Pharmacokinetics/pharmacodynamics by race: Analysis of a peginterferon β-1a phase 1 study.

Background: Black/African American participants are underrepresented in clinical trials for multiple sclerosis but can experience a greater burden of disease than other racial groups in the United States. A phase 1, open-label, crossover study that demonstrated bioequivalence of subcutaneous and intramuscular injection of peginterferon β-1a in healthy volunteers enrolled similar proportions of Black and White participants, enabling a post hoc subgroup analysis comparing these groups.

Methods: Peginterferon β-1a (125 μg) was administered by subcutaneous or intramuscular injection, followed by a washout period before a second injection using the alternative method.

The Minority Scientists' Experience: Challenging and Overcoming Barriers to Enhancing Diversity and Career Advancement.

Minority groups face barriers in accessing quality health care, professional advancement, and representation in immunology research efforts as a result of institutional racism that if unaddressed can perpetuate a lack of diversity. In 2021, the AAI Minority Affairs Committee convened a cross section of academic and industry scientists from underrepresented groups at various stages of their professions to discuss how best to address the toll racism takes on study design and scientific careers. Panelists drew directly from their own experiences as scientists to share perspectives and strategies for countering a lack of representation in clinical research, responding to microaggressions, navigating academic advancement, and providing effective mentorship.

Bioequivalence of intramuscular and subcutaneous peginterferon beta-1a: results of a phase I, open-label crossover study in healthy volunteers.

Background: Peginterferon beta-1a administered every 2 weeks subcutaneous (SC) injection is approved to treat adult patients with relapsing-remitting multiple sclerosis (RRMS) and relapsing forms of multiple sclerosis (RMS). However, associated injection site reactions (ISRs) can lead to treatment discontinuation. Prior studies with interferon beta-1a reported a lower frequency of ISRs with intramuscular (IM) administration than with SC administration.

Organotypic Brain Slice Culture Microglia Exhibit Molecular Similarity to Acutely-Isolated Adult Microglia and Provide a Platform to Study Neuroinflammation.

Microglia are central nervous system (CNS) resident immune cells that have been implicated in neuroinflammatory pathogenesis of a variety of neurological conditions. Their manifold context-dependent contributions to neuroinflammation are only beginning to be elucidated, which can be attributed in part to the challenges of studying microglia and the lack of tractable systems to study microglia function. Organotypic brain slice cultures offer a tissue-relevant context that enables the study of CNS resident cells and the analysis of brain slice microglial phenotypes has provided important insights, in particular into neuroprotective functions.

Prime-boost strategies to embrace diversity and inclusion in immunology.

Immunologists appreciate the need for creative approaches to tackle complex scientific questions, which can involve not only the use of novel technologies but also the experience of scientists from diverse backgrounds. Here, we highlight measures to prime for the inclusion of women and underrepresented individuals in science to boost immunology research.

B-Cell Depletion Promotes Aortic Infiltration of Immunosuppressive Cells and Is Protective of Experimental Aortic Aneurysm.

Objective: B-cell depletion therapy is widely used for treatment of cancers and autoimmune diseases. B cells are abundant in abdominal aortic aneurysms (AAA); however, it is unknown whether B-cell depletion therapy affects AAA growth. Using experimental models of murine AAA, we aim to examine the effect of B-cell depletion on AAA formation.

Compounded Bioidentical Hormones in Endocrinology Practice: An Endocrine Society Scientific Statement.

This Scientific Statement finds that there is no rationale for routine prescribing of unregulated, untested, and potentially harmful custom compounded bioidentical hormone therapies.

Fcγ receptor dependency of agonistic CD40 antibody in lymphoma therapy can be overcome through antibody multimerization.

Immunomodulatory mAbs, led by the anti-CTLA4 mAb ipilimumab, are an exciting new class of drugs capable of promoting anticancer immunity and providing durable control of some tumors. Close analysis of a number of agents has revealed a critical yet variable role for Fcγ receptors in their efficacy. In this article, we reveal that agonistic anti-CD40 mAbs have an absolute requirement for cross-linking by inhibitory FcγRIIB when used systemically to treat established BCL1 syngeneic lymphoma, and therapy is lost when using a mouse IgG2a mAb not cross-linked by FcγRIIB.

Anti-CD20 as the B-Cell Targeting Agent in a Combined Therapy to Modulate Anti-Factor VIII Immune Responses in Hemophilia a Inhibitor Mice.

Neutralizing antibody formation against transgene products can represent a major complication following gene therapy with treatment of genetic diseases, such as hemophilia A. Although successful approaches have been developed to prevent the formation of anti-factor VIII (FVIII) antibodies, innovative strategies to overcome pre-existing anti-FVIII immune responses in FVIII-primed subjects are still lacking. Anti-FVIII neutralizing antibodies circulate for long periods in part due to persistence of memory B-cells.

Immunotherapy targeting inhibitory Fcγ receptor IIB (CD32b) in the mouse is limited by monoclonal antibody consumption and receptor internalization.

Genetic deficiency of the inhibitory Fc receptor, FcγRIIB (CD32b), has been shown to augment the activity of activatory FcγR and promote mAb immunotherapy. To investigate whether mAbs capable of blocking FcγRIIB have similar capacity, we recently generated a panel of specific anti-mouse FcγRIIB mAbs that do not cross-react with other FcRs, allowing us to study the potential of FcγRIIB as a therapeutic target. Previous work revealed a number of these mAbs capable of eliciting programmed cell death of targets, and in the present study we demonstrated their ability to promote target cell phagocytosis.

Intercommunication between the neuroendocrine and immune systems: focus on myasthenia gravis.

Crosstalk exists between the nervous, endocrine, and immune systems, and perturbations in these interactions have been associated with disease. This includes production of neuroendocrine factors that alter immune system activity and increase susceptibility to or severity of immune-related conditions, such as myasthenia gravis (MG)--a T-cell-dependent, B-cell-mediated autoimmune disorder. MG results from impairment of transmission to the neuromuscular junction and involves the thymus--especially in early-onset disease, but the exact mechanism by which the thymus impacts disease is unclear.

Tissue expression of steroid hormone receptors is associated with differential immune responsiveness.

Glucocorticoids have been used as treatments against a number of diseases, especially autoimmune/inflammatory conditions in which the immune system is overactive. These treatments have varying degrees of responsiveness among individuals and in different tissues (including brain); therefore, it is important to determine what could account for these differences. In this study, we evaluated expression of stress hormone receptors in immune cells from lymphoid and non-lymphoid tissues (including brain) as a possible explanation.

Flow cytometry as a tool for measurement of steroid hormone receptor protein expression in leukocytes.

Measurement of protein expression in live, intact cells using flow cytometry (FC) has been employed for several decades in the areas of immunology, cell biology, and molecular biology. More recently, this technique has found appreciation in applied scientific fields, including cancer biology and endocrinology, to serve as a tool for identifying cells more likely to respond to specific treatments. FC, also referred to as fluorescence-activated cell sorting (FACS), is an antibody-based method that provides the user with an ability to identify proteins expressed on surfaces of cells as well as in the cytoplasm, including steroid hormone receptors.

Inhibitory effects of progesterone differ in dendritic cells from female and male rodents.

Background: Steroid hormones, such as progesterone, are known to have immunomodulatory effects. Our research group previously reported direct effects of progesterone on dendritic cells (DCs) from female rodents. Primarily affecting mature DC function, progesterone effects included inhibition of proinflammatory cytokine secretion, downregulation of cell surface marker (major histocompatibility complex class II, CD80) expression, and decreased T-cell proliferative capacity, and were likely mediated through progesterone receptor (PR) because the PR antagonist RU486 reversed these effects.

The role of glucocorticoids and progestins in inflammatory, autoimmune, and infectious disease.

A bidirectional communication exists between the CNS and the immune system. The autonomic nervous system, through neurotransmitters and neuropeptides, works in parallel with the hypothalamic-pituitary-adrenal axis through the actions of glucocorticoids to modulate inflammatory events. The immune system, through the action of cytokines and other factors, in turn, activates the CNS to orchestrate negative-feedback mechanisms that keep the immune response in check.

Neuroendocrine factors alter host defense by modulating immune function.

An increasing body of evidence demonstrates that there is bidirectional communication between the neuroendocrine and immune systems. Interaction between these systems results in a variety of outcomes, including the well documented "sickness behavior" elicited by cytokines of the immune system that can enter the brain and activate second messengers that modify neuronal activity. Crosstalk between the neuroendocrine and immune systems can also result in production of factors by the nervous and endocrine systems that alter immune cell function and subsequent modulation of immune responses against infectious agents and other pathogens.

Evaluation of steroid hormone receptor protein expression in intact cells using flow cytometry.

Several methods are currently employed to evaluate expression of steroid hormone receptors in tissues and cells, including real-time reverse-transcriptase polymerase chain reaction (real-time RT-PCR) and western blot assays. These methods require homogenization of cells, thereby preventing evaluation of individual cells or specific cell types in a given tissue sample. In addition, methods such as real-time RT-PCR assess mRNA levels, which may be subject to posttranslational modifications that prevent subsequent production of functional proteins.

Progesterone inhibits mature rat dendritic cells in a receptor-mediated fashion.

A variety of extraimmune system factors, including hormones, play a critical role in regulating immunity. Progesterone has been shown to affect immunity in rodents and humans, mainly at concentrations commensurate with pregnancy. These effects are primarily mediated via the progesterone receptor (PR), which acts as a transcription factor, although non-genomic effects of PR activation have been reported.

Pilot study of Flt3 ligand comparing intraperitoneal with subcutaneous routes on hematologic and immunologic responses in patients with peritoneal carcinomatosis and mesotheliomas.

Purpose: This study compared the clinical toxicity and hematological effects of i.p. and s.