Immune dysfunction in chronic kidney disease

Chronic kidney disease is characterized by immune dysfunction that increases predisposition to infections, virus-associated cancers and impaired response to vaccination. The altered immune response is caused by impairment of both innate and adaptive immune systems, as well as other factors that are hallmarks of renal disease, such as uremia, malnutrition, chronic inflammation, mineral bone disease and anemia. The aim of this article is to review the causes and mechanisms that lead to immune dysfunction in patients with chronic kidney disease.

Higher exhaled nitric oxide at 6 weeks of age is associated with less bronchiolitis and wheeze in the first 12 months of age

BackgroundNitric oxide in exhaled air (eNO) is used as a marker of type 2 immune response-induced airway inflammation. We aimed to investigate the association between eNO and bronchiolitis incidence and respiratory symptoms in infancy, and its correlation with eosinophil protein X (EPX).MethodsWe followed up infants at 6 weeks of age born to mothers with asthma in pregnancy and measured eNO during natural sleep using a rapid response chemiluminescense analyser (CLD88; EcoMedics), collecting at least 100 breaths, interpolated for an expiratory flow of 50 mL/s. EPX normalised to creatinine was measured in urine samples (uEPX/c). A standardised questionnaire was used to measure symptoms in first year of life. Associations were investigated using multiple linear regression and robust Poisson regression models.ResultseNO levels were obtained in 184 infants, of whom 125/184 (68%) had 12 months questionnaire data available and 51/184 (28%) had uEPX/c measured. Higher eNO was associated with less respiratory symptoms during the first 6 weeks of life (n=184, ß-coefficient: –0.49, 95% CI –0.95 to –0.04, p=0.035). eNO was negatively associated with uEPX/c (ß-coefficient: –0.004, 95% CI –0.008 to –0.001, p=0.021). Risk incidence of bronchiolitis, wheeze, cold or influenza illness and short-acting beta-agonist use significantly decreased by 18%–24% for every unit increase in eNO ppb.ConclusionHigher eNO levels at 6 weeks of age may be a surrogate for an altered immune response that is associated with less respiratory symptoms in the first year of life.

Case Report: Serial Cases: Prolongation of High Immunoglobulin G Level in Repetitive COVID-19 Convalescence Plasma Donor in Saiful Anwar Hospital Malang, Indonesia

BackgroundConvalescent plasma therapy is expected to be a promising alternative to supportive therapy during the SARS-CoV-2 pandemic outbreak. Altered immune response in repetitive convalescent plasma donors has not been widely studied. This case series was reported to analyze the patterns of immune responses and the factors that might influence them in repetitive convalescent plasma donors and increase awareness of COVID-19 survivors to donate their convalescent plasma.Cases IllustrationThere were five repetitive donors who were eligible as convalescent plasma donor requirements. It was found two donors who showed increment of anti-SARS-CoV-2 IgG level after donation and two others who showed persistent anti-SARS-CoV-2 IgG level more than two months after recovered.DiscussionThere was a difference in immune response in survivors who have the probability of being exposed to same antigens with survivors who did not, where the group of survivors who are at risk of exposure to antigens after recovery could trigger anamnestic immune response that can increase antiSARS-CoV-2 IgG levels. The other factor that influence the prolongation of anti-SARS-CoV-2 IgG levels are the possibility of neutralizing antibodies in plasma upregulation.ConclusionImmunological phenomenon in SARS-CoV-2, both in survivors and convalescent plasma donors, have not been widely observed and studied. From the case series discussed above, it can be concluded that convalescent plasma donation does not yet have strong evidence of decreasing levels of specific antibodies against SARS-CoV-2 and plasmapheresis procedure is safe to be done without reducing the protective effect of donor antibody post-plasma donation.

COVID-19 and the Incidence of Acute Myocardial Injury

Cardiovascular manifestations are frequent in COVID-19 infection and are predictive of adverse outcomes. Elevated cardiac biomarkers are common findings in patients with cardiovascular comorbidities and severe COVID-19 infection. Troponin, inflammatory and thrombotic markers may also improve risk prediction in COVID-19. In our comprehensive review, we provide an overview of the incidence, potential mechanisms and outcome of acute cardiac injury in COVID-19. Thereby, we discuss coagulation abnormalities in sepsis and altered immune response as contributing factors favoring myocardial injury. We further highlight the role of endothelial damage in the pathophysiological concepts. Finally, observational studies addressing the incidence of myocardial infarction during COVID-19 pandemic are discussed.

Enterocytozoon Bieneusi Infects Children With Inflammatory Bowel Disease Undergoing Immunosuppressive Treatment

Objectives: Patients with inflammatory bowel disease (IBD) are susceptible to intestinal opportunistic infections due to both defective mucosal immunity and altered immune response resulting from immunosuppressive treatment. Microsporidia infecting the gastrointestinal tract and causing diarrhoea can potentially affect the course of IBD.Methods: Stool samples (90 IBD children and 121 healthy age-matched controls) were screened for Encephalitozoon spp. and Enterocytozoon bieneusi by microscopy and polymerase chain reaction followed by sequencing.Results:E. bieneusi genotype D was found in seven out of 90 (7.8%) IBD children. No children from the control group were infected, making the pathogen prevalence in the IBD group significant (P = 0.002). Furthermore, infection was confirmed only in patients receiving immunosuppressive treatment (P = 0.013).Conclusions: Children with IBD are at risk of intestinal E. bieneusi infection, especially when receiving immunosuppressive treatment. Therefore, microsporidia should be considered as a significant infectious agent in this group of patients.

VACCINATION PARADOXES IN OBESITY

The review article discusses the problem of post-vaccination immune response in children obesity and adults with infections, in particular with COVID-19. Changes in various cellular and humoral immunity links in the experiment and in the clinic, associated with chronic inflammation and metabolic disregulation that accompanies obesity, are revealed. People with obesity, who are at higher risk of developing infections, may have an altered immune response to vaccination. Research is needed to study post-vaccination immunity in obesity, including an assessment of the possible impact of comorbidities on the vaccination of individual microbiota.

Immune transcriptomes from hospitalized patients infected with the SARS-CoV-2 variants B.1.1.7 and B.1.1.7 carrying the E484K escape mutation

Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. B.1.1.7 (VOC-202012/01) has become the predominant variant in many countries and a new lineage (VOC-202102/02) harboring the E484K escape mutation in the B.1.1.7 background emerged in February 2021. This variant is of concern due to reduced neutralizing activity by vaccine-elicited antibodies. However, it is not known whether this single amino acid change leads to an altered immune response. Here, we investigate differences in the immune transcriptome in hospitalized patients infected with either B.1.1.7 (n=28) or B.1.1.7+E484K (n=12). RNA-seq conducted on PBMCs isolated within five days after the onset of COVID symptoms demonstrated elevated activation of specific immune pathways, including JAK-STAT signaling, in B.1.1.7+E484K patients as compared to B.1.1.7. Longitudinal transcriptome studies demonstrated a delayed dampening of interferon-activated pathways in B.1.1.7+E484K patients. Prior vaccination with BNT162b vaccine (n=8 one dose; n=1 two doses) reduced the transcriptome inflammatory response to B.1.1.7+E484K infection relative to unvaccinated patients. Lastly, the immune transcriptome of patients infected with additional variants (B.1.258, B.1.1.163 and B.1.7.7) displayed a reduced activation compared to patients infected with B.1.1.7. Acquisition of the E484K substitution in the B.1.1.7 background elicits an altered immune response, which could impact disease progression.

Molecular Mechanisms of Atopic Dermatitis Pathogenesis

Atopic dermatitis is a chronic, non-infectious inflammatory dermatosis. Acharacteristic feature is persistent itching of the skin. The chronic, relapsing course of the disease, economic burden, and the whole family’s involvement in the treatment process immensely reduce the quality of life of patients and their families. The disease emerges as a social problem by increasing indirect costs, such as visiting a doctor, absenteeism from work and school, and avoiding social interactions. Thepathophysiology of atopic dermatitis is complex and multifactorial. It includes genetic disorders, a defect in the epidermal barrier, an altered immune response, anddisruption of the skin’s microbial balance. The numerous complex changes at thegenetic level and innate and adaptive immunity provide the basis for characterizing the various phenotypes and endotypes of atopic dermatitis. Emerging therapies rely on the action of specific molecules involved in the disease’s pathogenesis. It may be the starting point for the individualization of atopic dermatitis treatment. This paper will try to present some molecular mechanisms of atopic dermatitis and their clinical implications.