Adults With Congenital Heart Disease Have an Increased Prevalence of Autoimmunity.

Background: Adult congenital heart disease (ACHD) individuals have increased risk of noncardiac comorbidities including cancer and infections. Whether they are at increased risk of autoimmunity is unknown.

Objectives: The purpose of this study was to understand the association of ACHD and risk for autoimmunity.

Early diagnosis of axial spondyloarthritis among patients with chronic back pain using a clinical screening tool and referral strategy.

Objective: Lack of timely referral of suspected axial spondyloarthritis (axSpA) patients to rheumatologists is an important modifiable reason for diagnostic delay of axSpA. We assessed the usefulness of a self-referral strategy using a clinical feature-based screening questionnaire (SQ) (A-tool).

Methods: Finding axSpA (FaxSpA) was single-centre prospective study involving patients with chronic back pain (CBP).

Investigating cytotoxic and inflammatory human IL-7 receptor low effector memory CD8 T cells in lupus.

Background: This study aims to interrogate the implications of CD8 T cells in lupus by examining CD8 T cell heterogeneity and assessing the significance of this heterogeneity in promoting inflammation and tissue damage.

Methods: Our own and publicly available RNA-seq and microarray data from the peripheral blood and kidney tissues of patients with lupus were analysed. Imaging Mass Cytometry (IMC) analysis of immune cells was conducted in lupus and normal kidney tissues.

The tumor microenvironment of non-small cell lung cancer impairs immune cell function in people with HIV.

Lung cancer is the leading cause of cancer mortality among people with HIV (PWH), with increased incidence and poor outcomes. This study explored whether the tumor microenvironment (TME) of HIV-associated non-small cell lung cancer (NSCLC) limits tumor-specific immune responses. With a matched cohort of NSCLC samples from PWH and from people without HIV (PWOH), we used imaging mass cytometry, a linear mixed-effects model, and an artificial intelligence-based (AI-based) PageRank mathematical algorithm based on spectral graph theory to demonstrate that HIV-associated tumors have differential distribution of tumor-infiltrating CD8+ and CD4+ T cells, enriched for the expression of programmed cell death 1 (PD-1) and lymphocyte-activating gene 3 (LAG3), as well as activation and proliferation markers.

The clinical and socioeconomic aspects of t-cell receptor excision circle based newborn screening for severe combined immunodeficiency in Southeast and East Asia.

Severe Combined Immunodeficiency (SCID) is a widely underdiagnosed congenital disease that is fatal by 2-years old if left untreated. Most cases of SCID are diagnosed from the prompting of family history while other cases are sporadic and have no indicators for diagnosis besides the onset of debilitating infections. T-cell Receptor Excision Circle Newborn Screening (TREC NBS) offers an accessible way of flagging for SCID and other T-cell lymphopenia; however, the test implementation rate is low, particularly in Asian countries.

Association of clinical manifestations and immune alterations with genetic variants of uncertain significance in patients concerned for inborn errors of immunity.

Despite advances in genetic testing, Inborn Errors of Immunity (IEI) continue to present a diagnostic challenge, further complicated by genetic variants of uncertain significance (VUS). Therefore, this study evaluated associations of VUS with clinical and immunological characteristics in subjects with potential IEIs. Genes for which VUS were identified were clustered by distinct immune functions.

Decreased T helper 1 cell function underlies recurrent sinopulmonary infections in the 17q12 deletion syndrome.

Background: The 17q12 deletion syndrome (17q12DS) is a heterozygous deletion of a 1.4 megabase‒spanning DNA sequence on chromosome 17. The clinical characteristics of 17q12DS include neurodevelopmental disorders, kidney and urinary tract abnormalities.

Differences in immune cells and gene expression in human milk by parity on integrated scRNA sequencing.

Background: Human breast milk (HBM) is an important source of tolerogenic immune mediators that influence the infant immune system. HBM-derived immune components are affected by various factors; however, few studies have examined the relationship between parity and immune cell profiles of HBM.

Purpose: This study aimed to clarify the effects of parity on HBM immune cell heterogeneity and gene expression by integrating and analyzing publicly available single-cell RNAsequencing (scRNA-seq) datasets.

Expression of IL-7RαCX3CR1 CD8 T Cells and α4β7 Integrin Tagged T Cells Related to Mucosal Immunity in Children with Inflammatory Bowel Disease.

Purpose: The study aimed to investigate the recruiting of T lymphocytes including IL-7Rα CX3CR1 effector memory (EM) CD8 T cells and α4β7 integrin tagged T cells to inflamed intestinal mucosa.

Methods: Whole blood and mucosal tissues of intestine were collected from 40 children with or without inflammatory bowel disease (IBD). T cell surface staining and immunohistochemistry were done with several antibodies in peripheral blood mononuclear cells (PBMCs) and intestinal mucosa, respectively.

Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma.

Macrophage Migration Inhibitory Factor (MIF) and its homolog D-dopachrome Tautomerase (DDT) have been implicated as drivers of tumor progression across a variety of cancers. Recent evidence suggests MIF as a therapeutic target in immune checkpoint inhibition (ICI) resistant melanomas, however clinical evidence of MIF and particularly of DDT remain limited. This retrospective study analyzed 97 patients treated at Yale for melanoma between 2002-2020.

IL-1 receptor 1 signaling shapes the development of viral antigen-specific CD4 T cell responses following COVID-19 mRNA vaccination.

Background: The innate immune cytokine interleukin (IL)-1 can affect T cell immunity, a critical factor in host defense. In a previous study, we identified a subset of human CD4 T cells which express IL-1 receptor 1 (IL-1R1). However, the expression of such receptor by viral antigen-specific CD4 T cells and its biological implication remain largely unexplored.

Aging gene signature of memory CD8 T cells is associated with neurocognitive functioning in Alzheimer's disease.

Background: Memory CD8 T cells expand with age. We previously demonstrated an age-associated expansion of effector memory (EM) CD8 T cells expressing low levels of IL-7 receptor alpha (IL-7Rα) and the presence of its gene signature (i.e.

Natural isoaspartyl protein modification of ZAP70 alters T cell responses in lupus.

Protein posttranslational modifications (PTMs) arise in a number of normal cellular biological pathways and in response to pathology caused by inflammation and/or infection. Indeed, a number of PTMs have been identified and linked to specific autoimmune responses and metabolic pathways. One particular PTM, termed isoaspartyl (isoAsp or isoD) modification, is among the most common spontaneous PTM occurring at physiological pH and temperature.

Aging gene signature of IL-7 receptor alpha low effector memory CD8 T cells is associated with neurocognitive functioning in Alzheimer's disease.

CD45RA effector memory (EM) CD8 T cell expansion was reported in Alzheimer's disease (AD). Such cells are IL-7 receptor alpha (IL-7Rα) EM CD8 T cells, which expand with age and have a unique aging gene signature (i.e.

Changes in microRNAs during Storage and Processing of Breast Milk.

Human breast milk (HBM) is the ideal source of nutrients for infants and is rich in microRNA (miRNA). In recent years, expressed breast milk feeding rather than direct breastfeeding has become increasingly prevalent for various reasons. Expressed HBM requires storage and processing, which can cause various changes in the ingredients.

Implication of IL-7 receptor alpha chain expression by CD8 T cells and its signature in defining biomarkers in aging.

CD8 T cells play an important role in host defense against infections and malignancies as well as contribute to the development of inflammatory disorders. Alterations in the frequency of naïve and memory CD8 T cells are one of the most significant changes in the immune system with age. As the world population rapidly ages, a better understanding of aging immune function or immunosenescence could become a basis for discovering treatments of illnesses that commonly occur in older adults.

Effect of Androgen-Androgen Receptor Directed Therapy on COVID-19 Outcome in Prostate Cancer Patients.

TMPRSS2 is utilized by SARS-CoV-2 for cellular entry. Androgen-Androgen receptor directed therapy (A/ARDT) downregulates expression of TMPRSS2. We hypothesized A/ARDT might protect prostate cancer (PCa) patients from poor COVID-19 outcome.

Alterations in high-dimensional T-cell profile and gene signature of immune aging in HIV-infected older adults without viremia.

Alterations in the components of the immune system occur with aging. The introduction of combination antiretroviral therapy (ART) has dramatically improved life expectancy in human immunodeficiency virus (HIV) infected individuals by suppressing viral replication and increasing CD4 T-cell counts. Immunosenescence-like changes, including the expansion of memory CD8 T cells with senescent features, are reported in young HIV-infected individuals who do not have clinically detectable viremia on ART.

Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency.

Immune responses to coronavirus disease 2019 (COVID-19) mRNA vaccines in primary antibody deficiencies (PADs) are largely unknown. We investigated antibody and CD4 T-cell responses specific for SARS-CoV-2 spike protein (S) before and after vaccination and associations between vaccine response and patients' clinical and immunological characteristics in PADs. The PAD cohort consisted of common variable immune deficiency (CVID) and other PADs, not meeting the criteria for CVID diagnosis (oPADs).

No evidence of fetal defects or anti-syncytin-1 antibody induction following COVID-19 mRNA vaccination.

The impact of Coronavirus Disease 2019 (COVID-19) mRNA vaccination on pregnancy and fertility has become a major topic of public interest. We investigated 2 of the most widely propagated claims to determine (1) whether COVID-19 mRNA vaccination of mice during early pregnancy is associated with an increased incidence of birth defects or growth abnormalities; and (2) whether COVID-19 mRNA-vaccinated human volunteers exhibit elevated levels of antibodies to the human placental protein syncytin-1. Using a mouse model, we found that intramuscular COVID-19 mRNA vaccination during early pregnancy at gestational age E7.

T Cell Response to Influenza Vaccination Remains Intact in Adults with Congenital Heart Disease Who Underwent Early Thymectomy.

Introduction: T cells developed in the thymus play a key role in vaccine immunity. Thymectomy occurs during infant congenital heart surgery and results in an altered T cell distribution. We investigated if adults with congenital heart disease (ACHD) who underwent early thymectomy have a diminished response to influenza vaccination.

AHCC, a Standardized Extract of Cultured Lentinula Edodes Mycelia, Promotes the Anti-Tumor Effect of Dual Immune Checkpoint Blockade Effect in Murine Colon Cancer.

Treatment strategies combining immune checkpoint blockade (ICB) with other agents have emerged as a promising approach in the treatment of cancers. AHCC, a standardized extract of cultured mycelia, has been reported to inhibit tumor growth and enhance immune cell function. Here we investigated whether AHCC promotes the therapeutic effect of immunotherapy in cancers.