Y. Shoenfeld, B. Gilburd, M. Abu-Shakra, H. Amital, O. Barzilai, Y. Berkun, M. Blank, G. Zandman-Goddard, U. Katz, I. Krause, P. Langevitz, Y. Levy, H. Orbach, V. Pordeus, M. Ram, Y. Sherer, E. Toubi and Y. Tomer
Y. Shoenfeld, G. Zandman-Goddard, L. Stojanovich, M. Cutolo, H. Amital, Y. Levy, M. Abu-Shakra, O. Barzilai, Y. Berkun, M. Blank, J.F. de Carvalho, A. Doria, B. Gilburd, U. Katz, I. Krause, P. Langevitz, H. Orbach, V. Pordeus, M. Ram, E. Toubi and Y. Sherer
Y. Shoenfeld, M. Blank, M. Abu-Shakra, H. Amital, O. Barzilai, Y. Berkun, N. Bizzaro, B. Gilburd, G. Zandman-Goddard, U. Katz, I. Krause, P. Langevitz, I.R. Mackay, H. Orbach, M. Ram, Y. Sherer, E. Toubi and M.E. Gershwin
R.E. Voll, V. Urbonaviciute, M. Herrmann and J.R. Kalden
High mobility group box 1 is a nuclear protein participating in chromatin architecture and transcriptional regulation. When released from cells, HMGB1 can also act as a pro-inflammatory mediator or alarmin. Upon stimulation with lipopolysaccharides or tumor necrosis factor-alpha, HMGB1 is secreted from certain cells such as monocytes/macrophages and fosters inflammatory responses. In addition, HMGB1 is passively released from necrotic cells and mediates inflammation and immune activation. In contrast, during apoptotic cell death, nuclear HMGB1 gets tightly attached to hypo-acetylated chromatin and is not released into the extracellular milieu, thereby preventing an inflammatory response. There is accumulating evidence that extracellular HMGB1 contributes to the pathogenesis of many inflammatory diseases, including autoimmune diseases. Increased concentrations of HMGB1 have been detected in the synovial fluid of patients with rheumatoid arthritis. In animal models of RA, HMGB1 appears to be crucially involved in the pathogenesis of arthritis, since neutralization of HMGB1 significantly ameliorates the disease. Also, in the serum and plasma of patients with systemic lupus erythematosus we detected substantial amounts of HMGB1, which may contribute to the disease process. However, investigations of blood concentrations of HMGB1 and its relevance in human diseases are hindered by the lack of reliable routine test systems.
E. Zifman and H. Amitai
Medical screening is not a tangible existent tool in autoimmune disorders as it is in other illnesses. Numerous attempts are made to identify individuals destined to develop an autoimmune disease, including analysis of the genetic background, which along with the immunological profile, may assist in identifying those individuals. If these efforts turn out to be successful they may lead to the possibility of proactive measures that might prevent the emergence of such disorders. This review will summarize the attempts made to pursue autoantibodies specific for the central nervous system as potential predictors of autoimmune neurological disorders.
S. Bar-Sela and Y. Shoenfeld
Two patients working for several years in the operation and maintenance of photocopy machines developed an autoimmune disease. In both, early manifestations were thromboembolic phenomena associated with anticardiolipin antibodies. Joint and kidney involvement emerged later, with the appearance of other autoantibodies. These two patients were occupationally exposed to ultraviolet irradiation, ozone emission, and possibly some oxides of heavy metals. To our knowledge this is the first report of occupational autoimmune disease in photocopy machine workers, and the first description of antiphospholipid syndrome as an occupational disease. The possible cause-effect inter-relationship between their occupational exposure and autoimmune disease is discussed.
D. Buskila and P. Sarzi-Puttini
G. Zandman-Goddard and Y. Shoenfeld
Controlling iron/oxygen chemistry in biology depends on multiple genes, regulatory messenger RNA structures, signaling pathways and protein catalysts. Ferritin synthesis is regulated by cytokines (tumor necrosis factor-alpha and interleukin-1α) at various levels (transcriptional, post-transcriptional, translational) during development, cellular differentiation, proliferation and inflammation. The cellular response by cytokines to infection stimulates the expression of ferritin genes. The immunological actions of ferritin include binding to T lymphocytes, suppression of the delayed-type hypersensitivity, suppression of antibody production by B lymphocytes, and decreased phagocytosis of granulocytes. Thyroid hormone, insulin and insulin growth factor-1 are involved in the regulation of ferritin at the mRNA level. Ferritin and iron homeostasis are implicated in the pathogenesis of many disorders, including diseases involved in iron acquisition, transport and storage (primary hemochromatosis) as well as in atherosclerosis, Parkinson's disease, Alzheimer disease, and restless leg syndrome. Mutations in the ferritin gene cause the hereditary hyperferritinemia-cataract syndrome and neuroferritinopathy. Hyperferritinemia is associated with inflammation, infections and malignancies, and in systemic lupus erythematosus correlates with disease activity. Some evidence points to the importance of hyperferritinemia in dermatomyositis and multiple sclerosis, but further mechanistic investigations are warranted.