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When evaluating a patient with suspected primary amyloidosis, it is important to consider other causes of the presenting symptoms and signs, including multiple myeloma, hemochromatosis, sarcoidosis, Waldenstr m s macroglobulinemia, metastatic tumors, and other cause of nephrotic syndrome, such as lupus nephritis
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produced and may have physiologic roles in cellular interactions Positive serologic findings may be found years before the development of pathogenic autoimmunity or clinical illness, and in some cases, they represent normal immunity or benign autoimmunity without disease The major theories regarding the development of autoimmune disease are (1) release of normally sequestered antigens; (2) escape from anergy or defective apoptosis (programmed cell death) leading to abnormal autoreactive cellular clones; (3) shared antigens between the host and microorganisms, ie, molecular mimicry ; and (4) defects in helper or suppressor T cell function A genetic susceptibility is also a likely determinant of autoimmune disease In nearly all autoimmune diseases, multiple mechanisms of autoimmunity are operative
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1 Cell-Mediated Autoimmunity
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Certain autoimmune diseases are mediated by T cells that have become specifically immunized to autologous tissues Cytotoxic or killer T cells generated by this aberrant immune response injure specific organs in the absence of serum autoantibodies Diminished suppressor T cell activity or loss of clonal anergy results in disordered regulation of immune function and consequent autoreactivity The immune damage in systemic (non-organ-specific) diseases such as systemic lupus erythematosus may be due to such a mechanism
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Treatment of localized amyloid tumors is by surgical excision There is no effective treatment of systemic amyloidosis, and death usually occurs within 1 3 years Care is generally supportive, although hemodialysis and immunosuppressive therapy may be useful When concomitant multiple myeloma is found, it is treated in the standard way (see 13) Secondary disease is usually approached by aggressively treating the predisposing disease, but remission of fibril deposition does not occur Bone marrow transplant after chemotherapy has been used in selected patients
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2 Antibody-Mediated Autoimmunity
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Several autoimmune diseases have been shown to be caused by autoantibodies in the absence of cell-mediated autoimmunity The autoimmune hemolytic anemias, idiopathic thrombocytopenia, and Goodpasture s syndrome appear to be mediated solely by autoantibodies directed against autologous cell membrane constituents In these diseases, antibody attaches to cell membranes and fixes complement; the ensuing inflammatory reaction injures the cells Anti-receptor antibodies that compete with or mimic physiologic agonists for cellular receptors cause several diseases In Graves disease, antibodies are present that bind to thyroid cells thyroid-stimulating hormone receptors and thereby stimulate thyroid hormone production In rare instances of type 1 diabetes mellitus, anti-insulin receptor antibodies cause insulin resistance in peripheral target tissues Antibodies to acetylcholine receptors of the myoneural junction in myasthenia gravis block neuromuscular transmission and produce muscle weakness
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5 Heavy Chain Disease ( , , )
These are rare disorders in which the abnormal serum and urine protein is a part of a homogeneous , , or heavy chain The clinical presentation is more typical of lymphoma than multiple myeloma, and there are no destructive bone lesions Chain disease presents as a lymphoproliferative disorder with autoimmune features Chain disease is frequently associated with severe diarrhea and infiltration of the lamina propria of the small intestine with abnormal plasma cells Chain disease is associated with chronic lymphocytic leukemia
Gertz MA et al Amyloidosis: diagnosis and management Clin Lymphoma Myeloma 2005 Nov;6(3):208 19 [PMID: 16354326] Gertz MA et al Amyloidosis Best Pract Res Clin Haematol 2005;18(4):709 27 [PMID: 16026746] Merlini G et al Molecular mechanisms of amyloidosis N Engl J Med 2003 Aug 7;349(6):583 96 [PMID: 12904524] Vesole DH et al; Plasma Cell Disorders Working Committee of the Center for International Blood and Marrow Transplant Research High-dose therapy and autologous hematopoietic stem cell transplantation for patients with primary systemic amyloidosis: a Center for International Blood and Marrow Transplant Research Study Mayo Clin Proc 2006 Jul;81(7): 880 8 [PMID: 16835967]
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