Function of Protein S-Palmitoylation in Immunity and Immune-Related Diseases

Protein S-palmitoylation is a covalent and reversible lipid modification that specifically targets cysteine residues within many eukaryotic proteins. In mammalian cells, the ubiquitous palmitoyltransferases (PATs) and serine hydrolases, including acyl protein thioesterases (APTs), catalyze the addition and removal of palmitate, respectively. The attachment of palmitoyl groups alters the membrane affinity of the substrate protein changing its subcellular localization, stability, and protein-protein interactions. Forty years of research has led to the understanding of the role of protein palmitoylation in significantly regulating protein function in a variety of biological processes. Recent global profiling of immune cells has identified a large body of S-palmitoylated immunity-associated proteins. Localization of many immune molecules to the cellular membrane is required for the proper activation of innate and adaptive immune signaling. Emerging evidence has unveiled the crucial roles that palmitoylation plays to immune function, especially in partitioning immune signaling proteins to the membrane as well as to lipid rafts. More importantly, aberrant PAT activity and fluctuations in palmitoylation levels are strongly correlated with human immunologic diseases, such as sensory incompetence or over-response to pathogens. Therefore, targeting palmitoylation is a novel therapeutic approach for treating human immunologic diseases. In this review, we discuss the role that palmitoylation plays in both immunity and immunologic diseases as well as the significant potential of targeting palmitoylation in disease treatment.

Runx Transcription Factors in T Cells—What Is Beyond Thymic Development?

Runx proteins (also known as Runt-domain transcription factors) have been studied for a long time as key regulators of cellular differentiation. RUNX2 has been described as essential for osteogenesis, whereas RUNX1 and RUNX3 are known to control blood cell development during different stages of cell lineage specification. However, recent studies show evidence of complex relationships between RUNX proteins, chromatin-modifying machinery, the cytoskeleton and different transcription factors in various non-embryonic contexts, including mature T cell homeostasis, inflammation and cancer. In this review, we discuss the diversity of Runx functions in mature T helper cells, such as production of cytokines and chemokines by different CD4 T cell populations; apoptosis; and immunologic memory acquisition. We then briefly cover recent findings about the contribution of RUNX1, RUNX2 and RUNX3 to various immunologic diseases. Finally, we discuss areas that require further study to better understand the role that Runx proteins play in inflammation and immunity.

Covid-19 Pandemic Era: Is It Time To Promote Home Dialysis And Peritoneal Dialysis?

ABSTRACT The novel coronavirus, called SARS-CoV-2 has been declared a pandemic on March 2020, by the World Health Organization. Older individuals and patients with comorbid conditions such as hypertension, heart disease, diabetes, lung disease, chronic kidney disease (CKD), and immunologic diseases are at higher risk of contracting this severe infection. In particular, patients with advanced CKD constitute a vulnerable population and a challenge in the prevention and control of the disease. Home-based renal replacement therapies offer opportunity to manage patients remotely, thus reducing the likelihood of infection due to direct human interaction. Patients are seen less frequently, limiting the close interaction between patients and healthcare workers who may contract and spread the disease. On the other hand, while home dialysis is reasonable selection at his time due to the advantage of isolation of patients, measures must be assured to implement the program. Despite its logistical benefits, outpatient hemodialysis also presents certain challenges during times of crises such as COVID 19 pandemic and potentially future ones.

Climate Change and Human Health: A Review of Allergies, Autoimmunity and the Microbiome

The impact of climate change on human health is a topic of critical importance. While only recently beginning to gain attention, it is clear that immediate action is necessary to minimize this impact. In our review, we will outline a subset of these effects in detail. We will examine how climate change has worsened respiratory allergic disease. We will discuss how climate change has altered antigen exposure, possibly disrupting antigen-specific tolerance by the immune system, leading, in turn, to an increase in the prevalence of immunologic diseases. Finally, we will explore how the loss of biodiversity related to climate change may affect the microbiome, potentially leading to dysbiosis, inflammatory, autoimmune and neurologic diseases.

Certolizumab-Induced Paradoxical Psoriatic Alopecia

Introduction: Biologic drugs have revolutionized the treatment of chronic inflammatory immunologic diseases. However, their use is associated with adverse reactions, including paradoxical adverse events. Tumor necrosis factor (TNF)–associated psoriatic alopecia (TiAPA) is a paradoxical adverse event that has been rarely reported in the literature. Only 1 case secondary to certolizumab has been recently described. Case Presentation: We described a case of scalp alopecia secondary to certolizumab in a 27-year old female patient with Crohn disease. The skin biopsy showed psoriasiform changes and loss of sebaceous lobule compatible with TiAPA. The patient presented significant improvement in the clinical findings and hair regrowth after 4 weeks of treatment with clobetasol unguent 0.05% and discontinuation of certolizumab. Months later she received infliximab for her Crohn disease, achieving good control of the illness until today. Discussion: This is a paradoxical adverse event that has been rarely reported in the literature. Most of the cases were related with infliximab and adalimumab. There is no standard approach for the management of TNF inhibitor–induced psoriasis, but around 20% require discontinuation of treatment. Conclusions: The recognition of anti-TNF drug–induced alopecia has allowed description of a new form of alopecia, clinically and histologically mimicking primary psoriatic alopecia with the recently described finding of loss of sebaceous lobules. Recognizing this form of alopecia can enable effective treatment while allowing, in most cases, anti-TNF therapy to continue.

Sex and Glomerular Filtration Rate Trajectories in Children

Background and objectivesDifferences in CKD progression by sex have been hypothesized to explain disparities in access to kidney transplantation in children. This study aims to identify distinct trajectories of eGFR decline and to investigate the association of sex with eGFR decline.Design, setting, participants, & measurementsWe used data from the CKD in Children study. Latent class mixed models were used to identify eGFR trajectories and patient characteristics were compared between trajectories. Progression was studied to two outcomes: ESKD (dialysis or transplantation) and a combined outcome of ESKD or 50% eGFR decline from baseline, using multivariable parametric failure time models.ResultsAmong 888 patients, 613 with nonglomerular and 275 with glomerular diseases, we observed four and two distinct GFR trajectories, respectively. Among patients with nonglomerular diseases, there was a higher proportion of males in the group with a low baseline GFR. This group had an increased risk of ESKD or 50% GFR decline, despite a similar absolute decline in GFR. Eight patients with nonglomerular diseases, mostly males with obstructive uropathies, had a more rapid absolute GFR decline. However, the association between male sex and rapid absolute GFR decline was NS after adjustment for age, baseline GFR, and proteinuria. Among patients with glomerular diseases, a subgroup including mostly females with systemic immunologic diseases or crescentic GN had a rapid absolute GFR decline.ConclusionsThis study identifies different trajectories of CKD progression in children and found a faster progression of CKD in females in patients with glomerular diseases, but no significant sex difference in patients with nonglomerular diseases. The differences in progression seem likely explained by sex differences in the underlying primary kidney disease and in baseline GFR rather than by a direct effect of sex on progression.