Immunoglobulin autoimmunity

Issues regarding the influence of duration or intensity of exposure in relation to effect on autoimmune disease processes are questions that have not been established, with some inconsistencies seen in the epidemiologic studies (Table 25.2). Dose or intensity of silica exposure affects the clearance from the lung and silica-containing macrophages can be translocated to pulmonary lymph nodes. Increased production of immunoglobulins and of lymphocyte-derived interferon-gamma is seen at these sites.49... 

The immunological disorders of Indian childhood cirrhosis and of tropical splenomegaly syndrome, where there are disturbances of the immunoglobulin synthesis as well as defects of cellular immune responses, may be the results of a combination of infections and perhaps certain types of unusual autoimmune phenomena—or even to vitamin deficiencies. 

Immunoglobulin obtained from pooled plasma obtained from hepatitis B and HIV negative donors is used as an aspecific immunostimulant in immunodeficiency diseases, idiopathic thrombocytopenia, autoimmune hemolytic anemias, Kawasaki syndrome and to prevent infections in immune compromised patients with leukemia or multiple myeloma. Adverse effects include potentially severe hypersensitivity reactions. 

Bayry J, Thirion M, Misra N, Thorenoor N, Delignat S, Lacroix-Desmazes S et al. Mechanisms of action of intravenous immunoglobulin in autoimmune and inflammatory diseases. Neurol Sci 2003 24 S217-21. 

Dapsone is approved for the treatment of an autoimmune blistering skin disease, dermatitis herpetiformis. This intensely pruritic eruption is characterized histologically by a dense dermal infiltration of neutrophils and subepidermal blisters. Other skin diseases in which dapsone is helpful are linear immunoglobulin A (IgA) dermatosis, subcorneal pustular dermatosis, leukocytoclastic vasculitis, and a variety of rarer eruptions in which neutrophils predominate, including some forms of cutaneous lupus erythematosus. 

Stangel M, Hartung HP, Marx P, Gold R. Intravenous immunoglobulin treatment of neurological autoimmune diseases. J Neurol Sci 1998 153(2) 203-14. 

Bayary J, Dasgupta S, Misra N, et al. Intravenous immunoglobulin in autoimmune disorders an insight... 

Direct evidence that apoptotic cells can induce autoimmunity comes from experiments in which normal mice injected with syngeneic apoptotic thymocytes developed antinuclear, anticardiolipin, and anti-ssDNA antibodies. These mice suffered from immunoglobulin G deposition in the glomeruli several months after immunization (M16). How do apoptotic cells induce production of autoantibodies ... 

Membrane plasmapheresis is also the first step for treatment of pathological plasma in the case of autoimmune diseases, as the patient retains his own red blood cells while his plasma is replaced by an albumin solution or fresh frozen plasma obtained from donors (plasma exchange therapy). Other more selective plasma purification techniques consist in eliminating pathologic immunoglobulins or LDL cholesterol familial hypercholesterolemia, either by a secondary filtration, chemical adsorption or immunoadsorption. A description of various applications of plasmapheresis can be found in the book edited by Smit Sibinga and Rater [15]. 

The evidence of an autoimmune pathogenesis supports the use of immunomodulatory therapy in PNS. If therapy is started at an early stage of the disease, the chances of neurological improvement are better, both with intravenous immunoglobuline alone [225] and with plasmapheresis and chemotherapy in combination even if no tumor has been diagnosed [226]. 

Hadden RD, Gregson NA, Gold R, Smith KJ, Hughes RA. Accumulation of immunoglobulin across the blood-nerve barrier in spinal roots in adoptive transfer experimental autoimmune neuritis. Neuropathol Appl Neurobiol 2002 28(6) 489-97. 

In addition to cancer, too little apoptosis can also result in diseases such as autoimmune lymphoproliferative syndrome (ALPS). This occurs when there is insufficient apoptosis of auto-aggressive T cells, resulting in multiple autoimmune diseases. An overproliferation of B cells occurs as well, resulting in excess immunoglobulin production, leading to autoimmunity. Some of the common diseases of ALPS include hemolytic anemia, immune-mediated thrombocytopenia, and autoimmune neutropenia. The different types of this condition are caused by different mutations. Type 1A results from a mutation in the death domain of the Fas receptor, Type IB results from a mutation in Fas ligand, and Type 2 results from a mutation in caspase 10, reducing its activity. 

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