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
L. Weiss, A.M. Botero-Anug, C. Hand, S. Slavin and D. Naor
Background: Standard CD44 and its alternatively spliced variants were found to be associated with the metastatic potential of tumor cells and with cell migration of autoimmune inflammatory cells, including cells involved in experimental insulin-dependent diabetes mellitus.
Objectives: To investigate whether induction of anti-CD44 immune reactivity, through cDNA vaccination, could attenuate IDDM in a transfer model of NOD mice.
Methods: Our vaccination technique involved the insertion of CD44s or CD44v cDNA into a silicone tube filled with a 2.5 cm long segment of hydroxylated-polyvinyl acetate wound dressing sponge (forming a virtual lymph node) which was implanted under the skin of male NOD recipients reconstituted with diabetogenic spleen cells of female NOD donors. The VLN were implanted 20 days before and 3 days after cell transfer.
Results: In contrast to control groups of recipient mice, recipients vaccinated with VLN loaded with CD44v or CD44s cDNAs developed resistance to IDDM almost to the same extent. Our results suggest that the gene vaccination effect was mediated by anti-CD44 antibody rather than by cellular immunity. Histopathological examinations revealed a significant protection of pancreatic islets in the DNA-vaccinated recipients, whereas the islets of control recipients of diabetogenic cells were almost totally destroyed.
Conclusions: These findings may open new opportunities for IDDM therapy in the future.
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.
M. Abu-Shakra, S. Codish, L. Zeller, T. Wolak and S. Sukenik
Atherosclerotic disease is common in systemic lupus erythematosus and is the result of multiple pathogenic mechanisms that include traditional risk factors as well as SLE-related factors. Endothelial dysfunction and arterial stiffness contribute significantly to the atherogenic process. Dobutamine stress echocardiogram has not been shown to detect subclinical coronary artery disease; however the high percentage of left ventricular outflow gradient requires further evaluation and follows-up studies.
M. Szyper-Kravitz, A. Altman, J.F. de Carvalho, F. Bellisai, M. Galeazzi, Y. Eshet and Y. Shoenfeld
The antiphospholipid syndrome is characterized by recurrent fetal loss, venous and/or arterial thrombosis, and thrombocytopenia associated with elevated titers of lupus anticoagulant and anticardiolipin antibodies. Although thrombosis is the characteristic vascular involvement in APS, the development of vascular aneurysms in patients with APS has been reported. We describe four patients with established APS, who developed abdominal aortic aneurysm, and review the literature on previous published cases of arterial aneurysms developing in patients with APS. In addition, we discuss the possible pathophysiological association between APS and the development of this vascular abnormality.
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.
Y. Sherer, S. Kuechler, J. Jose Scali, J. Rovensky, Y. Levy, G. Zandman-Goddard and Y. Shoenfeld
Background: Systemic lupus erythematosus is an autoimmune disease with diverse clinical manifestations that cannot always be regulated by steroids and immunosuppressive therapy. Intravenous immunoglobulin is an optional immunomodulatory agent for the treatment of SLE, but the appropriate indications for its use, duration of therapy and recommended dosage are yet to be established. In SLE patients, most publications report the utilization of a high dose (2 g/kg body weight) protocol.
Objectives: To investigate whether lower doses of IVIg are beneficial for SLE patients.
Methods: We retrospectively analyzed the medical records of 62 patients who received low dose IVIg (approximately 0.5 g/kg body weight).
Results: The treatment was associated with clinical improvement in many specific disease manifestations, along with a continuous decrease in SLEDAI scores (SLE Disease Activity Index). However, thrombocytopenia, alopecia and vasculitis did not improve following IVIg therapy.
Conclusions: Low dose IVIg is a possible therapeutic option in SLE and is associated with lower cost than the high dose regimen and possibly fewer adverse effects.