Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) - Volume 3, Issue 1, 2016

Influenza virus A (IAV) once established into the host can trigger a broad spectrum of immune responses. In this respect, innate immunity contributes to host pro- tection against IAV either via activation of epithelial cells and phagocytes or release of mediators such as antiviral peptides and cytokines. On the other hand, antigen presenta- tion by dendritic cells, T helper cell involvement and T cytotoxic-mediated adaptive functions complete the initial defense mounted by innate immunity. Despite the host robust immune response against IAV, this virus is also able to promote escape mechanisms. In fact, evidence has been provided that both type I and type II interferons candampen phagocytic responses against IAV. Besides that, T regulatory (Treg) cells, when hyper-activated, can also depress the primary immune response against IAV. On these bases, natural products can be beneficial in the treatment of IAV infection for their capacity to regulate im- munity as well as the intestinal microbiota composition. Prebiotics and probiotics are used in the case of IAV infections in ageing which is very often complicated by co-infections. Polyphenols act as anti-inflammatory substances, thus activating Treg cell function via production of interleukin-10. According to the dynamics of immune response against IAV, activation of Treg cells can be advantageous for the host in the later phase of infection in order to reduce lung immunopathology.

Influenza is a major public health problem worldwide. Epidemiological and virological surveillance has been demonstrated to be crucial for prevention of both seasonal and pandemic influenza. Recent influenza seasons have been characterized by the circulation of the strain A(H1N1)pdm09. It was identified for the first time in 2009 and accounted for the most recent influenza pandemic. In spite of moderate mortality rates observed during 2009 influenza pandemic, quite interestingly severe cases of influenza by the new pandemic strain A(H1N1)pdm09 were more frequent in young adults, who were previously healthy and free of risk factors. Of note, dissemination of influenza A(H3N2) virus with both antigenic and genetic drifts was mostly predominant in 2014-2015 influenza season. The variant A/Switzerland/9715293/2013(H3N2) replaced A/Texas/50/2012(H3N2) in vaccine formulation of season 2015-2016. Recent influenza seasons in South Italy (Apulia region) were characterized by lower and later incidence peaks respect to those of Northern Italy probably due to differences in climate. Influenza vaccine coverage rates in Apulia steadily declined in general population, especially in individuals ≥ 65 years, creating concern in health authorities. Avian influenza viruses (AIVs) such as H5N1, H7N9, H9N2 and H10N8 are able to disseminate to domestic poultry and then to humans from natural sources. Therefore, these viruses are considered as emerging with a special concern related to their potential to cause next influenza pandemic.

Although influenza vaccination remains the most effective way to protect the population from infection, current Flu vaccines induce suboptimal immune responses in particular segments of the population and need to be reformulated almost every year due to the genetic instability of the virus. The development of next generation Flu vaccines represents a fascinating challenge for scientists and clinicians, who aim to design new vaccine formulations that are able to induce cross-protective immunity against multiple influenza strains and promote long-lasting immune responses. With this review we discuss the promising strategies that currently are being evaluated for the development of next-generation Flu vaccines, and the therapeutic approaches that have been tested to fight ongoing infections.

Over 40 years have passed since the discovery of its effectiveness in bladder cancer, and intravesical bacillus Calmette-Guerin (BCG) immunotherapy remains the mainstay for the treatment of non-muscle-invasive bladder cancer. Although efforts have been made to elucidate the mechanisms, those for BCG actions against bladder cancer are not fully understood. Nonetheless, it is now suggested that most of BCG effects are due to stimulation of immune system, leading to local host immune reactions and eventual cancer cell death. It is also likely that BCG has direct cytotoxic effects. The purpose of this review is to gather available data regarding the cascade of changes in urothelial cancer cells following exposure to BCG as well as to discuss the lacking information in the current literature.

In obesity, the immune cell-adipocyte axis in the context of white adipose tissue (WAT) represents a source of several mediators, such as adipokines, cytokines and chemokines. Within WAT, both innate and adaptive immune cells contribute to a condition of low grade inflammation, which, in turn, accounts for obesity-associated complications. In this review, the effects of natural products and probiotics on WAT cells will be illustrated. Polyphenols are ubiquitously present in the vegetal kingdom and, when assumed with diet or as supplements, they exert anti-inflammatory effects also acting upon WAT cells. Vitamin A and vitamin D, thanks to their receptors dis- tributed on several cell types, are able to modulate WAT cell functions. Polyunsatu- rated fatty acids are also endowed with anti-obesogenic activities, acting upon the immune cell-adipocyte axis. Finally, probiotics are able to correct the altered obese microbiota, partici- pating to the interplay between immune cells and adipocytes.

Type I diabetes (T1D) is an organ-specific autoimmune disease that targets on the destruction of insulin-producing pancreatic β cells. Many strategies, including immunosuppressive and antigen-specific immunoregulatory therapies, have been per- formed in animal models and in the clinic to prevent and treat T1D. Among them, induction of regulatory T cells (Treg) specific to β cell-associated autoantigens (BAA) for T1D therapy provides several advantages, including specificity and lasting effica- cy in controlling unrestricted autoimmunity. In this review, we discuss the progression of applying autoantigen-specific Treg cells in treating T1D, hoping to provide some useful information for future clinicians to develop more effective and safe antigen- specific immunoregulatory therapies on T1D treatment.

Background: The study focused on a new dietary approach to treatment of diet-related immune pathologies interesting an increasing number of people sensi- tive to dietary antigens like gluten or nickel. In particular we paid particular atten- tion to pathological condition that is a combination of two frequent conditions not still perfectly known: gluten-related syndrome defined as non-celiac gluten sensitivi- ty (NCGS) and systemic (gastrointestinal and skin) reactions to ingestion of nickel rich food that characterizes Systemic Nickel Allergy Syndrome (SNAS). Objective: The aim of this study was to implement a new exclusion diet (DICE diet) in patients with the mentioned pathologies. Usually, for this condition, diet is represented by a list of forbidden food that doesn't consider the initial weight. This is why there is a loss of the adherence of patients to the diet as a consequence of efficacy of treatment. Method: The new exclusion diet is developed, keeping in mind, the initial weight, considering the gen- eral patient's state to ensure the respect for a sufficient time in order to reduce symptoms. The compliance and the effects on the weight have been detected by a questionnaire during the 6-month follow up. Results: 17 patients, with SNAS and NCGS, have been treated with the DICE diet and after 6 months, 70% of them have reported symptoms disappearance. Conclusion: We suggest that the DICE diet could be prescribed for the treatment of these diet-related immune-pathologies.

Introduction: Spasticity is the most important problem in the recovery of a satisfactory function of the upper limb to the patient outcomes of cerebral stroke. Objective of the study is to compare the results in functional recovery in patients treated with botulinum toxin A and occupational therapy and patients treated with botulinumtoxinA, occupational therapy (OT) and functional electrical stimulation (FES) (Ness H-200). Materials and methods: 36 Patients (middle aged 55.25 ± 6.5) with spasticity of the upper limbs for more than six months and in particular with the involvement of the muscles of the hand. Patients were divided into two groups: Group I underwent botulinumtoxinA-occupational therapy-functional electrical stimulation; Group II underwent botuli- numtoxinA and occupational therapy. All patients were evaluated with the modified Ashworth scale, with the measurement of the passive ROM, the evaluation of the amplitude of the compound action po- tential of the median nerve (registration site in the flexor digitorum superficial) and ARAT test at the time T0 (recruitment and infiltration), T1 (20 days after first infiltration), T2 (3 months after first infil- tration), T3 (four months after first infiltration; we reinjected botulinumtoxinA), T4 (20 days after sec- ond infiltration), T5 (3 months after second infiltration), T6 ( four months after first infiltration; we reinjected botulinum toxin A). Result: Group treated with botulinumtoxinA-OT-FES showed a statistically significant improvement com- pared to the other group in the evaluation of the passive ROM, in the assessment of spasticity with the modified Ashworth scale, in the reduction of the amplitude cMAP of the median nerve and in the score of ARAT test. Conclusion: The application of the FES joined to treatment with botulinumtoxinA and OT proves ef- fective synergy for greater functional recovery of the upper limb and the best possible outcomes.

Introduction: Coronary vasculitis in patients with ANCA associated vas- culitides is underestimated and occurs most frequently in Granulomatosis with Pol- yangiitis. The objective was to review the outcome of patients treated for coronary vasculitis under our care. Methods: We retrospectively reviewed the management and outcome on all patients with ANCA associated vasculitis and coronary involvement under nephrology follow up at Universiti Kebangsaan Malaysia Medical Centre between 2008 and 2013. These pa- tients were referred to us for renal involvement of their systemic vasculitides. Results: Three out of 13 the patients with ANCA associated vasculitides developed coronary vasculitis. These patients (2 males: 1 female), aged 37, 48 and 57 years old developed coro- nary vasculitis at least 3 months from the initial presentation of systemic vasculitides. Although all pa- tients developed coronary vasculitis after receiving immunosuppressive treatment, therapy was limited by concurrent/preceding infections. Coronary vasculitis was diagnosed based on ECG changes, elevated cardiac biomarkers and echocardiogram findings with evidence of active vasculitis as supported by in- flammatory markers and auto antibodies. All three patients died either due to a coronary event or over- whelming infection secondary to immunosuppressive therapy. Conclusion: Coronary vasculitis is underreporrted in pateints with ANCA associated vasculitis. Early recognition and treatment are crucial as it carries a high cardiovascular morbidity and mortality.

Amyotrophic Lateral Sclerosis (ALS) is an unknown pathogenesis pro- gressive neurodegenerative disease of the central nervous system that leads to death within 1-5 years. Clinically, it is often possible to find at the level of the lower limbs some clinical manifestations of damage of the I motor neuron with spastic paralysis, iperflexia and clonus, with impairment of the ability of patients' deambulation and their management of the activities of daily living (such as personal hygiene or dressing). So, the first therapeutic approach in these patients are antispasmodic drugs orally and after Botulinum toxin type A injection (BTX-A). Aim of this study is to demonstrate the efficacy of BTX-A in patients with ALS and spasticity of lower limbs no responder to the treatment with oral antispastic drugs with no adverse events. We enrolled 5 patients (3 female and 2 male); they were evaluated at baseline (T0, before BTX- A treatment), and over the following three months with three follow-up visits (T1 30 days after the infil- tration, T2 60 days after infiltration and T3 90 days after infiltration) with myometric measure of tone, Modified Ashworth Scale, Barthel Index, Adductor Tone Rating Scale and Hygiene Score. We treated the adductor muscles (AM) of patients with incobotulinum toxin type A (Xeomin®, Merz) with ultra- sound guide. We obtained an improvement of spasticity with miometric measurement, Modified Ash- worth Scale, Barthel Index, Adductor Tone Rating Scale and Hygiene Score for 90 days after injection (p<0,05). Our preliminary study shows the possibility to use BTX-A in the treatment of the spasticity in patients with ALS no responders to oral antispastic drugs, with no side effects.