1/114. A fatal case of autoimmune thrombocytopenia with an IgM anti-GPIb/IX following one antigen mismatched unrelated donor bone marrow transplantation.We report the case of a 32-year-old patient with ALL who developed autoimmune thrombocytopenia 2 months following allogeneic bone marrow transplantation. An IgM autoantibody against the platelet glycoprotein Ib/IX complex was observed. Treatment with high-dose steroids and intravenous immunoglobulin g failed to produce any benefit and the thrombocytopenia led to fatal gastrointestinal haemorrhage. The possible factors contributing to post-allograft thrombocytopenia and potential management strategies are discussed.- - - - - - - - - - ranking = 1keywords = complex (Clic here for more details about this article) |
2/114. Immunoablative high-dose cyclophosphamide without stem cell rescue in paraneoplastic pemphigus: report of a case and review of this new therapy for severe autoimmune disease.Paraneoplastic pemphigus (PNP) is a refractory and life-threatening autoimmune mucocutaneous disease. We have recently reported the effectiveness and safety of ablative intravenous cyclophosphamide (200 mg/kg daily over 4 days) without stem cell rescue in patients with refractory autoimmune diseases including systemic lupus erythematosus, autoimmune cytopenias, chronic inflammatory demyelinating polyneuropathy, and aplastic anemia. We report chronic lymphocytic leukemia-associated PNP in a patient who presented with extensive and debilitating painful oral ulcerations and received ablative therapy. The patient tolerated the regimen well and showed a slow but sustained improvement despite persistence of the underlying neoplasm. Eighteen months after therapy, the oral ulcerations were almost completely healed and the circulating autoantibodies became negative. Currently, the patient remains on cyclosporine and a low dose of prednisone. This provides further evidence for the efficacy and safety of this regimen in the management of severe autoimmune diseases including PNP.- - - - - - - - - - ranking = 0.35172538489779keywords = neoplasm (Clic here for more details about this article) |
3/114. 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 = complex (Clic here for more details about this article) |
4/114. High anti-golgi autoantibody levels: an early sign of autoimmune disease?IgG anti-Golgi complex antibodies were detected by means of indirect immunofluorescence in the sera of five patients during routine investigation for suspected systemic autoimmune disease. The typical picture of paranuclear fluorescence was observed on the HEp-2 cell line and in tissue sections; anti-Golgi specificity was confirmed on the HEp-2 cells using the immunoperoxidase method. The phenomenon was transient in three patients with a probable viral infection and whose sera had low titre antibodies; however, it was persistent and in high concentration in the other two who, five years later, developed an autoimmune disease. Only in the sera of these last two patients were specific bands of 123, 72, 46, 37 and 26 kilodaltons found by the immunoblotting technique on cytoplasmic extracts. Although the detection of anti-Golgi autoantibodies is rare, and may represent a transitory epiphenomenon in patients with a viral infection, their presence in high titre in the absence of a clear clinical picture may constitute an early sign of systemic autoimmune disease.- - - - - - - - - - ranking = 1keywords = complex (Clic here for more details about this article) |
5/114. 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 = 0.35172538489779keywords = neoplasm (Clic here for more details about this article) |
6/114. Autoimmune liver disease in patients with neoplastic diseases.BACKGROUND: Development of de novo autoimmune liver disease has not been well documented in patients with malignant diseases. methods/RESULTS: In this paper we report on a series of six patients with neoplastic disorders who acquired liver disease with autoimmune features. Five patients had suffered from haematological neoplasms and one from colonic cancer. In two patients, liver disease was detected at the time of presentation with malignancy. In the remaining four, all of whom were successfully treated for malignancies, features of liver disease presented at intervals 24-72 months after the cancer diagnosis. Twelve liver specimens (11 biopsies and one hepatectomy specimen) were obtained at time intervals of 1-76 months after initial presentation of neoplastic disease. Biopsies from three patients showed features of hepatitis (one acute, one sub-acute, one chronic). Two patients had histological features suggestive of an overlap syndrome (one autoimmune hepatitis/primary biliary cirrhosis, one autoimmune hepatitis/primary sclerosing cholangitis). The sixth patient had features of autoimmune cholangiopathy. All but one responded well to steroid therapy with complete clinical and biochemical remission obtained 4 weeks to 8 months after steroid introduction. We discuss briefly possible aetiologies of autoimmune liver disease in these patients. CONCLUSIONS: Autoimmune liver disease may be precipitated by therapy for neoplastic disease or malignant disease itself. The unusually heterogeneous clinicopathological findings in this group as well as the response to treatment support the concept of a wide spectrum of manifestations of autoimmune liver disease. The results may also suggest that autoimmune liver disease may be possibly added to the list of paraneoplastic syndromes. Further prospective studies are required to confirm a causal association and to determine whether the mechanisms involved are disease- or treatment-related.- - - - - - - - - - ranking = 0.35172538489779keywords = neoplasm (Clic here for more details about this article) |
7/114. classification, clinical manifestations, and immunopathological mechanisms of the epithelial variant of paraneoplastic autoimmune multiorgan syndrome: a reappraisal of paraneoplastic pemphigus.BACKGROUND: Recent studies suggest that paraneoplastic pemphigus (PNP) is a heterogeneous autoimmune syndrome involving several internal organs and that the pathophysiological mechanisms mediating cutaneous, mucosal, and internal lesions are not limited to autoantibodies targeting adhesion molecules. OBJECTIVE: To classify the diverse mucocutaneous and respiratory presentations of PNP and characterize the effectors of humoral and cellular autoimmunity mediating epithelial tissue damage. methods: We examined 3 patients manifesting the lichen planus pemphigoideslike subtype of PNP. A combination of standard immunohistochemical techniques, enzyme-linked immunosorbent assay with desmoglein (DSG) baculoproteins, and an immunoprecipitation assay were used to characterize effectors of humoral and cellular autoimmunity in patients with PNP and in neonatal wild-type and DSG3-knockout mice with PNP phenotype induced by passive transfer of patients' IgGs. RESULTS: In addition to the known "PNP antigenic complex," epithelial targets recognized by PNP antibodies included 240-, 150-, 130-, 95-, 80-, 70-, 66-, and 40/42-kd proteins but excluded DSG1 and DSG3. In addition to skin and the epithelium lining upper digestive and respiratory tract mucosa, deposits of autoantibodies were found in kidney, urinary bladder, and smooth as well as striated muscle. Autoreactive cellular cytotoxicity was mediated by CD8( ) cytotoxic T lymphocytes, CD56( ) natural killer cells, and CD68( ) monocytes/macrophages. Inducible nitric oxide synthase was visualized both in activated effectors of cellular cytotoxicity and their targets. Keratin 14-positive basal epithelial cells sloughed from the large airways and obstructed small airways. CONCLUSIONS: The paraneoplastic disease of epithelial adhesion known as PNP in fact represents only 1 manifestation of a heterogeneous autoimmune syndrome in which patients, in addition to small airway occlusion and deposition of autoantibodies in different organs, may display a spectrum of at least 5 different clinical and immunopathological mucocutaneous variants (ie, pemphiguslike, pemphigoidlike, erythema multiforme-like, graft-vs-host disease-like, and lichen planus-like). We suggest that the more encompassing term "paraneoplastic autoimmune multiorgan syndrome," or PAMS, be applied. The pathophysiological mechanisms of PAMS involve both humoral and cellular autoimmunity responses. Epithelial cell membrane antigens other than DSG1 or DSG3 are targeted by effectors of PAMS autoimmunity. apoptosis of damaged basal cells mediates epithelial clefting, and respiratory failure results possibly from obstruction of small airways with sloughed epithelial cells.- - - - - - - - - - ranking = 1keywords = complex (Clic here for more details about this article) |
8/114. mixed connective tissue disease with multiple organ damage: successful treatment with plasmapheresis.A 24-year-old-woman with mixed connective tissue disease (MCTD) developed multiple organ failure, disseminated intravascular coagulation (DIC), metabolic acidosis, and respiratory and renal failure resulting from visceral vasospasm, so-called visceral Raynaud's phenomenon. After plasmapheresis, the condition of multiple organ failure was markedly improved. The successful treatment with plasmapheresis was dependent upon the removal of immune complexes in serum and improvement of visceral circulation. Thus plasma exchange is recommended as a possible a treatment for multiple organ damage in MCTD.- - - - - - - - - - ranking = 1keywords = complex (Clic here for more details about this article) |
9/114. Autoimmune thyroid dysfunction induced by interferon-alpha treatment for chronic hepatitis c: screening and monitoring recommendations.OBJECTIVE: To analyze the proposed mechanisms of action of recombinant interferon-alpha (IFN-a) in causing autoimmune thyroid dysfunction, to identify pretreatment risk factors, and to provide recommendations for screening and monitoring of thyroid dysfunction during IFN-a therapy for chronic hepatitis c. methods: Selected publications were reviewed to analyze the proposed mechanisms of autoimmune thyroid disorders. In addition, we examined the interrelationship of the thyroid and the liver, the occurrence of thyroid dysfunction in patients with chronic hepatitis c before and after IFN-a therapy, and the presence or absence of antithyroid antibodies in association with thyroid disease. case reports were selected to demonstrate various IFN-a-induced thyroid dysfunction. RESULTS: IFN-a induces thyroid dysfunction in 3 to 14% of all treated patients with chronic hepatitis c, leading to hypothyroidism, hyperthyroidism, or thyroiditis. In a few patients, thyroid disease will develop in the absence of antithyroid antibodies, a scenario that suggests a nonimmune-mediated mechanism. More frequently, patients develop antithyroid antibodies, which may progress to overt thyroid dysfunction. Through its immunomodulatory properties, IFN-a seems to act through major histocompatibility complex class I antigens to produce antithyroid antibodies and thyroid disease. CONCLUSION: In patients receiving IFN-a therapy for chronic hepatitis c infection, identifiable risk factors for developing autoimmune thyroid dysfunction are preexisting overt thyroid or autoimmune disease, subclinical thyroid or autoimmune thyroid disease, and female gender. Pretreatment screening is recommended for all patients in whom IFN-a therapy is being considered, and periodic monitoring should be performed during such therapy. Thyroid disease need not be a contraindication to IFN-a therapy; early detection of subclinical or overt thyroid disease may allow uninterrupted continuation of IFN-a treatment.- - - - - - - - - - ranking = 1keywords = complex (Clic here for more details about this article) |
10/114. Autoimmune keratolysis in a patient with leukocytoclastic vasculitis: unusual erythema elevatum diutinum with granulomatous pattern.PURPOSE: Leukocytoclastic vasculitis (LCCV) is an immune complex-mediated, small vessel disease that is clinically characterized by the presence of palpable purpuric lesions, most often in association with rheumatic diseases. Ocular manifestations of LCCV are rare. methods: We describe a patient with an unusual granulomatous pattern of erythema elevatum diutinum (EED) associated with autoimmune keratolysis. RESULTS: We studied a 64-year-old man with decreased visual acuity and nodular lesions in both hands. Ocular examination revealed bilateral superior corneal melting with perforation in the left eye and conjunctival thickening in both eyes, in association with a severe inflammatory reaction. Histopathologic examination of the conjunctiva revealed granulomatous vasculitis with neutrophilic infiltrate, giant cells, and fibroblastic proliferation. A punch biopsy taken from his skin showed similar characteristics that suggested EED; however, there were no giant cells. CONCLUSION: To our knowledge, autoimmune keratolysis secondary to cutaneous LCCV (EED) has not been described previously, and there has been no description of granulomatous reaction (in the conjunctiva) in EED.- - - - - - - - - - ranking = 1keywords = complex (Clic here for more details about this article) |
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