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.
S. Fuchs, T. Feferman, R. Meidler, T. Brenner, O. Laub and M.C. Souroujon
Backgraound: Intravenous immunoglobulin administration has been beneficially used for the treatment of a variety of autoimmune diseases including myasthenia gravis, although its mode of action and active components have not yet been fully identified.
Objectives: To isolate from IVIg a disease-specific fraction involved in the therapeutic activity in myasthenia and to identify its properties and function.
Results: IVIg administration in experimental autoimmune MG results in suppression of disease that is accompanied by decreased Th1 cell and B cell proliferation. Chromatography of IVIg on columns of IgG from rats with EAMG or from MG patients resulted in depletion of the suppressive activity that IVIg has on rat EAMG. Moreover, the minute amounts of IgG fractions eluted from the EAMG or MG-specific columns retained the immunosuppressive activity of IVIg.
Conclusions: Our study supports the notion that the therapeutic effect of IVIg is mediated by a minor disease-specific immunoglobulin fraction that is present in IVIg and is essential for its therapeutic activity.
V. Pordeus, O. Barzilai, Y. Sherer, R.R. Luiz, M. Blank, N. Bizzaro, D. Villalta, J-M. Anaya and Y. Shoenfeld
Background: Infectious agents are important in the pathogenesis of autoimmune disease since they are a major part of the environmental trigger of autoimmunity. A negative relationship between latitude and infectious disease species richness has been suggested.
Objectives: To examine whether their prevalence differs in two latitudinally different populations.
Methods: The prevalence of infections with Toxoplasma gondii, rubella virus, cytomegalovirus, Epstein-Barr virus and Treponema pallidum was compared between subjects from Italy and Colombia.
Results: We found high titers of antibodies against four of five microorganisms tested, Toxoplasma gondii (50.8%), rubella virus (German measles) (75%), cytomegalovirus (86.3%), Epstein-Barr virus (83.3%) and Treponema pallidum (6.3%) in completely healthy individuals from a tropical country (Colombia) and a European country (Italy). Differences between two groups of volunteers were noted regarding two infectious agents. The prevalence of immunoglobulin G anti-rubella antibodies was significantly higher among Italian subjects (85% vs. 67.9%, P = 0.002), whereas antibodies against CMV were less prevalent among Italian as compared to Colombian subjects (77% vs. 92.9%, P < 0.001).
Conclusions: These differences might also result in a different tendency towards development of autoimmune diseases associated with these infectious agents in different populations.
N. Bassi, D. Amital, H. Amital, A. Doria and Y. Shoenfeld
Chronic fatigue syndrome is a heterogeneous disorder with unknown pathogenesis and etiology, characterized by disabling fatigue, difficulty in concentration and memory, and concomitant skeletal and muscular pain. Several mechanisms have been suggested to play a role in CFS, such as excessive oxidative stress following exertion, immune imbalance characterized by decreased natural killer cell and macrophage activity, immunoglobulin G subclass deficiencies (IgG-1, IgG-3) and decreased serum concentrations of complement component. Autoantibodies were also suggested as a possible factor in the pathogenesis of CFS. Recent studies indicate that anti-serotonin, anti-microtubule-associated protein 2 and anti-muscarinic cholinergic receptor 1 may play a role in the pathogenesis of CFS. It has been demonstrated that impairment in vasoactive neuropeptide metabolism may explain the CFS symptoms
L. Guillevin and C. Pagnoux
Treatment of vasculitides has progressed markedly over the past few decades. Recent therapeutic strategies in severe and refractory anti-neutrophil cytoplasmic antibodies-associated vasculitides include immunomodulating methods (e.g., plasma exchanges), products (such as intravenous immunoglobulins) and, more recently, new agents called biotherapies. Some of them (e.g., anti-tumor necrosis factor-alpha and anti-CD20 monoclonal antibodies) have achieved promising results and are now often used to treat severe cases.