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Animal models are a key element in disease research and treatment. In the field of neuropsychiatric lupus research, inbred, transgenic and disease-induced mice provide an opportunity to study the pathogenic routes of this multifactorial illness. In addition to achieving a better understanding of the immune mechanisms underlying the disease onset, supplementary metabolic and endocrine influences have been discovered and investigated. The ever-expanding knowledge about the pathologic events that occur at disease inception enables us to explore new drugs and therapeutic approaches further and to test them using the same animal models. Discovery of the molecular targets that constitute the pathogenic basis of the disease along with scientific advancements allow us to target these molecules with monoclonal antibodies and other specific approaches directly. This novel therapy, termed 'targeted biological medication' is a promising endeavor towards producing drugs that are more effective and less toxic. Further work to discover additional molecular targets in lupus' pathogenic mechanism and to produce drugs that neutralize their activity is needed to provide patients with safe and efficient methods of controlling and treating the disease. © The Author(s), 2016.

Human papillomavirus vaccine (HPVv) is used worldwide for prevention of infection. However several reports link this vaccine, with immune-mediated reactions, especially with neurological manifestations. Our previous results showed that HPVv-Gardasil and aluminum-immunized mice developed behavioral impairments. Studies have shown a positive effect of phospholipid supplementation on depression and cognitive functions in mice. Therefore, our goal was to evaluate the effect of a dietary supplement on vaccine-induced depression. Sixty C57BL/6 female mice were immunized with HPVv-Gardasil, aluminum or the vehicle (n = 20 each group), and half of each group were fed 5 times per week with 0.2 ml of a dietary supplement enriched with phosphatidylcholine. The mice were evaluated for depression at 3 months of age, by the forced swimming test. Both the Gardasil and the aluminum-treated mice developed depressive-like behavior when compared to the control group. The HPVv-Gardasil-immunized mice supplemented with phosphatidylcholine significantly reduced their depressive symptoms. This study confirms our previous studies demonstrating depressive-like behavior in mice vaccinated with HPVv-Gardasil. In addition, it demonstrates the ability of phosphatidylcholine-enriched diet to attenuate depressive-like behavior in the HPVv-Gardasil-vaccinated mice. We suggest that phosphatidylcholine supplementation may serve as a treatment for patients suffering vaccine-related neurological manifestations. © 2016, Springer Science+Business Media New York.

Vaccine adjuvants and vaccines may induce autoimmune and inflammatory manifestations in susceptible individuals. To date most human vaccine trials utilize aluminum (Al) adjuvants as placebos despite much evidence showing that Al in vaccine-relevant exposures can be toxic to humans and animals. We sought to evaluate the effects of Al adjuvant and the HPV vaccine Gardasil versus the true placebo on behavioral and inflammatory parameters in female mice. Six-week-old C57BL/6 female mice were injected with either, Gardasil, Gardasil + pertussis toxin (Pt), Al hydroxide, or, vehicle control in amounts equivalent to human exposure. At 7.5 months of age, Gardasil and Al-injected mice spent significantly more time floating in the forced swimming test (FST) in comparison with vehicle-injected mice (Al, p = 0.009; Gardasil, p = 0.025; Gardasil + Pt, p = 0.005). The increase in floating time was already highly significant at 4.5 months of age for the Gardasil and Gardasil + Pt group (p ? 0.0001). No significant differences were observed in the number of stairs climbed in the staircase test which measures locomotor activity. These results indicate that differences observed in the FST were unlikely due to locomotor dysfunction, but rather due to depression. Moreover, anti-HPV antibodies from the sera of Gardasil and Gardasil + Pt-injected mice showed cross-reactivity with the mouse brain protein extract. Immunohistochemistry analysis revealed microglial activation in the CA1 area of the hippocampus of Gardasil-injected mice. It appears that Gardasil via its Al adjuvant and HPV antigens has the ability to trigger neuroinflammation and autoimmune reactions, further leading to behavioral changes. © 2016, Springer Science+Business Media New York.

The major histocompatibility complex system is the most polymorphic gene cluster of the mammal genome. In humans, this is a genomic locus known as the human leukocyte antigen (HLA) system. The HLA encodes mostly immune-associated proteins whose main effect is the presentation of antigens to the immune cells. Thus, it is clear that it is essential for to the proper function of the immune response against pathogens and strongly implicated in the development of autoimmune diseases. Nonetheless, there are hundreds of polymorphisms of HLA-DRB1 which have been associated with different autoimmune disorders as well as with immune response to infection and vaccines. It is possible that the interaction of specific HLA with pathogenic antigens is one of the keys favoring (or protecting) toward the development of an autoimmune disease. In the era of personalized medicine, it would be of great help to build a map of the genomic risk of each individual to evaluate the risk of developing an autoimmune condition. © 2016, Springer Science+Business Media New York.

Neuropsychiatric lupus affects above 50% of patients with systemic lupus erythematosus and may span from mild symptoms to acute devastating life-threatening ones. Owing to the clinical variability, most pharmacological data rely on small, uncontrolled trials and case reports. The mainstay of therapy relies on immune-suppression by glucocorticoids, in adjunction with cyclophosphamide or anti-B-cell therapy, in moderate to severe cases. In selected scenarios (e.g., chorea) intravenous immunoglobulin or plasmapheresis may be effective. Anticoagulation is warranted if anti-phospholipid antibodies are present. In parallel there may be a need for symptomatic treatment such as anti-epileptic or anti-depressive treatments, etc. In the future, more studies addressed to assess pathogenesis and preferred treatments of specific manifestations are needed in order to personalize treatments. © 2015 Taylor and Francis.

Hepatitis-B vaccine (HBVv) can prevent HBV-infection and associated liver diseases. However, concerns regarding its safety, particularly among patients with autoimmune diseases (i.e. SLE) were raised. Moreover, the aluminum adjuvant in HBVv was related to immune mediated adverse events. Therefore, we examined the effects of immunization with HBVv or alum on SLE-like disease in a murine model.NZBWF1 mice were immunized with HBVv (Engerix), or aluminum hydroxide (alum) or phosphate buffered saline (PBS) at 8 and 12 weeks of age. Mice were followed for weight, autoantibodies titers, blood counts, proteinuria, kidney histology, neurocognitive functions (novel object recognition, staircase, Y-maze and the forced swimming tests) and brain histology.Immunization with HBVv induced acceleration of kidney disease manifested by high anti-dsDNA antibodies (. p less than 0.01), early onset of proteinuria (. p less than 0.05), histological damage and deposition of HBs antigen in the kidney. Mice immunized with HBVv and/or alum had decreased cells counts mainly of the red cell lineage (. p less than 0.001), memory deficits (. p less than 0.01), and increased activated microglia in different areas of the brain compare with mice immunized with PBS. Anxiety-like behavior was more pronounced among mice immunized with alum.In conclusion, herein we report that immunization with the HBVv aggravated kidney disease in an animal model of SLE. Immunization with either HBVv or alum affected blood counts, neurocognitive functions and brain gliosis. Our data support the concept that different component of vaccines may be linked with immune and autoimmune mediated adverse events. © 2014 Elsevier Ltd.

Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and cataplexy (a sudden weakening of posture muscle tone usually triggered by emotion) caused by the loss of orexin neurons in the hypothalamus. Autoimmune mechanisms are implicated in narcolepsy by increased frequency of specific HLA alleles and the presence of specific autoantibody (anti-Tribbles homolog 2 (TRIB2) antibodies) in the sera of patients with narcolepsy. Presently, we passively transferred narcolepsy to naïve mice by injecting intra-cerebra-ventricularly (ICV) pooled IgG positive for anti-TRIB2 antibodies. Narcolepsy-IgG-injected mice had a loss of the NeuN (neuronal marker), synaptophysin (synaptic marker) and orexin-positive neurons in the lateral hypothalamus area in narcolepsy compared to control-IgG-injected mice and these changes were associated with narcolepsy-like immobility attacks at four weeks post injection and with hyperactivity and long term memory deficits in the staircase and novel object recognition tests. Similar behavioral and cognitive deficits are observed in narcoleptic patients. This is the first report of passive transfer of experimental narcolepsy to naïve mice induced by autoantibodies and supports the autoimmune pathogenesis in narcolepsy. © 2013 Elsevier Ltd.