Abstract: Psoriatic arthritis (PsA) occurs in approximately 30% of psoriasis patients. Understanding the similarities and differences in the etiology of these related diseases may highlight pathways for intervention and allow risk prediction in the future. Both are complex diseases in which environmental susceptibility factors trigger disease in genetically susceptible individuals. In recent years, genome-wide association studies have been highly successful in identifying genetic susceptibility factors for psoriasis. Most of the psoriasis loci tested so far are also associated with PsA. For example, associations of HLA-Cw*06 and the IL12B and IL23R genes are well-established with both conditions. More recently, analysis of psoriasis genome-wide association studies in a PsA subgroup has also implicated IL23A, TNFAIP3, and TNIP1 genetic variants as conferring risk to PsA. One study has suggested that late cornified envelope (LCE) gene polymorphisms are associated with psoriasis but not PsA. However, this finding was not confirmed by a second study. Similarly, association of the 5q31 gene region encompassing the IL13 gene has been reported with PsA but not psoriasis by one group, but this awaits confirmation in other series. Dedicated genome-wide association studies of PsA are underway and are likely to reveal further insights into why some patients with psoriasis develop arthritis whilst the majority do not. ... Read more

Abstract: Type 1 diabetes (T1D) is an autoimmune disease characterized by the disturbance of pancreatic insulin-producing cells, which results in hyperglycemia. The disease is associated with severe complications that impair the quality of life of individuals. The cause of T1D is unknown. Development of the disease is the result of interactions between immunological, genetic, and environmental factors. Viruses are thought to play an important role in the initiation or acceleration of the disease. This is an important issue since it opens the possibility to develop new preventive and therapeutic strategies to fight the disease. The role of enteroviruses in the development of T1D, in particular type B coxsackieviruses, is supported by epidemiological observations. It has been demonstrated that enterovirus infections were significantly more common in recently diagnosed diabetic patients, compared with control subjects. Enteroviral RNA and/or proteins can be detected in blood samples and intestine biopsies of patients with T1D. The hypothesis of a relationship between enteroviruses and the disease has been strengthened by the presence of enteroviral components or infectious particles in the pancreas of patients with T1D. In this review, arguments in favor of a relationship between enterovirus infections and T1D and the mechanisms of the enteroviral pathogenesis of the disease are presented. ... Read more

Abstract: Systemic sclerosis (SSc, scleroderma) is an autoimmune disease clinically characterized by progressive fibrosis in the skin and internal organs. While the pathogenesis of SSc is not completely understood, familial studies and genetic studies suggest that SSc is a complex polygenic disease. In the current review, we will discuss recent studies investigating genetic susceptibility to SSc. Candidate gene studies have identified critical immunoregulatory genes and gene regions including BANK1, FAM167A-BLK, IL23R, IRF5, STAT4, TBX21, and TNFSF4 as susceptibility genes for the development of SSc. More recently a genome-wide association study has been performed and identified CD247 (CD3-zeta) as a novel genetic risk factor for the susceptibility to SSc. Together these genetic association studies have substantially advanced our understanding of SSc pathogenesis and form the foundation for future studies seeking to understand the complexities of SSc. ... Read more

Abstract: Transplantation of cells, tissues, and organs from one individual to another can incite the production of antibodies specific for foreign antigens, especially major histocompatibility antigens, in the graft. Antibodies specific for a graft provide an index of immunity and a potential trigger for injury and rejection. However, the index of immunity can sometimes miss antibody-mediated rejection and besides causing injury the antibodies against a graft can also protect a graft from injury by blocking immune recognition, called enhancement, regulating activation of complement, and inducing changes in the graft that resist damage. Reviewed here are potential limitations in the use of antibodies as an index of immunity and the ways antibodies cause and/or prevent injury. ... Read more

Abstract: CD8⁺ CTL responses are critical for eliminating virus infected cells in acute infection and in controlling virus replication during chronic infection. Despite evidence of potent HIV-1-specific CD8⁺ CTL responses during the earliest stage of acute infection leading to replacement of founder virus sequence(s) and resolution of peak viral load, in the majority of infected individuals, these responses are inadequate to prevent the establishment or control of persistent infection. Protective CD8⁺ CTL responses have yet to be achieved by vaccine approaches for HIV-1 or other viruses causing persistent infections, Mycobacterium tuberculosis, malaria, and cancer. Understanding the limitations of CD8⁺ CTL responses to keep pace with the diversity of rapidly evolving virus in the case of HIV-1 and HCV and to overcome the diverse and complex mechanisms persistent pathogens employ to escape immune recognition should lead to more effective prophylactic and therapeutic approaches for these diseases. Recent technological advances including single genome amplification (SGA) of plasma viral RNA along with direct amplicon sequencing to identify virus quasispecies, bioinformatics, and statistical methods for the systematic identification of HLA-class I associated escape mutations, and mathematical models that better define the kinetics of virus replication and decay, have provided significant insight into mechanisms of viral transmission and sequence evolution, virus-host interactions, and HIV-1 pathogenesis. In this review we attempt to integrate recent findings from studies in HIV-1, persistent virus infections, and cancer that predict effective T cell responses and suggest approaches that could shift the balance of control in favor of the host immune response. Here, we highlight factors considered essential for effective HIV-1 vaccine CD8⁺ T cell responses: vaccine antigens, quality, magnitude and breadth, mucosal targeting, and formation of CD8⁺ T cell mucosal memory. ... Read more

Abstract: Up to one third of candidates for organ or hematopoietic stem cell transplantation in the United States have antibodies to histocompatibility antigens, the most problematic of which are those of the HLA genetic system. The presence of high levels of HLA-specific antibodies reduces access to transplantation as a treatment option for many patients, and, for others with lower levels, increases the risk of rejection and impacts long term graft survival. Other polymorphic antigens, as well as some autologous antigens, have also been implicated in antibody mediated rejection and may act in concert or synergy with HLA-specific antibodies. The degree of risk imposed by antibodies correlates with their level or strength, with low levels evoking less damage and under some circumstances perhaps even offering some protective benefit. Clinical protocols now provide options for overcoming or circumventing humoral sensitization while research on the signaling pathways triggered by antibodies binding to their target antigens may lead to improved options for therapeutic intervention. ... Read more

Abstract: Chronic rejection following organ transplantation continues to be a major problem in the long-term survival of the engraftment. Recent literature points to role of both the humoral and cellular alloimmune responses in the pathogenesis of chronic rejection. Our recent studies have provided evidence for alloimmune-response-induced de novo development of immune responses to self-antigens in the post-transplant period in the pathogenesis of chronic rejection following lung, heart, and kidney transplantation. This review details our current understanding of two distinct yet inter-dependent immune processes in the immunopathogenesis of chronic rejection. ... Read more

Abstract: The artificial antigen-presenting cells (AAPCs) described in this review were generated to facilitate the production of virus-specific T-cells for the treatment of infections in patients after bone marrow transplant. These AAPCs consist of murine 3T3 cells genetically modified to express critical human molecules needed for T-cell stimulation, such as the co-stimulatory molecules B7.1, ICAM-1, and LFA-3 and one of a series of 6 common HLA class I alleles. When T-cells were sensitized against cytomegalovirus (CMV) using AAPCs that express a shared HLA allele or using autologous antigen-presenting cells (APCs) loaded with the CMVpp65 antigen, they were activated and expanded to become HLA-restricted CMVpp65-specific T-cells. These T-cells demonstrated functional activity in vitro against CMV by producing IFNγ and inducing CMVpp65-specific cytotoxicity. T-cells sensitized with AAPCs recognized antigenic epitopes presented by each HLA allele known to be immunogenic in Man. Sensitization with AAPCs also permitted expansion of IFNγ+ cytotoxic T-cells against subdominant epitopes that were not effectively recognized by T-cells sensitized with autologous APCs. This panel of AAPCs provides a source of immediately accessible, standardizable, and replenishable "off the shelf" cellular reagents with the potential to make adoptive immunotherapy widely available for the treatment of lethal infections, cancer, and autoimmune diseases. ... Read more

Abstract: Type 1 diabetes is an autoimmune disease. Antigen-presenting cells process antigens, form a molecular complex with its own major histocompatibility complex (MHC) class II molecule, and present the complex to immune T cells. Type 1 diabetes, as in other autoimmune diseases may have MHC molecules that turn in self tissue components as the target for immune attack. Gene therapy is being explored to replace the self-inflicting MHC with one from a healthy donor. ... Read more

Abstract: Tumor suppresses immune functions. Immunotherapy with self immune cells taken from the body, empowered in petri dishes, and returned to the body remains a valuable means to contain tumor. The procedure for enhancing immune cells outside the body has not been efficient and reliable. Authors described an innovative technology to address the problem. ... Read more