Protective role of anti-idiotypic antibodies in autoimmunity – Lessons for type 1 diabetes

Circulating autoantibodies to beta cell antigens are present in the majority of patients with Type 1 diabetes. These autoantibodies can be detected before and at time of clinical diagnosis of disease. Although the role of autoantibodies in the pathogenesis of the disease is debated, their presence indicates a dysregulation of the humoral immune response. Mechanisms regulating autoantibodies in Type 1 diabetes are not well understood. In contrast, in other autoimmune diseases there is acceptance that autoantibodies are regulated not only by antigen but also by other antibodies that bind to the antigen-binding site of these autoantibodies (anti-idiotypic antibodies). The proposed purpose of this network is to maintain an equilibrium between autoantibodies and their anti-idiotypic antibodies, preventing autoimmunity, while allowing a robust response to exogenous antigen. Anti-idiotypic antibodies regulate both autoantibody binding and their levels by a) neutralizing autoantibodies, and b) inhibiting the secretion of autoantibodies. Because it has been proposed that the B lymphocytes that produce autoantibodies function as autoantigen presenting cells, inhibiting their binding to autoantigen by anti-idiotypic antibodies may prevent development of autoimmune disease. This hypothesis is supported by the presence of anti-idiotypic antibodies in healthy individuals and in patients in remission from autoimmune diseases, and by the lack of anti-idiotypic antibodies during active disease. We recently reported the presence of autoantibodies to glutamate decarboxylase in the majority of healthy individuals, where their binding to autoantigen is prevented by anti-idiotypic antibodies. These anti-idiotypic antibodies are absent at clinical diagnosis of Type 1 diabetes, revealing the presence of autoantibodies. Type 1 diabetes (T1D) is an autoimmune disease characterized by the dysfunction and destruction of insulin-producing beta cells by autoreactive T cells. Although much progress has been made towards understanding the respective roles of effector and regulatory T cells in this beta cell destruction, the development of autoantibodies to beta cell proteins is widely considered simply a by-product of the autoimmune destruction of the beta cells, rather than having an active role in the pathogenesis. This view is starting to change based on increasing recognition that autoantibodies can have defined roles in other autoimmune diseases, and the emergence of new data on their role in T1D. This exploration of the role of autoantibodies in autoimmune disease has been spurred, in part, by increasing recognition that development of autoimmune diseases is influenced by regulatory antibodies (anti-idiotypic antibodies) directed against the unique binding site of autoantibodies. This review provides an overview of the development and function of these anti-idiotypic antibodies, and present evidence supporting their role in the development of autoimmune diseases. Finally, we conclude this review with a model of the events that may cause loss of anti-idiotypic antibodies and the implications for the development of T1D.     

A network analysis of two conceptual approaches to the etiology of PTSD

Two prominent conceptual models of posttraumatic stress disorder (PTSD) are the cognitive model, associated with cognitive processing therapy (CPT; Resick & Schnicke, 1992), and the functional contextualist model, underlying acceptance and commitment therapy (ACT; Hayes et al., 1999). Network analysis was used to examine dynamic interactions among cognitive (relating to CPT) and functional contextualistic (relating to ACT) variables and PTSD symptoms in a sample of 722 trauma-exposed adults. Results from the cognitive networks highlighted the importance of maladaptive beliefs about threat in maintaining the co-occurrence of PTSD symptoms and cognitive variables. Additionally, PTSD symptoms were more likely to lead to cognitive variables, rather than the reverse direction. Results from the functional contextualist networks identified numerous associations amongst variables that contribute to the co-occurrence of PTSD symptoms and psychological inflexibility. Findings from this study may help generate causal hypotheses that can be tested further using a longitudinal study design.     

The establishment of an attachment research network in Latin America: Goals,accomplishments, and challenges

In the face of a pressing need for expanded attachment research programs and attachment informed interventions in Latin America, a research network was established: Red Iberoamericana de Apego: RIA (Iberian-American Attachment Network). The purpose of RIA is to promote human development and well being, informed by attachment theory, centering on research, and with implications for public policies, education, and intervention. We report the proceedings of the second meeting of RIA held in Panama City, Panama, in February 2010. As part of this meeting, RIA sponsored the first Latin-American attachment conference. Proceedings of the conference are described, as are future goals of this new organization.     

Frequency-specific Alterations of Large-scale Functional Brain Networks in Patients with Alzheimer's Disease

Background:

Previous studies have indicated that the cognitive deficits in patients with Alzheimer''s disease (AD) may be due to topological deteriorations of the brain network. However, whether the selection of a specific frequency band could impact the topological properties is still not clear. Our hypothesis is that the topological properties of AD patients are also frequency-specific.

Methods:

Resting state functional magnetic resonance imaging data from 10 right-handed moderate AD patients (mean age: 64.3 years; mean mini mental state examination [MMSE]: 18.0) and 10 age and gender-matched healthy controls (mean age: 63.6 years; mean MMSE: 28.2) were enrolled in this study. The global efficiency, the clustering coefficient (CC), the characteristic path length (CpL), and “small-world” property were calculated in a wide range of thresholds and averaged within each group, at three different frequency bands (0.01–0.06 Hz, 0.06–0.11 Hz, and 0.11–0.25 Hz).

Results:

At lower-frequency bands (0.01–0.06 Hz, 0.06–0.11 Hz), the global efficiency, the CC and the “small-world” properties of AD patients decreased compared to controls. While at higher-frequency bands (0.11–0.25 Hz), the CpL was much longer, and the “small-world” property was disrupted in AD, particularly at a higher threshold. The topological properties changed with different frequency bands, suggesting the existence of disrupted global and local functional organization associated with AD.

Conclusions:

This study demonstrates that the topological alterations of large-scale functional brain networks in AD patients are frequency dependent, thus providing fundamental support for optimal frequency selection in future related research.