M. Blank and Y. Shoenfeld
Idiotypic analyses of anti-DNA autoantibodies were widely reported a decade ago. More than 100 studies were conducted on one of the main analyzed idiotypes, the 16/6 Id of the anti-ssDNA monoclonal antibody. In this review we summarize current knowledge on the characteristics of the 16/6 Id, its link to infection and its target epitopes on other molecules known so far. This includes the modulation of T and B cell responses and gene expression by the 16/6 mAb in vitro and in vivo. We focus on the ability and mechanisms by which this idiotype induces experimental lupus in naïve mice, manifested by autoantibody spread, kidney and brain involvement, and leukopenia associated with enhanced sedimentation rate. We also discuss various therapeutic modalities to treat 16/6 induced lupus in mice.
E. Mozes, U. Sela and A. Sharabi
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.
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.
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.
G. Markel, M. Imazio, A. Brucato and Y. Adler
The most troublesome complication of acute pericarditis is recurrent episodes of pericardial inflammation, which occur in 15–32% of cases. It was recently found that viral infection has a major role, but in many cases the cause is unknown. The optimal method for prevention has not been fully established; accepted modalities include non-steroidal anti-inflammatory drugs, corticosteroids, immunosuppressive agents, and pericardiectomy. Based on the proven efficacy of colchicine in familial Mediterranean fever, several small and large-scale international clinical trials have shown the beneficial effect of colchicine therapy in preventing recurrent pericarditis. Indeed, colchicines-treated patients consistently display significantly fewer recurrences, longer symptom-free periods, and even when attacks occur they are weaker and shorter in nature. It was also found that pretreatment with corticosteroids substantially attenuates the efficacy of colchicine, as evidenced by significantly more recurrences and longer therapy periods. Colchicine is a safe and effective modality for the treatment and prevention of recurrent pericarditis, especially as an adjunct to other modalities, since it provides a sustained benefit superior to all current modalities. The safety profile seems superior to other drugs such as corticosteroids and immunosuppressive drugs.
E. Toubi
Among the several mechanisms that play a role in maintaining peripheral self-tolerance is the existence of a unique CD4+CD25+ population of naturally occurring regulatory T cells, which actively prevent both the activation and the effector function of autoreactive T cells that have escaped different mechanisms of tolerance. Many studies have shown the benefit of targeting this cell population by restoring self-tolerance. Therapies that could possibly increase the suppressive ability of T regulatory cells were proven to improve the course of autoimmune diseases.
D. Buskila and P. Sarzi-Puttini
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.