Current Immunology Reviews (Discontinued) - Volume 14, Issue 2, 2018

Osteoarthritis results from a chronic inflammation-mediated destruction of synovial joints particularly in the hand, hip, and knee. Intervention strategies primarily focus on reducing this inflammation and its associated pain and involve a hierarchy of pharmaceuticals designed to prolong activity and prevent early joint replacement. Unfortunately, side effects from these agents are significant and their efficacy, especially in the later stages of the condition, variable. For this reason, many patients are seeking out alternative interventions, including herbal medicines, which are natural and safe. This review will evaluate the current understanding of the pathophysiology and immunological changes that occur in osteoarthritis and identify areas where herbal medicines could improve treatment strategies.

Genetics has become increasingly important in disease prevention, diagnosis and treatments. Currently, molecular sequencing within medically important genes such as those coded for human leukocyte antigens, blood group and killer cell immunoglobulin-like receptors has been elucidated and their sequence variations have been deposited in public databases (e.g. allelefrequencies.net database). In addition, medical genetic research has now gained access to the unlimited region in the human genome where multiple susceptibility genes can now easily be characterized using the latest techniques in molecular biology (next generation sequencing and Luminex). Here, we highlight molecular bases of several variants in cytokine genes that have been widely subjected to the analyses of ancestry and health. We also demonstrate how an understanding of population data may have significant values in improving human health.

The emergence of immunotherapies in the field of oncology has improved outcomes and given hope to patients with cancer diagnoses that have traditionally carried a poor prognosis. Specifically, Immune Checkpoint Inhibitors (ICIs), target Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA-4) and Programmed Cell Death 1 (PD-1), all of which have key roles in regulating the immune response. Manipulation of these immune checkpoint pathways allows the body to exert a greater antitumor response but this unrestricted immune response comes with an array of Autoimmune Related Adverse Events (IRAEs). The most commonly reported IRAEs are generally nonlife threatening and include fatigue, pruritus, diarrhea, and rash. In the literature, there have been a growing number of case reports detailing cardiotoxicity in patients receiving ICIs. Unlike the more common IRAEs, ICI induced cardiotoxicity is associated with greater mortality. This article aims to describe the plausible mechanisms of ICI related cardiotoxicity as well as strategies for clinicians to recognize and manage cardiotoxicity. As immunotherapy based treatment strategies continue to widen and the population of patients receiving these agents expands, increasing provider awareness of potentially fatal toxicities will continue to be an important issue.

In cancer immunotherapy, Natural Killer (NK) cells have achieved prominence. NK cells were identified in the 1970s as a subgroup of lymphocytes containing larger cytoplasmic granules. These cells are widely distributed in all lymphoid and non-lymphoid tissues, including bone marrow, lymph nodes, the spleen, peripheral blood, the lungs and liver. Because they do not present gene rearrangements during their ontogeny, they constitute a lineage of innate lymphoid cells. Immunotherapy in cancer has been reported with the use of Interleukin (IL) for the NK cell induction in clinical trials, which are discussed in this review. IL-treated NK cells directly kill target tumor cells through at least four mechanisms, the release of cytoplasmic granules, death receptor-induced apoptosis, production of effector molecules, or antibody-dependent cytotoxicity. More recently, Chimeric Antigen Receptor (CAR) gene transfer to primary NK cells or the human NK-92 cell line has been used to introduce new therapeutic options. The genetic manipulation of NK cells objected to the expression of CARs, allowing them to recognize tumor-specific antigens associated with increased survival, proliferation and cytotoxicity. Although there are advances in cancer immunotherapy, new therapies targeting tumor cells are required, as well as NK cell survival in tumor microenvironments, increase in their antitumor activity and immunosuppressive T cells control.

Autoinflammatory Disorders (AIDs) can be either systemic or organ-specific. Systemic AIDs are associated with a primary dysfunction of the innate immunity that results in clinical signs of inflammation and/or elevated serum levels of acute-phase reactants. AIDs often present with rash, serositis, arthritis and/or aphthosis. Hereditary periodic fever syndromes, such as Familial Mediterranean Fever (FMF) and Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), constitute the prototype of systemic AIDs. However, these also include many other disorders that do not follow the typical relapse-remitting pattern of unprovoked recurrent febrile episodes with intercalated periods of general well-being that can also result in severe complications such as amyloidosis. In this review, previous classification systems of AIDs, either clinical or pathophysiological/functional-based, have been revised and systemic AIDs are individually described. Also, a simplified classification based on clinical phenotypes that differentiates systemic from organ-specific AIDs is discussed.

Lambert-Eaton Myasthenic Syndrome (LEMS) is a very rare and unusual autoimmune disorder of Neuromuscular Junction (NMJ) that is associated with impaired neuromuscular transmission due to loss of voltage-gated calcium channel (VGCC) present on the pre-synaptic nerve terminal. Of all the different proteins like synaptotagmin that are attacked by auto-antibodies, P/Q-type of VGCC is found to be targeted in 90 % of patients. The influx of calcium through VGCC is important for exocytosis of synaptic vesicles. LEMS is a clinical “triad” of proximal muscle weakness, areflexia, and autonomic dysfunctions. Half of the LEMS patients are almost always associated with the small-cell lung carcinoma (SCLC), the knowledge of which has led to the finding of different paraneoplastic, and non-tumor related neurological disorders of the central nervous system. The rest of the people present idiopathic LEMS. The repetitive nerve stimulation is the electrophysiological study that is the diagnostic test of choice. The diagnostic confirmation of LEMS is always followed by prompt screening of SCLC majorly by radiological screenings. Prognosis depends on the presence of SCLC and severity of weakness. If carcinoma is not found, symptomatic therapy is done but none of the drugs confer complete normalcy in symptoms. The supra-additive effect of amifampridine and GV-58 shown in pre-clinical trials is the anticipated long-run prospect in the LEMS treatment. A PubMed literature search was conducted by using keywords: “Lambert-Eaton”, “Myasthenic”, and “Syndrome”. A total of 1067 articles were found. A further selection of articles was made by excluding the non-relevant articles.

Background: Fish is one of the most common causes of IgE-mediated adverse reactions to food. Several allergens have been identified and characterized from different fish species, among them, parvalbumin, as a highly conserved protein, is the most common causative agent of fish-borne allergies. Although most fish-allergic patients are sensitive to various species, some patients only show hypersensitivity to certain species such as salmonids. In this study, we computationally identified and mapped mono-sensitivity-causing Epitopes of salmonid fish and their cross-reactive Epitopes using in silico methods. Methods: Amino acid sequences of parvalbumins were retrieved from NCBI, and following alignment, the phylogenic tree was drawn and potential Epitopes were determined and their physicochemical properties analyzed. Results: We found that fish-allergic patients are mostly sensitized to beta-1 isoform of parvalbumin and its epitope C region (65-109) in salmonids is probably the causative agent of monosensitivity, while in beta-2 isoforms it may justify cross-reactivity of parvalbumins. Conclusion: Surely, any progresses in biochemical, immunological, and molecular mechanism of allergic reactions to fish allergens can improve accurate diagnosis of fish allergy and its' prevention and treatment in the future.