No abstract

Pemphigus vulgaris is a cutaneous autoimmune disease in which the occurrence of autoantibodies directed against desmoglein-3 and other self-antigens has been well established in patient sera. However, V-region interactions (connectivity) of serum IgG and IgM have not been analysed to date. In this report, it has been demonstrated that IgG and IgM in the sera of pemphigus vulgaris patients bind a preparation of F(ab')2 fragments fractionated according to their isoelectric points, and that a pattern of connectivity distinguishable from that of healthy donor sera arises when the sera are tested against 20 individual isoelectric-focusing-separated F(ab')2-containing fractions. This suggests that there are alterations in regulatory networks. In spite of the fact that prednisolone-based treatment of pemphigus patients has proved to be effective in controlling the disease, some undesirable effects associated with this form of treatment have prompted investigation into other therapeutic approaches. One possible approach to the treatment of this autoimmune disease is the use of high doses of normal polyclonal immunoglobulins. In fact there are a few reports of the empirical intravenous administration of immunoglobulins to pemphigus vulgaris patients. The results presented here provide the rational basis for using such a treatment, since it is demonstrated that a deviation from healthy V-region interactions can be attributed to pemphigus patients and that such a condition is considered to be modified by this type of immunotherapy.

The ACE D/D genotype was associated with nitric oxide metabolite levels and systolic blood pressure in clinically healthy men while it had no effect in women.

Following primary infection with human immunodeficiency virus (HIV)-1, antibodies against specific HIV-1 epitopes are elicited. However, non-HIV-1 specific antibodies, including autoantibodies, also arise. In fact, it has been proposed that such autoantibodies have an important role in the pathogenesis of HIV-1 infection. Because an imbalance in connectivity has been associated with autoimmune processes, we investigated the connectivity status of HIV-1-infected individuals. Moreover, we tested the possible role of viral load and CD4(+) T-cell counts, in connectivity, because these parameters appear to be important in the prognosis of HIV-1 infection. Results show that indeed, there is an alteration in connectivity in these patients, both for immunoglobulin (Ig)G and IgM, which is an immune alteration not previously identified in HIV-1 infection. In addition, our results show that viral load and CD4(+) T-cell counts are both equally important in defining the characteristic pattern of connectivity in HIV-1-infected individuals, and that neither is independently responsible for alterations in patient connectivity status.

The effects of acid-functionalized and polycitric acid- (PCA-) polymerized carbon nanotubes (CNTs) in contact with the extracellular membrane of mesenchymal stem cells (MSC), a genetically unmodified cell line with differentiation capability, was evaluated with different cellular parameters. The modified CNTs show differences in the analyzed biological behaviors, that is, intracellular incorporation, cell proliferation, apoptosis, and cytotoxicity as compared with those unpolymerized nanotubes. Due to the reduced cellular uptake of polymerized CNTs, PCA-polymerized CNTs are less cytotoxic and are associated with less apoptotic cell death than the acid-functionalized ones. The effects of nitrogen-doped CNTs (CNx) is also reported, showing that functionalized undoped CNTs present strong stimulation of cell proliferation, whereas functionalized and polymerized CNxs stimulate an apoptotic behavior. The study of MSCs in contact with CNTs and PCA is challenging due to the complexity of its various signaling components. Our results provide basis for further studies aimed to understand the relevant role that the interaction of these nanotubes with extracellular membrane could have a crucial structure for tissue grafting.