Geo-epidemiology and autoimmunity

Autoimmune disease (AD) affects approximately 3% of the population. This is an enormous number, but ironically the study of autoimmunity has not taken on the significance of many other diseases because so many of the ADs are relatively uncommon. Indeed, despite enormous advances in the diagnosis and the treatment of AD, there is still a paucity of data on the etiological events that lead to the clinical pathology. For most other human diseases, the etiology is addressed and often solved by the use of epidemiology. Epidemiology consists of the study of prevalence of a disease, coupled with analysis of genetic factors and detection of environmental agents. In the context of autoimmune conditions, preclinical epidemiology has recently been favored, as a consequence of the discovery that autoantibody precedes overt disease. The idea of a North–South gradient in the prevalence of ADs, with a reciprocal gradient in that of infectious injuries has proven to be debatable. More importantly, environmentally-induced changes have been shown to modify certain diseases giving rise to the key concept of epigenetics. However, it is clear that major voids exist. Some of these voids were hoped to be solved by the use of genome-wide associations. This, however, has proven very problematic, as the genetic basis of AD is considerably more complicated than once believed. We now base our hopes on next generational sequencing as a brut force undertaking to partially decipher the genetic code that predisposes individuals to AD. This volume is a compilation of papers in Autoimmunity Reviews and the Journal of Autoimmunity and presented as part of the 7th International Congress on Autoimmunity in Ljubljana, Slovenia. It is clearly impossible to present data on the geoepidemiology of all of the AD. Instead, we attempted to generate interest amongst immunologists to generate papers that are thought provoking but also contemporary reviews.     

Epigenetics and autoimmunity

Advances in genetics, such as sequencing of the human genome, have contributed to identification of susceptible genetic patterns in autoimmune diseases (AID). However, genetics is only one aspect of the diseases that does not reflect the influence of environment, sex or aging. Epigenetics, the control of gene packaging and expression independent of alterations in the DNA sequence, is providing new directions linking genetics and environmental factors. Recent findings have contributed to our understanding of how epigenetic modifications could influence AID development, showing differences between AID patients and healthy controls but also showing how one disease differs from another. With regards to epigenetic abnormalities, DNA methylation and histone modifications could be affected leading to large spatial and temporal changes in gene regulation. Other epigenetic processes, such as the influence of the ionic milieu around chromatin and DNA supercoiling stresses may be suspected also. The newly described role of microRNAs in control of gene expression is important by promoting or suppressing autoreactivity in AID. As a consequence control of cellular processes is affected becoming conducive, for example, to the development of autoreactive lymphocytes in systemic lupus erythematosus, synoviocyte proliferation in rheumatoid arthritis, or neural demyelination in multiple sclerosis. Application of epigenetics to AID is in its infancy and requires new hypotheses, techniques, tools, and collaborations between basic epigenetic researchers and autoimmune researchers in order to improve our comprehension of AID. From this will arise new therapeutics, means for early intervention, and perhaps prevention.     

Role of B-cell antigen receptor-associated molecules and lipid rafts in CD5-induced apoptosis of B CLL cells.

A total of 40 patients with B-CLL were investigated for CD5-triggered apoptosis and categorized as 20 resistant (group I) and 20 sensitive patients (group II). The densities of surface IgM (sIgM) and CD5 were lower in group I than group II, as were the percentages of CD79b+, CD38+, and Zap70-expressing B cells. CD5 signaling was mediated through the BCR in group II B cells, as established by coimmunoprecipitation of CD5 and CD79a and tyrosine phosphorylation of CD79a. Following colocalization of CD5 and sIgM in membrane lipid rafts (LRs), Syk became associated with these molecules, whereas SHP-1 was uncoupled from CD5. Nonresponsiveness to CD5 cross-linking in group I was ascribed to three possible abnormalities, and defined as three subgroups of patients. In subgroups Ia and Ib, CD5 and sIgM colocalized within the LRs. SHP-1 remained attached to the BCR in subgroup Ia, but not in subgroup Ib, where signal transduction was associated with an excess of truncated CD79b. In subgroup Ic, CD5 and sIgM segregated into different LRs, resulting in no signaling of apoptosis.     

Stem and Progenitor Cell Expansionin Co-culture of Mobilized CD34~ Cells and Osteopetrotic Mouse Stroma

1 IntroductionCulture systems capable of expanding and/or maintaining hematopoietic stem cells will not only facilitate our understanding of stem cell biology, but also broaden clinical applications. Among various in vitro hematopoietic culture systems, co-cultures of marrow or CD34~ cells with an adherent stromal layer that can produce cytokines and extracellular matrix components most effectively supports long-term hematopoiesis (LTC), mimicking the bone marrow micro-environment.The OP-9 stromal cells ar...     

Effect of Whitening Agents on Dentin Bonding

Background: Several studies have shown a reduction in enamel bond strengths when the bonding procedure is carried out immediately after vital bleaching with peroxides. This reduction in bond strengths has become a concern in cosmetic dentistry with the introduction of new “in‐office” and “waiting‐room” bleaching techniques. The aim of this in vitro study was to evaluate the effect of three bleaching regimens: 35% hydrogen peroxide (HP), 35% carbamide peroxide (CP), and 10% CP, on dentin bond strengths. Materials and Methods: One hundred and twenty fresh bovine incisors were used in this study. The labial surface of each tooth was ground flat to expose dentin and was subsequently polished with 600‐grit wet silicon carbide paper. The remaining dentin thickness was monitored and kept at an average of 2 mm. The teeth were randomly assigned to four bleaching regimens (n = 30): (A) control, no bleaching treatment; (B) 35% HP for 30 minutes; (C) 35% CP for 30 minutes; and (D) 10% CP for 6 hours. For each group, half of the specimens (n = 15) were bonded with Single Bond/Z100 immediately after the bleaching treatment, whereas the other half was bonded after the specimens were stored for 1 week in artificial saliva at 37°C. The specimens were fractured in shear using an Instron machine. Results: For the groups bonded immediately after bleaching, one‐way analysis of variance (ANOVA) followed by the Duncan's post hoc test revealed a statistically significant reduction in bond strengths in a range from 71% to 76%. For the groups bonded at 1 week, one‐way ANOVA showed that group B (35% HP for 30 min) resulted in the highest bond strengths, whereas 10% CP resulted in the lowest bond strengths. Student's t‐test showed that delayed bonding resulted in a significant increase in bond strengths for groups B (35% HP) and C (35% CP); whereas the group bleached with 10% CP (group D) remained in the same range obtained for immediate bonding. Storage in artificial saliva also affected the control group, reducing its bond strengths to 53% of the original.