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
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.
A. Kapitany, Z. Szabo, G. Lakos, N. Aleksza, A. Vegvari. L. Soos, Z. Karanyi, S. Sipka, G. Szgedi and Z. Szekanecz
Background: The presence of anti-cyclic citrullinated peptide autoantibody is highly specific for rheumatoid arthritis. Certain HLA-DR4 (HLA-DRB1*04) alleles, also known as the "shared epitope," are associated with increased susceptibility to RA. In addition, these alleles may also have relevance for disease outcome. Anti-CCP antibody positivity has been associated with the presence of HLA-DR4 alleles in patients with RA. However, there is little information available regarding any relationship between quantitative anti-CCP production (serum anti-CCP concentrations) and the shared epitope.
Objectives: To determine the association between anti-CCP antibody production and various HLA-DRB1 alleles.
Methods: Serum anti-CCP, rheumatoid factor and C-reactive protein levels were assessed in 53 RA patients. All these patients underwent HLA-DRB1 genotyping.
Results: Of the 53 patients 33 (62%) were positive for anti-CCP antibody. We found significant correlations between anti-CCP and RF positivity (chi-square = 6.717, P < 0.01), as well as between anti-CCP and HLA-DRB1*04 positivity (chi-square = 5.828, P < 0.01). There was no correlation between RF positivity and serum levels, CRP serum levels and HLA-DRB1*04 positivity. When quantitatively comparing serum anti-CCP levels with shared epitope positivity, patients carrying one or two copies of HLA-DRB1*04 alleles had significantly higher anti-CCP concentrations (530.0 ± 182.6 U/ml) compared to DRB1*04-negative patients (56.8 ± 27.4 U/ml) (P < 0.01). There was no difference in serum anti-CCP antibody concentrations between patients carrying only one HLA-DRB1*01 allele but no HLA-DRB1*04 allele (12.0 ± 8.6 U/ml) in comparison to SE-negative patients (76.8 ± 56.2 U/ml). Regarding non-SE HLA-DRB1 genotypes, all 6 patients (100%) carrying DRB1*15 alleles and 6 of 7 (85%) patients carrying DRB1*13 were anti-CCP positive. In addition, patients with HLA-DRB1*13 (282.5 ± 23.8 U/ml) and DRB1*15 (398.7 ± 76.2 U/ml) produced significantly more anti-CCP than did any other non-SE HLA-DRB1 subtypes (P < 0.01).
Conclusions: There is significant association between anti-CCP and RF, as well as between anti-CCP and SE positivity in RA. In addition, the presence of one or two copies of HLA-DRB1*04 alleles has been associated with higher serum anti-CCP antibody levels. Thus, patients carrying HLA-DRB1*04 alleles exhibited an overall tenfold increase in serum anti-CCP antibody levels in comparison to HLA-DRB1*04-negative subjects. Increased anti-CCP production may also be associated with other non-SE HLA-DRB1 genotypes, such as DRB1*13 or DRB1*15. In reports by other investigators, both anti-CCP concentrations
E. Mozes, U. Sela and A. Sharabi
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. 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
Y. Katz, M.R. Goldberg, G. Zadik-Mnuhin, M. Leshno and E. Heyman
Background: Immunoglobulin E-mediated allergy to cow’s milk protein represents a major problem for infants who are not breast fed. A search for substitute milks revealed a cross-allergenicity to milk derived from goat and sheep but not to milk from a mare. We noted that the cow, goat and sheep species are both artiodactyls and ruminants, defining them as kosher animals, in contrast to the mare.
Objectives: To determine whether patients with IgE-mediated cow’s milk allergy are cross-sensitized to milk from other species such as the deer, ibex, buffalo, pig and camel.
Methods: Patients with a clinical history consistent with IgE-mediated cow's milk protein allergy were tested by skin prick test to validate the diagnosis. They were then evaluated by skin-prick test for cross-sensitization to milk-derived proteins from other species.
Results: All patients allergic to cow's milk tested positive by skin-prick test for cross-reactivity to deer, Ibex and buffalo (n=24, P = 0). In contrast, only 5 of the 24 patients (20.83%) tested positive to pig milk and only 2 of 8 (25%) to camel’s milk. Cross-sensitization to soy milk was noted in 4 of 23 patients (17.39%), although they all tolerated oral ingestion of soy-containing foods.
Conclusions: A significant cross-sensitization to milk proteins derived from kosher animals exists in patients allergic to cow's milk protein, but far less so compared to the milk proteins from non-kosher animals tested. Patients with proven IgE-mediated allergy to cow’s milk can utilize the above findings to predict suitable alternative sources of milk.