bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Immune Pathologies Are Common in Azerbaijan
Authors: Fazal Nadeem , Ibrahimova Shalala , Mammadova Vafa , Aliyeva Gunay , Nasrullayeva Gulnara 
Published: January 2023

Abstract
Genetic immune pathologies are common in Azerbaijan. Primary immune deficiencies (PID) include more than 300 rare congenital diseases. There are more than 250 genes known to be involved in different immune disorders, especially in PID. Around 30% of patients are not diagnosed on time despite having clinical and laboratory evidences. Primary immunodeficiency disorders may be caused by mutations in one or several specific genes. The exact diagnosis of PID patients requires genetic analysis. The diagnosis is not always made timely because genetic tests are not carried out in many countries like Azerbaijan and are quite expensive. We present data of clinical and genetic analyses PIDs in Azerbaijan. During 2010–2019 we studied 111 PID patients. Genetic results obtained from 18 of these patients revealed that the mutations were located mainly in 7 groups of genes. These genetic mutations had clinical manifestations in the form of PID variants, i.e., WAS syndrome, X link agammaglobulinemia, HIGM syndrome, and Ataxia-Telangiectasia. AT patients were analyzed through linkage analysis with D11S384, D11S2179 and D11S1294 genetic markers. Immune analyses included; phenotyping of leucocyte subset in peripheral blood, serum IgM, IgG, IgA, IgE levels, phagocytic activity of neutrophils by NBT. Additional tests such as X-ray, computer tomography and ultrasound investigations were used. Genotyping of mutations was performed through sequence-based methods. In PID patients mutations in the following genes were identified; CCCG&gt;C deletion on TBX1 gene, c.12_13insGG hemizygous mutation on exon 1 of WAS gene, Gln234stop mutation and T&gt;A SNP on 100614289 location of BTKgene, c.6010C&gt;T and c.6671G&gt;A mutations on LRBAgene, c.135T&gt;A on CD40LGgene.
Glucocorticoid induced leucine zipper is inversely related with neuroinflammation in the brain
Authors: Lynch Nicholas McChesney , Wong Junmei , Srinivasan Mythily 
Published: January 2023

Abstract
Glucocorticoids (GC) are steroid hormones secreted as the end-product of the neuroendocrine stress cascade. Absence or elevated GC mediate neurotoxic responses, suggesting that a narrow window ranging from physiological to slightly high GC mediate protective responses. The beneficial effects are attributed to the transactivation of regulatory proteins and inhibition mediated by glucocorticoid receptor interactions with other cofactors. Elevated GC accelerate beta amyloid (Aβ ) plaque formation and tau phosphorylation, aggregates of which upregulate reactive oxygen species in vulnerable neurons. The oxidative stress negatively regulates glucocorticoid receptor, preventing suppression of the transcriptional factor, nuclear factor-κ B (NF-κ B) by GC. The ensuing inflammatory distress enhance further Aβ accumulation initiating a vicious cycle. The glucocorticoid induced leucine zipper (GILZ) is a gene strongly upregulated by GC and mediates many of the anti-inflammatory and anti-proliferative effects of GC. Mechanistically GILZ inhibits NF-κ B by binding the p65 subunit of NF-κ B in the cytoplasm and thereby prevent transactivation of inflammatory and apoptosis mediators. Although GILZ is constitutively expressed in many tissues including the brain, the expression has been shown to occur with varying dynamics suggesting that the local milieu modulates its expression with consequent effects on cellular responses. Here we investigated the expression profile of GILZ in lipopolysaccharide mediated neuroinflammation model of Alzheimer’s disease. Our data suggest that the GILZ expression is downregulated in neuroinflammation correlating inversely with the pro-inflammatory cytokines and innate immune responses.
Adaptive immune cell activation in acute pediatric traumatic brain injury
Authors: Ortega Sterling B , Torres Vaneesa O , Tian Fenghua , Poinsatte Katie , Tweed Jefferson , Greenwell Cynthia , Windsor Jana , Raman Lakshmi , Miles Darryl , Stowe Ann 
Published: January 2023

Abstract
Traumatic brain injury (TBI) is mediated by mechanical injury to the brain resulting in tissue shearing, and characterized by neuronal injury and inflammation. We hypothesize that TBI activates brain-targeting immune responses which can induce secondary neuronal injury. Blood and cerebral spinal fluid (external ventricular drain, EVD) were collected from pediatric TBI patients (pTBI, 1–18 yrs.) at days 1, 3 and 5 following TBI and EVD placement. The blood from sick controls (0–18 yrs, no CNS injury) were collected at day 1 post injury. pTBI patients exhibited a higher quantity of leukocytes (CD45+) relative to controls (p=0.01) on day 1 post-TBI, indicating an immediate and robust immune modulation due to CNS injury, that decreased at days 3 and 5, relative to day 1. Major subsets of adaptive immune cells (CD3, CD4, CD8, and CD19) did not exhibit altered cellularity relative to controls but activated adaptive T cells (CD4+CD161+and CD8+CD161+) were substantially higher at day 1 versus controls. Neuronal autoreactivity was evaluated by labeling peripheral blood mononuclear cells with carboxyfluorescein succinimidyl ester (CFSE) and culturing with neuronal and control antigens. Response to antigen was determined by dilution of CFSE (proliferation) and expression of CD25 (activation). Autoreactivity analysis of pTBI patients revealed a decrease in the CD4 T-cell responses to CNS antigens relative to sick control patients. Interestingly, the CD8 T-cell analysis revealed CNS-specific autoimmune responses absent in pTBI patients which were present in sick controls. Based on these initial observations, we hypothesize that the adaptive immune system is activated upon TBI and can potentially target CNS resident cells in young patients.
Coronary artery bypass grafting surgery is associated with immunoparalysis of monocytes and dendritic cells
Authors: Perros Alexis J , Esguerra-Lallen Arlanna , Rooks Kelly , Chong Fenny N , Engkilde-Pedersen Sanne , Faddy Helen M , Hewlett Elise , Naidoo Rishendran , Tung John-Paul , Fraser John F , Tesar Peter , Ziegenfuss Marc , Smith Susan , O'Brien Donalee , Flower Robert L , Dean Melinda M 
Published: January 2023

Abstract

Background
Exposure of patient blood to the bypass circuitry and re-perfusion of the heart at the end of coronary artery bypass grafting (CABG) is associated with activation of leucocytes, the complement cascade and cytokine secretion. Dendritic cells (DC) and monocytes are immunoregulatory cells that may be impacted by CABG contributing to an altered immune status. This study investigated changes in the DC and monocyte immune profile in CABG patients at 5 time-points: admission, peri-operative, ICU, day 3 (D3) and day 5 (D5).

Methods
At each time point, freshly collected whole blood from 50 CABG patients was used in an ex-vivo whole blood culture model. Lipopolysaccharide (LPS) was added in parallel to model an infectious complication. Expression of DC and monocyte co-stimulatory and adhesion molecules and production of intracellular inflammatory mediators was measured via flow cytometry.

Results
CABG resulted in significant perturbation of monocyte and DC responses. DC and monocytes were immunoparalysed as evidenced by failure to respond to LPS stimulation. Modulation of DC and monocyte costimulatory and adhesion molecule expression and inflammatory mediator production was associated with prolonged length of stay in intensive care and post-operative atrial fibrillation. While DC and monocyte expression of co-stimulatory and adhesion molecules recovered towards baseline by D5 post-surgery, their capacity to produce inflammatory mediators did not.

Conclusions
DC and monocyte responses were significantly impaired following CABG. Use of an ex-vivo model to assess immune competency of cardiac surgery patients may provide a tool for the early prediction of adverse outcomes.
Relationship between autoimmunity and lifestyle
Authors: Kimura Koki 
Published: January 2023

Abstract

Introduction
Health promotion is important to prevent functional deterioration of our advanced immune system. The purpose of the present study was to examine the factors associated with the number of times an individual contracts cold and number of days it takes to recover.

Methods
The subjects were 38 healthy females. We used a questionnaire format to survey the dietary patterns and activity levels of the subjects. The dietary patterns were assessed by examining the average meal content consumed per week over the last 1–2 months and meal consumption, including nutritional content and other factors. The activity levels represented the average duration of physical activity per day and exercise duration per week (4 intensity levels: 3≤ metabolic equivalents (METs) &lt;4, 4≤ METs &lt;6, 6≤ METs &lt;8, 8 ≤ METs ≤15).

Results
The mean number of times an individual contracts cold annually was 2.0 ± 1.3 times and number of days it takes to recover was 3.2 ± 1.3 days. The results of the examination of factors associated with the number of times an individual contracts cold annually revealed a significant difference for BMI (r=0.333, P&lt;0.05). In addition, a significant correlation was observed between the number of days it takes to recover from the cold and cholesterol intake (r=0.393, P&lt;0.05). The coping mechanisms used when contracting cold were as follows: going to the hospital (32%); taking over-the-counter medicine (42%); waiting for natural recovery (26%).

Conclusions
This study showed that there was a significant correlation between number of times an individual contracts cold and BMI. In addition, a significant correlation was observed between the number of days it takes to recover from the cold and cholesterol intake.
Differential activation of an innate immune signaling pathway in lymphocytes from patients with multiple sclerosis
Authors: Carrithers Michael D 
Published: January 2023

Abstract
Prior work demonstrated that epithelial V-like antigen (EVA), a cell surface adhesion molecule, is expressed in lymphocytes and is necessary for the efficacy of anti-alpha4integrin treatment of experimental autoimmune encephalomyelitis (EAE), a mouse model of human multiple sclerosis (MS). EVA deficiency is associated with a severe clinical phenotype of EAE in the presence or absence of treatment. Recent work demonstrates that EVA, which is encoded by the mpzl2 gene, also regulates expression of the anti-viral oligoadenylate synthase genes, Oas1 and Oas2. Here the EVA signaling pathway was assessed in patients with MS and healthy controls from the UIC Neuroimmunology Biobank. The goal of this initiative is to assess individual variation in innate immune responses that are associated with severe phenotypes of multiple sclerosis (MS) in underrepresented racial and ethnic minority groups. In response to treatment with the Tlr7/8 agonist R848, peripheral blood lymphocytes from MS patients demonstrated an increase in mpzl2 expression that was not observed in healthy controls. In addition, racial and ethnic differences were observed in the expression of Oas1and Oas2 genes. It is hypothesized that differential innate immune activation of these transcriptional pathways are novel biomarkers and modifiers of disease severity in MS.
This work was funded by the Evelyn Garcia Research Fund at the University of Illinois College of Medicine, Chicago.
Sexual dimorphism in the physiological response of the Apoe
−/− atherosclerosis model to sleep fragmentation
Authors: Moriarty Alina K , Waseem Tayab , Keeter William Coles , Edemobi Stefan , Pham Michael , Sanford Larry , Wellman Laurie , Galkina Elena 
Published: January 2023

Abstract
Sleep fragmentation (SF) is tightly correlated with the development of chronic low grade inflammatory diseases such as, type 2 diabetes and atherosclerosis; however, the exact relationship between SF and atherogenesis is unknown. Little evidence exists regarding the origin of sex differences in sleep behavior. While the role of gender has been studied in atherosclerosis, the impact of gender in SF-associated atherogenesis is not known. Recently, we have shown that high fat diet (HFD) fed male Apolipoprotein E-deficient (Apoe−/−)mice on SF unexpectedly experienced premature death, with 80% of males not surviving past week 2 of SF, while 80% of females survived past week 8 under the same conditions. To investigate the gender effects, male and female Apoe−/− mice were fed a HFD and SF for 10 days. Following HFD and SF, male mice, but not female Apoe−/− mice had enlarged hearts and lymph nodes, as well as peritoneal bleeding. Further, SF resulted in a significantly higher amount of circulating LPS and alterations in the immune composition of bone marrow (BM), blood, and lymph nodes (LN) in male HFD fed Apoe−/− mice vs SF female Apoe−/− mice. We detected a significant decrease in myeloid cells in the BM and blood, as well as a decrease in the percentage of T and B cells in the LN of HFD fed-SF males’ vs diet matched SF females. Interestingly, when male Apoe−/− mice were administered 17b-estradiol orally, in supplement with HFD feeding and SF, they survived past the 14 day death window. Altogether, SF alters the immune response in male atherosclerotic Apoe−/− mice resulting in early death. Our data suggests that the hormonal landscape in female Apoe−/− mice protects against SF-induced premature death via estrogen-dependent mechanisms.
Cell bound complement activation products alone and in combination with low serum complement C3 or C4 have superior diagnostic performance in systemic lupus erythematosus
Authors: Weinstein Arthur , Wallace Daniel J , Putterman Chaim , Arriens Cristina , Askanase Anca , Kalunian Kenneth C , Collins Christopher E , Saxena Amit , Massarotti Elena M , Alexander Roberta Vezza , Ibarra Claudia , Chatham Winn , Ramsey-Goldman Rosalind , Narain Sonali , Chandra Tarun , Ahearn Joseph , Manzi Susan , Dervieux Thierry 
Published: January 2023

Abstract

BACKGROUND
Cell-bound complement activation products (CB-CAPs) are sensitive and specific diagnostic markers of systemic lupus erythematosus (SLE). We compared the performance of CB-CAPs to low serum complement C3 or C4 in distinguishing SLE from other rheumatic diseases and healthy individuals.

METHODS
Adult subjects (n=1200) were enrolled from multiple academic centers, including SLE (498), healthy individuals (252) and subjects with other rheumatic diseases (450). Erythrocyte bound C4d [EC4d] and B-Lymphocyte bound C4d [BC4d] were quantitated using flow cytometry. Serum C3 and C4 levels were determined using immunoturbidimetry. Measurements included sensitivity, specificity, area under the curve (AUC) of the receiver operating characteristic curve (ROC) and Youden Index, for each marker as well as combinations.

RESULTS
Abnormal CB-CAPs status yielded 62% sensitivity with 88% specificity in distinguishing SLE from the group with other diseases compared to low C3/C4 status − 38% sensitivity, 93% specificity. Youden index was 0.492±0.03 for CB-CAPs compared to 0.313±0.03 for low C3/C4 (p&lt;0.01). AUC was higher with BC4d (0.72) than with EC4d (0.68; p&lt;0.01), low C3 (0.62; p&lt;0.01), low C4 (0.62; p&lt;0.01) and low C3 and/or C4 levels (0.66; p&lt;0.01).
The cumulative complement scoring system yielded higher AUC (0.81). A score with greater than 1 complement abnormality yielded 45% sensitivity and 98% specificity.

CONCLUSION
Our data suggests that CB-CAPs have greater diagnostic performance than low serum complement C3/C4. The combination of these complement abnormalities in a composite complement score is superior in distinguishing SLE from other rheumatic diseases and healthy individuals.
Chronic inflammation associated with obesity exacerbates bone loss in mice
Authors: Fields Travis , Ramanan Meera , Rayalam Srujana , Shashidharamurthy Rangaiah 
Published: January 2023

Abstract
Dysfunctional adipose tissue characterized by abnormal inflammatory cytokine production during obesity, is linked to several metabolic disorders including bone loss. An increase in bone fracture incidence due to increased rates of obesity is becoming a significant new health concern. However, it is still obscure whether obesity accelerates bone loss. Herein, we have investigated the systemic weight gain, cytokine production, bone turnover markers and femur bone micro-architecture in high-fat diet (HFD) fed obese mice. HFD mice exhibited excessive visceral fat accumulation (2.4 fold) in the peritoneal cavity and increased body weight (2.1 fold) compared to regular chow diet (RCD) fed mice. The serum levels of pro-inflammatory cytokine IL-6 was increased approximately 8-fold in HFD mice compared to RCD mice. The serum bone turnover marker, C-terminal telopeptides of collagen (CTx), was almost 2-fold higher in HFD mice compared to RCD mice. Further, radiological studies from micro computed tomography (micro-CT) of femur suggests that HFD mice exhibited considerably reduced bone volume fraction (BV/TV) and cortical thickness compared to RCD mice. These results suggest the chronic inflammation associated with many metabolic disorders such as obesity may accelerate bone loss.
CD40 function in immune development and response: Cell type requirements and cytoplasmic domain function
Authors: Lu Ying , Chiang Jeffrey , Zhang Ray , Alkhaleel Farrah , Hodes Richard J 
Published: January 2023

Abstract
CD40 is a TNFR family member and serves as a costimulatory molecule expressed on multiple antigen presenting cell (APC) lineages. The functional significance of CD40 expression is illustrated by human disease and mouse models of life-threatening immune deficiency. CD40-CD40L deficiency affects multiple aspects of immune development and response. However, cell type-specific requirements for CD40 and requirements for CD40 signaling domains have not been comprehensively analyzed. In this study, we use conditional CD40 knockout mice to study cell type requirements and generated CD40 intracellular domain mutants by CRISPR to determine domain-specific functions. CD40 expression on B cells but not DC is required for CD40 dependent superantigen-specific negative selection and for T-cell dependent class-switched antibody responses. TRAF2/3 binding domains of CD40 are critical for these CD40 functions, while deletion of putative TRAF6 binding domain had minimal effect. In contrast, in vivo priming of cytokine-producing T cells depends on CD40 expression on DC but not B cells and requires both TRAF2/3 and TRAF6 domains. CD40 expression on both B cells and DC is required for maximal autoimmune EAE disease induced by recombinant human MOG (rhMOG), and both TRAF2/3 and TRAF6 domains of CD40 are required for this autoimmune response. Initial results indicate that CD40 on thymic epithelial cells and DC contributes to negative selection of tissue restricted antigen-binding T cells. These results identify different CD40-dependent APC requirements and suggest distinct CD40 signaling pathways for specific immune responses. Analysis of the linkage between cell type-specific CD40 function and intracellular signaling is under study.
Brain-Thymus communication is a novel immunosuppressive feature of neurological insults
Authors: Ayasoufi Katayoun , Pfaller Christian K , Khadka Roman H , Jin Fang , Johnson Aaron J. 
Published: January 2023

Abstract
Systemic immunosuppression following neurological insults including stroke, traumatic brain injury, and glioblastoma mutiforme (GBM) causes mortality and leads to failure of therapies. Exact immunological nature and the underlying mechanisms of this immunosuppression are unknown. Our goal was to define effects of neurological insults given exclusively to the brain on the thymus; a primary immune organ. Specifically, we evaluated the effects on the thymus following physical injury with intracranial PBS injection, intracranial (ic) Theiler’s Murine Encephalomyelitis Virus infection, intracranial injection with lipopolysaccharide, CNS tumors (B16 melanoma and GL261 glioma ic), and seizure induction with intraperitoneal Kainic acid injection. These insults resulted in significant thymic involution that is reversible upon clearance of the neurological insult. The extent of thymic involution correlated with the extent of brain injury. Further analysis of the brain-thymus axis in mice with GL261 gliomas was conducted using RNA-Seq. Principle component analysis of RNA-Seq data revealed unbiased separation of thymi of naïve and glioma harboring mice, suggesting that thymus is directly affected by brain injury. To determine the extent to which thymic involution was caused by a soluble factor, we employed parabiosis. This approach demonstrated a soluble factor is responsible for thymic involution. These findings are the first demonstration that neurological insults ubiquitously contribute to immune suppression. We also provide evidence that thymic involution is mediated by a soluble factor, the identification of which could be critical for ameliorating the effect of neurological injuries on immune suppression.
A role for group 2 innate lymphoid cells in muscular dystrophy
Authors: Kastenschmidt Jenna 
Published: January 2023

Abstract
Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder characterized by progressive myofiber degeneration and chronic inflammation. Asynchronous and continuous bouts of injury dysregulate the immune response to injured myofibers, exacerbating muscle degeneration and impairing regeneration. In contrast, activation of type 2 immunity during acute injury is required for efficient muscle regeneration. Evidence in the literature suggests a similar type 2 immune response is activated in dystrophic muscle, but is dysregulated by competing degenerative inflammatory responses. However, the regulation of type 2 immunity in dystrophic muscle is largely unknown. A recently identified subset of immune cells, group 2 innate lymphoid cells (ILC2), were shown to potently regulate type 2 immunity and promote tissue repair. In this study, we found that muscle ILC2s were increased in number and expressed higher levels of interleukin-5 (IL-5) in mdx mice compared to wildtype controls, indicating that muscle degeneration activates ILC2s. In vivo expansion of ILC2s using IL-2/anti-IL-2 complex (IL-2c) and IL-33 enhanced type 2 cytokine expression in mdx skeletal muscle and increased the cross-sectional area of regenerating myofibers, suggesting that ILC2s enhance muscle regeneration through the upregulation of type 2 cytokines. In addition, loss-and gain-of-function experiments demonstrated that ILC2s promote the skeletal muscle recruitment of eosinophils, an innate immune cell population previously shown to promote muscle regeneration. Collectively our data support a working model in which ILC2s promote skeletal muscle regeneration by enhancing type 2 immunity (i.e. eosinophilia and increased type 2 cytokines).