Comparison of COVID-19 Vaccine-Associated Myocarditis and Viral Myocarditis Pathology.

The COVID-19 pandemic has led to significant loss of life and severe disability, justifying the expedited testing and approval of messenger RNA (mRNA) vaccines. While found to be safe and effective, there have been increasing reports of myocarditis after COVID-19 mRNA vaccine administration. The acute events have been severe enough to require admission to the intensive care unit in some, but most patients fully recover with only rare deaths reported.

Autophagy and the Bone Marrow Microenvironment: A Review of Protective Factors in the Development and Maintenance of Multiple Myeloma.

The role of the unfolded protein response (UPR) in plasma cells (PC) and their malignant multiple myeloma (MM) counterparts is a well described area of research. The importance of autophagy in these cells, as well as the interplay between autophagy and the UPR system, has also been well studied. In this review, we will discuss the relationship between these two cellular responses and how they can be utilized in MM to account for the high levels of monoclonal immunoglobulin (Ig) protein synthesis that is characteristic of this disease.

Structural and Ultrastructural Analysis of the Multiple Myeloma Cell Niche and a Patient-Specific Model of Plasma Cell Dysfunction.

Multiple myeloma (MM) is a deadly, incurable malignancy in which antibody-secreting plasma cells (PCs) become neoplastic. Previous studies have shown that the PC niche plays a role cancer progression. Bone marrow (BM) cores from MM and a premalignant condition known as monoclonal gammopathy of unknown significance (MGUS) patients were analyzed with confocal and transmission electron microscopy.

Metabolomic Profiles of Men and Women Ischemic Stroke Patients.

Background: Stroke is known to affect both men and women; however, incidence and outcomes differ between them. Therefore, the discovery of novel, sex-specific, blood-based biomarkers for acute ischemic stroke (AIS) patients has the potential to enhance the understanding of the etiology of this deadly disease in the content of sex. The objective of this study was to identify serum metabolites associated with male and female AIS patients.

MHC haplotype and B cell autoimmunity: Correlation with pathogenic IgG autoantibody subclasses and Fc glycosylation patterns.

Genome-wide association studies (GWAS) have identified many genes that are associated with the development of certain autoimmune disorders, but the MHC haplotypes still represent the most prevalent genetic risk factor for many autoimmune diseases. The mechanisms by which MHC-associated genetic susceptibility translates into B cell autoimmunity and the development of autoimmune diseases are complex. There is increasing evidence that the MHC haplotype modulates autoreactive B cell responses in multiple ways.

Immunomodulatory regulation by heat-labile enterotoxins and potential therapeutic applications.

: Heat-labile enterotoxins (HLTs) and their cognate ganglioside receptors have been extensively studied because of their therapeutic potential. Gangliosides play arole in modulating effector cells of the immune system, and HLTs provide a novel means for stimulating ganglioside-mediated responses in immunocompetent cells.: To evaluate the mechanisms of HLT adjuvanticity, a systemic literature review was performed using relevant keyword searches of the PubMed database, accessing literature published as recently as late 2020.

Two Isolates Obtained From a Fatal Necrotizing Fasciitis Infection Display Distinct Genomic and Phenotypic Characteristics in Comparison to Type Strains.

has been recognized as a critical pathogen that causes severe infections worldwide not only because of the emergence of extensively drug-resistant (XDR) derivatives, but also because of its ability to persist in medical environments and colonize compromised patients. While there are numerous reports describing the mechanisms by which this pathogen acquires resistance genes, little is known regarding 's virulence functions associated with rare manifestations of infection such as necrotizing fasciitis, making the determination and implementation of alternative therapeutic targets problematic. To address this knowledge gap, this report describes the analysis of the NFAb-1 and NFAb-2 XDR isolates, which were obtained at two time points during a fatal case of necrotizing fasciitis, at the genomic and functional levels.

Efficacy of therapeutic plasma exchange in the treatment of penn class 3 and 4 cytokine release syndrome complicating COVID-19.

Objectives: Cytokine release syndrome (CRS) is a potentially severe complication of COVID-19 most commonly resulting in respiratory failure. This ten-patient study was designed to determine the efficacy of therapeutic plasma exchange (TPE) in improving oxygenation and in reducing the cytokine load in a critically ill subset of patients.

Methods: Five single volume plasma exchanges over eight days within a 14-day study period.

Key Players and Biomarkers of the Adaptive Immune System in the Pathogenesis of Sarcoidosis.

Sarcoidosis is a systemic inflammatory disease characterized by development of granulomas in the affected organs. Sarcoidosis is often a diagnosis of exclusion, and traditionally used tests for sarcoidosis demonstrate low sensitivity and specificity. We propose that accuracy of diagnosis can be improved if biomarkers of altered lymphocyte populations and levels of signaling molecules involved in disease pathogenesis are measured for patterns suggestive of sarcoidosis.

Immune response biomarkers as indicators of sarcoidosis presence, prognosis, and possible treatment: An Immunopathogenic perspective.

Sarcoidosis has been a disease of puzzling occurrence and clinical course. Multiple immunological markers have been noted to be altered within sarcoidosis, however there is variable consistency among these reports. Previous studies have shown sarcoidosis to be a primary T cell-mediated disease, yet new data concerning B cell and mycobacterial involvement have been brought to light.

Virus reactivation: a panoramic view in human infections.

Viruses are obligate intracellular parasites, relying to a major extent on the host cell for replication. An active replication of the viral genome results in a lytic infection characterized by the release of new progeny virus particles, often upon the lysis of the host cell. Another mode of virus infection is the latent phase, where the virus is 'quiescent' (a state in which the virus is not replicating).

Disturbed homeostasis and multiple signaling defects in the peripheral blood B-cell compartment of patients with severe chronic sarcoidosis.

The presence of hypergammaglobulinemia, autoantibodies, and circulating immune complexes suggests that humoral immunity may contribute to the pathogenesis of sarcoidosis. However, little is known about the role played by B cells in the development of this disease. Here we investigated the subpopulation distribution, response to stimulation, and levels of the nuclear transcription factor NF-κB/p65 in peripheral blood B cells from patients with severe chronic sarcoidosis.

Low levels of NF-κB/p65 mark anergic CD4+ T cells and correlate with disease severity in sarcoidosis.

T lymphocytes from patients with sarcoidosis respond weakly when stimulated with mitogen or antigen. However, the mechanisms responsible for this anergy are not fully understood. Here, we investigated the protein levels of nuclear transcription factor NF-κB (p50, p65, and p105), IκBα (inhibitor of NF-κB), T-cell receptor (TCR) CD3ζ-chain, tyrosine kinase p56(LCK), and nuclear factor of activated T cells c2 (NF-ATc2) in peripheral blood CD4(+) T cells from patients with sarcoidosis.

Cuba's kidney transplantation program.

The first kidney transplant in Cuba was performed on 24 February 1970, using a cadaveric donor. In 1979, living donor kidney transplantation began between first-degree relatives. A total of 2775 patients are enrolled in renal replacement therapy in 47 hospitals across the country, 1440 of whom are awaiting kidney transplantation.

Deletion of PPAR gamma in alveolar macrophages is associated with a Th-1 pulmonary inflammatory response.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is constitutively expressed at high levels in healthy alveolar macrophages, in contrast to other tissue macrophages and blood monocytes. PPARgamma ligands have been shown to down-regulate IFN-gamma-stimulated inducible NO synthase (iNOS) in macrophages. Because NO is an important inflammatory mediator in the lung, we hypothesized that deletion of alveolar macrophage PPARgamma in vivo would result in up-regulation of iNOS and other inflammatory mediators.

In vitro induction of immunoglobulin A (IgA)- and IgM-secreting plasma blasts by cholera toxin depends on T-cell help and is mediated by CD154 up-regulation and inhibition of gamma interferon synthesis.

Cholera toxin (CT) and the type II heat-labile enterotoxins (LT-IIa and LT-IIb) are potent immunological adjuvants which are hypothesized to enhance the production of antibody (Ab)-secreting cells, although their mechanisms of action are not fully understood. The treatment of splenic cells with concanavalin A (ConA) plus CT enhanced the production of immunoglobulin A (IgA) and IgM by dividing cells that expressed high levels of major histocompatibility complex class II (MHC-II), CD19, and CD138 and low levels of B220 a phenotype characteristic of plasma blasts. LT-IIa or LT-IIb moderately enhanced IgA and IgM production without enhancing plasma blast differentiation.

Mutants of type II heat-labile enterotoxin LT-IIa with altered ganglioside-binding activities and diminished toxicity are potent mucosal adjuvants.

The structure and function LT-IIa, a type II heat-labile enterotoxin of Escherichia coli, are closely related to the structures and functions of cholera toxin and LT-I, the type I heat-labile enterotoxins of Vibrio cholerae and enterotoxigenic Escherichia coli, respectively. While LT-IIa is a potent systemic and mucosal adjuvant, recent studies demonstrated that mutant LT-IIa(T34I), which exhibits no detectable binding activity as determined by an enzyme-linked immunosorbent assay, with gangliosides GD1b, GD1a, and GM1 is a very poor adjuvant. To evaluate whether other mutant LT-IIa enterotoxins that also exhibit diminished ganglioside-binding activities have greater adjuvant activities, BALB/c mice were immunized by the intranasal route with the surface adhesin protein AgI/II of Streptococcus mutans alone or in combination with LT-IIa, LT-IIa(T14S), LT-IIa(T14I), or LT-IIa(T14D).

Differential binding of Escherichia coli enterotoxins LT-IIa and LT-IIb and of cholera toxin elicits differences in apoptosis, proliferation, and activation of lymphoid cells.

Cholera toxin (CT), LT-IIa, and LT-IIb are potent adjuvants which induce distinct T-helper (Th)-cell cytokine profiles and immunoglobulin G (IgG) subclass and IgA antibody responses. To determine if the distinct immune regulatory effects observed for LT-IIa, LT-IIb, and CT are elicited by binding of the enterotoxins to their cognate ganglioside receptors, the lineages of lymphoid cells that interact with the three enterotoxins and their effects on various lymphocyte responses in vitro were evaluated. Binding patterns of LT-IIa, LT-IIb, and CT to several lymphoid cell populations were distinctive for each enterotoxin.

Mucosal adjuvant properties of mutant LT-IIa and LT-IIb enterotoxins that exhibit altered ganglioside-binding activities.

LT-IIa and LT-IIb, the type II heat-labile enterotoxins of Escherichia coli, are closely related in structure and function to cholera toxin and LT-I, the type I heat-labile enterotoxins of Vibrio cholerae and E. coli, respectively. Recent studies from our group demonstrated that LT-IIa and LT-IIb are potent systemic and mucosal adjuvants.

Regulation of CXCR3 and CXCR4 expression during terminal differentiation of memory B cells into plasma cells.

C-X-C motif chemokine receptor 3 (CXCR3) and CXCR4 expressed on immunoglobulin G (IgG)-plasma-cell precursors formed in memory immune responses are crucial modulators of the homing of these cells. Here, we studied the regulation of the expression of these chemokine receptors during the differentiation of human memory B cells into plasma cells. We show that CXCR3 is absent on CD27- naive B cells but is expressed on a fraction of memory B cells, preferentially on those coexpressing IgG1.

CD38 low IgG-secreting cells are precursors of various CD38 high-expressing plasma cell populations.

Despite the important role immunoglobulin G (IgG)-secreting plasma cells play in memory immune responses, the differentiation and homeostasis of these cells are not completely understood. Here, we studied the differentiation of human IgG-secreting cells ex vivo and in vitro, identifying these cells by the cellular affinity matrix technology. Several subpopulations of IgG-secreting cells were identified among the cells isolated from tonsils and bone marrow, particularly differing in the expression levels of CD9, CD19, and CD38.

Plasma cell survival is mediated by synergistic effects of cytokines and adhesion-dependent signals.

Recent results suggest that plasma cell longevity is not an intrinsic capacity, but depends on yet unknown factors produced in their environment. In this study, we show that the cytokines IL-5, IL-6, TNF-alpha, and stromal cell-derived factor-1alpha as well as signaling via CD44 support the survival of isolated bone marrow plasma cells. The cytokines IL-7 and stem cell factor, crucially important for early B cell development, do not mediate plasma cell survival, indicating that plasma cells and early B cells have different survival requirements.

The role of long-lived plasma cells in autoimmunity.

Recent results on the biology of plasma cells have shown that these cells can survive as long as memory B cells. Possibly, such long-lived plasma cells are also involved in the production of autoantibodies. Here, we discuss the potential involvement of long-lived plasma cells in the pathogenesis of autoimmune disease and the consequences it has for the development of effective therapeutic strategies.

Chemotactic responsiveness toward ligands for CXCR3 and CXCR4 is regulated on plasma blasts during the time course of a memory immune response.

Plasma blasts formed during memory immune responses emigrate from the spleen to migrate into the bone marrow and into chronically inflamed tissues where they differentiate into long-lived plasma cells. In this study, we analyze the chemokine responsiveness of plasma blasts formed after secondary immunization with OVA. Starting from day 4 and within approximately 48 h, OVA-specific plasma blasts emigrate from spleen and appear in the bone marrow.

Humoral immunity and long-lived plasma cells.

A selected fraction of plasmablasts enters the compartment of nondividing, long-lived plasma cells to maintain humoral antibody memory. In accord with a current model for lymphocyte homeostasis, the lifetime of long-lived plasma cells is probably regulated by competition for a limited number of survival niches present in splenic red pulp, bone marrow and inflamed tissue. Plasma cells secreting autoantibodies specific for some, but not all, self-antigens are probably 'allowed' to enter the compartment of long-lived plasma cells and provide antibody-mediated 'autoimmune memory' that is resistant to conventional therapies.