Search

Introduction: An increasing number of patients present with multiple symptoms affecting many organs including the brain due to multiple mediators released by mast cells. These unique tissue immune cells are critical for allergic reactions triggered by immunoglobulin E (IgE), but are also stimulated (not activated) by immune, drug, environmental, food, infectious, and stress triggers, leading to secretion of multiple mediators often without histamine and tryptase. The presentation, diagnosis, and management of the spectrum of mast cell disorders are very confusing. As a result, neuropsychiatric symptoms have been left out, and diagnostic criteria made stricter excluding most patients. Areas covered: A literature search was performed on papers published between January 1990 and November 2018 using MEDLINE. Terms used were activation, antihistamines, atopy, autism, brain fog, heparin, KIT mutation, IgE, inflammation, IL-6, IL-31, IL-37, luteolin, mast cells, mastocytosis, mediators, mycotoxins, release, secretion, tetramethoxyluteolin, and tryptase. Expert opinion: Conditions associated with elevated serum or urine levels of any mast cell mediator, in the absence of comorbidities that could explain elevated levels, should be considered 'Mast Cell Mediator Disorders (MCMD).' Emphasis should be placed on the identification of unique mast cell mediators, and development of drugs or supplements that inhibit their release.

Introduction: Membranous nephropathy (MN) is the most common cause of a nephrotic syndrome in Caucasian adults. The identification of target antigens in MN in the last decade has had a major impact on the clinical approach to these patients. Areas covered: Since the discoveries in animal models in the 1980s that circulating autoantibodies induce disease upon in situ binding to glomerular podocytes, many attempts have been undertaken to define the human antigens responsible for disease induction. Only in 2009 was Phospholipase A2 Receptor 1 described as the major antigen responsible for MN onset in about 70% of patients. Subsequently, in 2014, Thrombospondin Type-1 Domain-Containing 7A was identified as a second antigen, accounting for 2-3% of patients with MN. The knowledge of the role of these antibodies in MN has improved the diagnosis and management of patients and helped to better define the need for immunosuppressive treatment. Expert commentary: These discoveries over the last 10 years in the discipline of nephrology have clearly shown the improvements a better understanding of disease pathogenesis can bring for patient care. [ABSTRACT FROM AUTHOR]

Introduction: Highly sensitized patients awaiting a kidney transplant accrue on the transplant waiting list. The breadth of HLA antibodies in this subpopulation of patients precludes receiving a compatible organ offer through regular allocation within an acceptable time-frame. Areas covered: Several alternative options to receive a transplant exist for these patients, including additional priority in regular allocation, special programs based on allocation through acceptable antigens, kidney paired donation programs, desensitization protocols, or a combination of the latter two. In this review, these options and their outcomes are discussed as well as some possibilities to further enhance transplantation of this disadvantaged group of patients. Expert commentary: For highly sensitized patients, special attention is required, for which several strategies may apply. A step-wise approach may be the optimal strategy to facilitate successful transplantation of highly sensitized patients. [ABSTRACT FROM AUTHOR]

Introduction: Adoptive therapy with chimeric antigen receptor (CAR) T cells redirected towards CD19 produces remissions of B cell malignancies, however, it also eradicates healthy B cells sharing the target antigen. Such ‘on-target off-tumor’ toxicity raises serious safety concerns when the target antigen is also expressed by tissue stem cells, with the risk of lasting tissue destruction. Areas covered: We discuss CAR T cell targeting of activation antigens versus lineage associated antigens on the basis of recent experimental and animal data and the literature in the field. Expert commentary: Targeting an activation associated antigen which is transiently expressed by stem cells seems to be safe, like CAR T cells targeting CD30 spare CD30+hematopoietic stem and progenitor cells while eliminating CD30+lymphoma cells, whereas targeting lineage associated antigens which increase in expression during cell maturation, like folate receptor-β and CD123, is of risk to destruct tissue stem cells. [ABSTRACT FROM AUTHOR]

Introduction: Hypersensitivity pneumonitis (HP) is an immunologically induced lung disease that develops after inhalation of certain environmental antigens only in subjects with susceptibility to antigens. Therefore, both environmental and host immunological factors play important roles in the aetiology and pathogenesis of HP. Areas covered: Determination of an inciting antigen is crucial for diagnosis, treatment and monitoring. For treatment, modification of the environment and of the host immune response are important. The former includes reduction of antigenic burden (i.e. disinfectant, cleaning), protective devices (i.e. filter, respiratory protection mask, ventilation) and avoidance of inciting antigens. The latter includes corticosteroids, lung transplantation and smoking cessation. For monitoring, measurement of serum Krebs von den Lungen (KL)-6 and surfactant protein (SP)-D concentrations can be used to screen for HP and to detect HP activity. Expert commentary: Measurement of an inciting antigen may be useful to predict the progression and prognosis of the disease. Treatment and monitoring are challenging in chronic HP with fibrosis. [ABSTRACT FROM PUBLISHER]

Over the past few years, the therapeutic potential of Treg has been highlighted in the field of autoimmune diseases and after allogeneic transplantation. The first hurdle for the therapeutic use of Treg is their insufficient numbers in non-manipulated individuals, in particular when facing strong immune activation and expanding effector cells, such as in response to an allograft. Here we review current approaches being explored for Treg expansion in the perspective of clinical therapeutic protocols. We describe different Treg subsets that could be suitable for clinical application, as well as discuss factors such as the required dose of Treg, their antigen-specificity and in vivo stability, that have to be considered for optimal Treg-based immunotherapy in transplantation. Since Treg may not be sufficient as stand-alone therapy for solid organ transplantation in humans, we draw attention to possible hurdles and combination therapy with immunomodulatory drugs that could possibly improve the in vivo efficacy of Treg. [ABSTRACT FROM AUTHOR]

Neonates have little immunological memory and a developing immune system, which increases their vulnerability to infectious agents. Recent advances in the understanding of neonatal immunity indicate that both innate and adaptive responses are dependent on precursor frequency of lymphocytes, antigenic dose and mode of exposure. Studies in neonatal mouse models and human umbilical cord blood cells demonstrate the capability of neonatal immune cells to produce immune responses similar to adults in some aspects but not others. This review focuses mainly on the developmental and functional mechanisms of the human neonatal immune system. In particular, the mechanism of innate and adaptive immunity and the role of neutrophils, antigen presenting cells, differences in subclasses of T lymphocytes (Th1, Th2, Tregs) and B cells are discussed. In addition, we have included the recent developments in the neonatal mouse immune system. Understanding neonatal immunity is essential to development of therapeutic vaccines to combat newly emerging infectious agents. [ABSTRACT FROM AUTHOR]