephritis has been associated with hepatitis b antigenemia. Immune complexes of this antigen and its antibody have been implicated in the pathogenesis of the renal disease. A boy had acute immune complex disease with glomerulitis in which cryoprecipitable complexes of HbsAg and its antibody were isolated from serum. HbsAg was concentrated in the cryoprecipitate and localized in a granular pattern along the glomerular basement membrane in association with immunoglobulins. Glomerular fixed antibody was eluted and shown to be directed against HbsAg. The level of antibody activity to HbsAg was higher in the eluate than the serum, suggesting immunopathogenic specificity of the antibody. The study demonstrates that the nephritis was mediated by immune complexes of HbsAg and its antibody, and the presence of immunoglobulin on the kidney did not represent trapping from the circulation.
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8/32. Immune-complex glomerulonephritis in a patient with mixed connective tissue disease.

    Renal involvement and hypocomplementemia in mixed connective tissue disease are reported to be rare. A patient is described here with mixed connective tissue disease and persistently low serum C'3 levels in whom renal insufficiency and nephrotic syndrome developed secondary to immune-complex glomerulonephritis. light microscopy of the renal biopsy specimen showed predominantly a membranous lesion. Immunofluorescent staining showed granular deposition along the basement membrane of immunoglobulin g, immunoglobulin m, fibrinogen and C3. Electron microscopy showed numerous electron-dense deposits along the glomerular capillary membrane and in the mesangium.
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9/32. Vascular disease in infective endocarditis. Report of immune-mediated events in skin and brain.

    A patient with subacute bacterial endocarditis, who had a prosthetic mitral valve, exhibited hypocomplementemia, mixed (IgG, IgM) cryoglobulinemia, and widespread dermal vasculitis with IgM deposited at the dermoepidermal junction. Postmortem findings included immune-complex glomerulonephritis and deposits of IgG in the choroid plexus. These findings are consistent with a generalized vasculitis, which may be mediated by circulating immune complexes; basement membrane localization of immune complexes to the skin and choroid plexus appears not to be specific for systemic lupus erythematosus, as has been previously thought, but may represent the general phenomenon of immune-mediated pathogenesis.
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10/32. Evidence of both anti-GBM and immune complex mediated pathogenesis in the initial phase of Goodpasture's syndrome.

    A 19 year old women presented with pulmonary hemorrhage, rapidly progressive glomerulonephritis and antiglomerular basement membrane antibody in her serum. In the initial phase of the disease a double layered linear deposit of IgG was seen on the glomerular capillary basement membrane together with a finely granular or focal and lumpy single layer deposit of C3 and numerous small subepithelial electron dense deposits. These findings are suggestive of the simultaneous occurrence of anti-GBM and immune complex glomerulonephritis.
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