A genome-wide association study identifies new loci associated with response to SARS-CoV-2 mRNA-1273 vaccine in a cohort of healthy healthcare workers.

Introduction: The COVID-19 pandemic had significant global public health consequences, affecting over 200 countries and regions by 2020. The development and efficacy of specific vaccines, such as the mRNA-1273 (Spikevax) vaccine developed by Moderna Inc., have substantially reduced the impact of the pandemic and mitigated its consequences.

Identification of four autophagy-related genetic variants as risk factors for chronic lymphocytic leukemia.

We investigated the influence of 55,583 autophagy-related single nucleotide polymorphisms (SNPs) on chronic lymphocytic leukemia (CLL) risk across four independent populations comprising 5,472 CLL cases and 726,465 controls. We also examined their impact on overall survival (OS), time to first treatment (TTFT), autophagy flux, and immune responses. A meta-analysis of the four populations identified, for the first time, significant associations between CDKN2A (rs3731204) and BCL2 (rs4940571, rs12457371, rs1026825) SNPs and CLL risk, with CDKN2A showing the strongest association (p=1.

BCG-induced trained immunity potentiates TH17 responses in vitro.

Trained immunity amplifies innate immune responses in an antigen-independent manner. This study explored the ability of trained human primary macrophages to modulate the phenotype and function of T cells. Macrophages play an important role in antigen presentation, resulting in T-cell activation and antigen-specific clonal expansion; however, few studies have investigated whether trained immunity induction in macrophages modulates T cell activation.

Unveiling genetic signatures of immune response in immune-related diseases through single-cell eQTL analysis across diverse conditions.

Deciphering the intricate regulatory mechanisms underlying biological processes holds promise for elucidating how genetic variants contribute to immune-related disorders. We map genetic effects on gene expression (expression quantitative trait locus, eQTL) using single-cell transcriptomes of 152 samples from 38 healthy individuals, covering baseline state and lipopolysaccharide challenge either before or after Bacillus Calmette-Guerin vaccination. Interestingly, we uncover a monocyte eQTL linked to the LCP1, shedding light on inter-individual variations in trained immunity.

Polymorphisms within autophagy-related genes as susceptibility biomarkers for pancreatic cancer: A meta-analysis of three large European cohorts and functional characterization.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with patients having unresectable or metastatic disease at diagnosis, with poor prognosis and very short survival. Given that genetic variation within autophagy-related genes influences autophagic flux and susceptibility to solid cancers, we decided to investigate whether 55,583 single nucleotide polymorphisms (SNPs) within 234 autophagy-related genes could influence the risk of developing PDAC in three large independent cohorts of European ancestry including 12,754 PDAC cases and 324,926 controls. The meta-analysis of these populations identified, for the first time, the association of the BID variant with an increased risk of developing the disease (OR = 1.

Insights into the multifaceted role of interleukin-37 on human immune cell regulation.

Autoinflammatory diseases, while having a variety of underlying causes, are mediated by dysfunctional innate immune responses. Therefore, standard treatments target innate cytokines or block their receptors. Despite excellent responses in some patients, first-line treatments fail in others, for reasons which remain to be understood.

GPT-4 as a biomedical simulator.

Background: Computational simulation of biological processes can be a valuable tool for accelerating biomedical research, but usually requires extensive domain knowledge and manual adaptation. Large language models (LLMs) such as GPT-4 have proven surprisingly successful for a wide range of tasks. This study provides proof-of-concept for the use of GPT-4 as a versatile simulator of biological systems.

Citizen neuroscience: Wearable technology and open software to study the human brain in its natural habitat.

Citizen science allows the public to participate in various stages of scientific research, including study design, data acquisition, and data analysis. Citizen science has a long history in several fields of the natural sciences, and with recent developments in wearable technology, neuroscience has also become more accessible to citizen scientists. This development was largely driven by the influx of minimal sensing systems in the consumer market, allowing more do-it-yourself (DIY) and quantified-self (QS) investigations of the human brain.

Multi-omics analysis of innate and adaptive responses to BCG vaccination reveals epigenetic cell states that predict trained immunity.

Immune responses are tightly regulated yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live-attenuated vaccine induces not only an adaptive immune response against tuberculosis but also triggers innate immune activation and memory that are indicative of trained immunity.

Sex-specific association of visceral and subcutaneous adipose tissue volumes with systemic inflammation and innate immune cells in people living with obesity.

Background And Aims: Obesity predisposes to metabolic and cardiovascular diseases. Adipose tissue inflammation and systemic inflammation contribute to these complications. There are strong sex differences in adipose tissue distribution and in systemic inflammation.

The effect of leptin on trained innate immunity and on systemic inflammation in subjects with obesity.

Leptin is associated with cardiometabolic complications of obesity, such as metabolic syndrome and atherosclerosis. In obese men, the presence of metabolic syndrome is associated with higher circulating leptin and interleukin (IL)-6 concentrations and increased monocyte cytokine production capacity. Here, we investigated the effects of leptin on monocyte function and systemic inflammatory markers in obese individuals.

Polymorphisms within Autophagy-Related Genes as Susceptibility Biomarkers for Multiple Myeloma: A Meta-Analysis of Three Large Cohorts and Functional Characterization.

Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk.

GWAS-Identified Variants for Obesity Do Not Influence the Risk of Developing Multiple Myeloma: A Population-Based Study and Meta-Analysis.

Multiple myeloma (MM) is an incurable disease characterized by the presence of malignant plasma cells in the bone marrow that secrete specific monoclonal immunoglobulins into the blood. Obesity has been associated with the risk of developing solid and hematological cancers, but its role as a risk factor for MM needs to be further explored. Here, we evaluated whether 32 genome-wide association study (GWAS)-identified variants for obesity were associated with the risk of MM in 4189 German subjects from the German Multiple Myeloma Group (GMMG) cohort (2121 MM cases and 2068 controls) and 1293 Spanish subjects (206 MM cases and 1087 controls).

The impact of ADRB2 polymorphisms on immune responses and norepinephrine-induced immunosuppression.

Rationale: To evaluate whether common nonsynonymous variants [single-nucleotide polymorphisms (SNPs) or SNP haplotypes] in the β2-adrenergic receptor render subjects more susceptible to norepinephrine-induced immunosuppression and whether they are associated with dysregulated ex vivo and in vivo inflammatory responses.

Methods: Peripheral blood mononuclear cells from healthy volunteers (main cohort: n = 106, secondary cohort: n = 408) were ex vivo stimulated with various stimuli and production of cytokines was assessed. Additionally, ex vivo modulation of cytokine production by norepinephrine was evaluated in the main cohort.

Type 2 Diabetes-Related Variants Influence the Risk of Developing Prostate Cancer: A Population-Based Case-Control Study and Meta-Analysis.

In this study, we have evaluated whether 57 genome-wide association studies (GWAS)-identified common variants for type 2 diabetes (T2D) influence the risk of developing prostate cancer (PCa) in a population of 304 Caucasian PCa patients and 686 controls. The association of selected single nucleotide polymorphisms (SNPs) with the risk of PCa was validated through meta-analysis of our data with those from the UKBiobank and FinnGen cohorts, but also previously published genetic studies. We also evaluated whether T2D SNPs associated with PCa risk could influence host immune responses by analysing their correlation with absolute numbers of 91 blood-derived cell populations and circulating levels of 103 immunological proteins and 7 steroid hormones.

The gut microbiome as mediator between diet and its impact on immune function.

Dietary habits may affect inflammatory status in humans. Here we explore this interaction as well as the potential mediating role of the gut microbiome (GM), given that the GM is both involved in processing of dietary components and influences the immune system. A cross-sectional analysis of a sample of 482 healthy participants (207 males and 275 females) was performed.

Validation of GWAS-Identified Variants for Anti-TNF Drug Response in Rheumatoid Arthritis: A Meta-Analysis of Two Large Cohorts.

We aimed to validate the association of 28 GWAS-identified genetic variants for response to TNF inhibitors (TNFi) in a discovery cohort of 1361 rheumatoid arthritis (RA) patients monitored in routine care and ascertained through the REPAIR consortium and DANBIO registry. We genotyped selected markers and evaluated their association with response to TNFi after 6 months of treatment according to the change in disease activity score 28 (ΔDAS28). Next, we confirmed the most interesting results through meta-analysis of our data with those from the DREAM cohort that included 706 RA patients treated with TNFi.

The Immunological Factors Predisposing to Severe Covid-19 Are Already Present in Healthy Elderly and Men.

Male sex and old age are risk factors for COVID-19 severity, but the underlying causes are unknown. A possible explanation for this might be the differences in immunological profiles in males and the elderly before the infection. With this in mind, we analyzed the abundance of circulating proteins and immune populations associated with severe COVID-19 in 2 healthy cohorts.

Seasonal and Nonseasonal Longitudinal Variation of Immune Function.

Different components of the immune response show large variability between individuals, but they also vary within the same individual because of host and environmental factors. In this study, we report an extensive analysis of the immune characteristics of 56 individuals over four timepoints in 1 single year as part of the Human Functional Genomics Project. We characterized 102 cell subsets using flow cytometry; quantified production of eight cytokines and two chemokines in response to 20 metabolic, bacterial, fungal, and viral stimuli; and measured circulating markers of inflammation.