bluuebunny/crossref_metadata_2025 huggingface dataset:
Reaction of SARS-CoV-2 antibodies with other pathogens, vaccines, and food antigens
Authors: Vojdani Aristo , Vojdani Elroy , Melgar Ashley L. , Redd Joshua
Published: September 2022

It has been shown that SARS-CoV-2 shares homology and cross-reacts with vaccines, other viruses, common bacteria and many human tissues. We were inspired by these findings, firstly, to investigate the reaction of SARS-CoV-2 monoclonal antibody with different pathogens and vaccines, particularly DTaP. Additionally, since our earlier studies have shown immune reactivity by antibodies made against pathogens and autoantigens towards different food antigens, we also studied cross-reaction between SARS-CoV-2 and common foods. For this, we reacted monoclonal and polyclonal antibodies against SARS-CoV-2 spike protein and nucleoprotein with 15 different bacterial and viral antigens and 2 different vaccines, BCG and DTaP, as well as with 180 different food peptides and proteins. The strongest reaction by SARS-CoV-2 antibodies were with DTaP vaccine antigen, E. faecalis, roasted almond, broccoli, soy, cashew, α+β casein and milk, pork, rice endochitinase, pineapple bromelain, and lentil lectin. Because the immune system tends to form immune responses towards the original version of an antigen that it has encountered, this cross-reactivity may have its advantages with regards to immunity against SARS-CoV-2, where the SARS-CoV-2 virus may elicit a “remembered” immune response because of its structural similarity to a pathogen or food antigen to which the immune system was previously exposed. Our findings indicate that cross-reactivity elicited by DTaP vaccines in combination with common herpesviruses, bacteria that are part of our normal flora such as E. faecalis, and foods that we consume on a daily basis should be investigated for possible cross-protection against COVID-19. Additional experiments would be needed to clarify whether or not this cross-protection is due to cross-reactive antibodies or long-term memory T and B cells in the blood.
Immune repertoire and evolutionary trajectory analysis in the development of diabetic nephropathy
Authors: Ye Zheng , Zhang Yidi , Huang Nan , Chen Shen , Wu Xiaodong , Li Ling
Published: September 2022

Diabetic nephropathy (DN) is the leading cause of death and the greatest risk to the lives of people with advanced diabetes. Yet, the molecular mechanisms underlying its development and progression remain unknown. In this research, we studied the primary pathways driving DN using transcriptome sequencing and immune repertoire analysis. Firstly, we found that the diversity and abundance of the immune repertoire in late DN were significantly increased, while there was no significant change in early DN. Furthermore, B cell-mediated antibody responses may be the leading cause of DN progression. By analyzing master regulators, we found the key DN-driving transcription factors. In the late stage of DN, immune cells, fibroblasts, and epithelial cells were abundant, but other stromal cells were few. Early DN kidneys had a higher tissue stemness score than normal and advanced DN kidneys. We showed that DN progression involves proximal tubular metabolic reprogramming and stemness restoration using Monocle3. Through WGCNA, we found that co-expression modules that regulate DN progression and immune repertoire diversity mainly regulate immune-related signaling pathways. In addition, we also found that early DN had apparent activation of immune-related signaling pathways mainly enriched in immune cells. Finally, we found that activation of fibroblasts is typical of early DN. These results provide a research basis for further exploring the molecular biology and cellular mechanisms of the occurrence and development of DN and provide a theoretical basis for the prevention and treatment of DN.
Targeting myeloid villains in the treatment with immune checkpoint inhibitors in gastrointestinal cancer
Authors: Kudo-Saito Chie , Boku Narikazu , Hirano Hidekazu , Shoji Hirokazu
Published: September 2022

Despite the clinical outcomes being extremely limited, blocking immune inhibitory checkpoint pathways has been in the spotlight as a promising strategy for treating gastrointestinal cancer. However, a distinct strategy for the successful treatment is obviously needed in the clinical settings. Myeloid cells, such as neutrophils, macrophages, dendritic cells, and mast cells, are the majority of cellular components in the human immune system, but have received relatively less attention for the practical implementation than T cells and NK cells in cancer therapy because of concentration of the interest in development of the immune checkpoint blocking antibody inhibitors (ICIs). Abnormality of myeloid cells must impact on the entire host, including immune responses, stromagenesis, and cancer cells, leading to refractory cancer. This implies that elimination and reprogramming of the tumor-supportive myeloid villains may be a breakthrough to efficiently induce potent anti-tumor immunity in cancer patients. In this review, we provide an overview of current situation of the IC-blocking therapy of gastrointestinal cancer, including gastric, colorectal, and esophageal cancers. Also, we highlight the possible oncoimmunological components involved in the mechanisms underlying the resistance to the ICI therapy, particularly focusing on myeloid cells, including unique subsets expressing IC molecules. A deeper understanding of the molecular and cellular determinants may facilitate its practical implementation of targeting myeloid villains, and improve the clinical outcomes in the ICI therapy of gastrointestinal cancer.
Targeting the innate repair receptor axis via erythropoietin or pyroglutamate helix B surface peptide attenuates hemolytic-uremic syndrome in mice
Authors: Dennhardt Sophie , Pirschel Wiebke , Wissuwa Bianka , Imhof Diana , Daniel Christoph , Kielstein Jan T. , Hennig-Pauka Isabel , Amann Kerstin , Gunzer Florian , Coldewey Sina M.
Published: September 2022

Hemolytic-uremic syndrome (HUS) can occur as a systemic complication of infections with Shiga toxin (Stx)-producing Escherichia coli and is characterized by microangiopathic hemolytic anemia and acute kidney injury. Hitherto, therapy has been limited to organ-supportive strategies. Erythropoietin (EPO) stimulates erythropoiesis and is approved for the treatment of certain forms of anemia, but not for HUS-associated hemolytic anemia. EPO and its non-hematopoietic analog pyroglutamate helix B surface peptide (pHBSP) have been shown to mediate tissue protection via an innate repair receptor (IRR) that is pharmacologically distinct from the erythropoiesis-mediating receptor (EPO-R). Here, we investigated the changes in endogenous EPO levels in patients with HUS and in piglets and mice subjected to preclinical HUS models. We found that endogenous EPO was elevated in plasma of humans, piglets, and mice with HUS, regardless of species and degree of anemia, suggesting that EPO signaling plays a role in HUS pathology. Therefore, we aimed to examine the therapeutic potential of EPO and pHBSP in mice with Stx-induced HUS. Administration of EPO or pHBSP improved 7-day survival and attenuated renal oxidative stress but did not significantly reduce renal dysfunction and injury in the employed model. pHBSP, but not EPO, attenuated renal nitrosative stress and reduced tubular dedifferentiation. In conclusion, targeting the EPO-R/IRR axis reduced mortality and renal oxidative stress in murine HUS without occurrence of thromboembolic complications or other adverse side effects. We therefore suggest that repurposing EPO for the treatment of patients with hemolytic anemia in HUS should be systematically investigated in future clinical trials.
Altered distribution and function of NK-cell subsets lead to impaired tumor surveillance in JAK2V617F myeloproliferative neoplasms
Authors: Fernandes de Oliveira Costa Amanda , Olops Marani Leticia , Mantello Bianco Thiago , Queiroz Arantes Adriana , Aparecida Lopes Izabela , Antonio Pereira-Martins Diego , Carvalho Palma Leonardo , Santos Scheucher Priscila , Lilian dos Santos Schiavinato Josiane , Sarri Binelli Larissa , Araújo Silva Cleide , Kobayashi Susumu S. , Agostinho Machado-Neto João , Magalhães Rego Eduardo , Samuel Welner Robert , Lobo de Figueiredo-Pontes Lorena
Published: September 2022

In cancer, tumor cells and their neoplastic microenvironment can sculpt the immunogenic phenotype of a developing tumor. In this context, natural killer (NK) cells are subtypes of lymphocytes of the innate immune system recognized for their potential to eliminate neoplastic cells, not only through direct cytolytic activity but also by favoring the development of an adaptive antitumor immune response. Even though the protective effect against leukemia due to NK-cell alloreactivity mediated by the absence of the KIR-ligand has already been shown, and some data on the role of NK cells in myeloproliferative neoplasms (MPN) has been explored, their mechanisms of immune escape have not been fully investigated. It is still unclear whether NK cells can affect the biology of BCR-ABL1-negative MPN and which mechanisms are involved in the control of leukemic stem cell expansion. Aiming to investigate the potential contribution of NK cells to the pathogenesis of MPN, we characterized the frequency, receptor expression, maturation profile, and function of NK cells from a conditional Jak2V617F murine transgenic model, which faithfully resembles the main clinical and laboratory characteristics of human polycythemia vera, and MPN patients. Immunophenotypic analysis was performed to characterize NK frequency, their subtypes, and receptor expression in both mutated and wild-type samples. We observed a higher frequency of total NK cells in JAK2V617F mutated MPN and a maturation arrest that resulted in low-numbered mature CD11b+ NK cells and increased immature secretory CD27+ cells in both human and murine mutated samples. In agreement, inhibitory receptors were more expressed in MPN. NK cells from Jak2V617F mice presented a lower potential for proliferation and activation than wild-type NK cells. Colonies generated by murine hematopoietic stem cells (HSC) after mutated or wild-type NK co-culture exposure demonstrated that NK cells from Jak2V617F mice were deficient in regulating differentiation and clonogenic capacity. In conclusion, our findings suggest that NK cells have an immature profile with deficient cytotoxicity that may lead to impaired tumor surveillance in MPN. These data provide a new perspective on the behavior of NK cells in the context of myeloid malignancies and can contribute to the development of new therapeutic strategies, targeting onco-inflammatory pathways that can potentially control transformed HSCs.
Risk Factors and Biomarkers for Immune-Related Adverse Events: A Practical Guide to Identifying High-Risk Patients and Rechallenging Immune Checkpoint Inhibitors
Authors: Chennamadhavuni Adithya , Abushahin Laith , Jin Ning , Presley Carolyn J. , Manne Ashish
Published: September 2022

Immune-related adverse events (irAEs) are a range of complications associated with the use of immune-checkpoint inhibitors (ICIs). Two major classes of ICIs widely used are Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed Cell death-1 (PD-1)/Programmed death-ligand 1 (PD-L1) inhibitors. High-grade irAEs are life-threatening and often cause a severe decline in performance status in such that patients do not qualify for any further anticancer treatments. It is difficult to generalize the evidence in the current literature on risk factors or biomarkers for the entire class of ICIs as the studies so far are either disease-specific (e.g., lung cancer or melanoma) or ICI agent-specific (e.g., pembrolizumab, ipilimumab) or irAE-specific (e.g., pneumonitis or gastritis). In this review, risk factors and biomarkers to consider before initiating or monitoring ICI are listed with a practical purpose in day-to-day practice. Risk factors are grouped into demographics and social history, medical history, and medication history, tumor-specific and agent-specific risk factors. A higher risk of irAE is associated with age <60 years, high body mass index, women on CTLA4 and men on PD-1/PD-L1 agents, and chronic smokers. Patients with significant kidney (Stage IV-V), cardiac (heart failure, coronary artery disease, myocardial infarction, hypertension), and lung (asthma, pulmonary fibrosis, and chronic obstructive pulmonary disease) are at a higher risk of respective organ-specific irAEs. Pre-existing autoimmune disease and chronic use of certain drugs (proton pump inhibitors, diuretics, anti-inflammatory drugs) also increase the irAE-risk. Biomarkers are categorized into circulating blood counts, cytokines, autoantibodies, HLA genotypes, microRNA, gene expression profiling, and serum proteins. The blood counts and certain protein markers (albumin and thyroid-stimulating hormone) are readily accessible in current practice. High neutrophil-lymphocyte ratio, eosinophil/monocyte/lymphocyte counts; TSH and troponins at diagnosis and drop in the white count and lymphocyte count can predict irAE. Other biomarkers with limited evidence are cytokines, autoantibodies, HLA genotypes, microRNA, and gene expression profiling. With fast-expanding approvals for ICIs in various cancer types, knowledge on risk factors and biomarkers can help providers assess the irAE-risk of their patients. Prospective disease and agent-specific studies are needed to provide further insight on this essential aspect of ICI therapy.
Development of a Novel Immune-Related Gene Prognostic Index for Breast Cancer
Authors: Yao Yan , Kong Xinru , Liu Ruijuan , Xu Fei , Liu Gongxi , Sun Changgang
Published: September 2022

Objective

To construct an immune-related gene prognostic index (IRGPI) for breast cancer (BC) and investigate its prognostic specificity and the molecular and immune characteristics.

Methods

BC hub genes were identified from The Cancer Genome Atlas and immune-related databases using weighted gene co-expression network analysis (WGCNA). IRGPI was constructed using univariate, LASSO, and multivariate regression analyses, and was validated with GSE58812 and GSE97342 in the Gene Expression Omnibus database (GEO). At the same time, we evaluated the predictive ability of IRGPI for different BC subtypes. Subsequently, the molecular and immune characteristics, clinical relevance, and benefits of immune checkpoint inhibitor treatment were analyzed for different IRGPI subgroups.

Results

IRGPI consisted of six genes: SOCS3, TCF7L2, TSLP NPR3, ANO6, and HMGB3. The IRGPI 1-, 5-, and 10-years area under curve (AUC) values were 0.635, 0.752, and 0.753, respectively, indicating that IRGPI has good potential in predicting the long-term survival of BC patients, consistent with the results in the GEO cohort. IRGPI showed good predictive power in four different breast cancer subtypes: ER positive, PR positive, HER2 positive and triple-negative (P<0.01). Compared with the low-IRGPI group, the high-IRGPI group had a worse prognosis and a lower degree of immune infiltrating cells (p < 0.05). IRGPI showed specificity in distinguishing age, TNM stage, ER, and HER2 statuses, and our study found that the high-IRGPI group had low tumor immune dysfunction and exclusion (TIDE), microsatellite instability (MSI), and T cell dysfunction scores (p < 0.05). In addition, compared with the TIDE and TIS models, showed that the AUCs of IRGPI were better during the 5-year follow-up.

Conclusion

IRGPI can be used as an independent prognostic indicator of breast cancer, providing a method for monitoring the long-term treatment of BC.
Coexistence of multiple anti-neuronal antibodies in autoimmune encephalitis in China: A multi-center study
Authors: Qiao Shan , Zhang Shan-Chao , Wang Zhi-Hao , Wang Lei , Zhang Ran-Ran , Li Hai-Yun , Jin Yang , Liu Ling-Ling , Wang Mei-Ling , Wang Ai-Hua , Liu Xue-Wu
Published: September 2022

Background

Given that the combination of multiple antibodies in autoimmune encephalitis (AE) is rare and its clinical significance is unclear, this study aimed to investigate the clinical characteristics and significance of overlapping multiple anti-neuronal antibodies in patients with AE.

Methods

We conducted a retrospective analysis of the clinical characteristics, treatment, and prognostic details of 22 patients with multiple coexisting antibodies from multiple clinical centers in China.

Results

Among the 276 patients who were AE antibody-positive, 22 (7.97%) had two or more antibodies. Among the 22 patients with coexisting AE-related antibodies, 14 patients (63.63%) were combined of cell surface and intracellular antibody, and the remaining 8 patients (36.36%) were detected to be cell surface antibody positive only. The main symptoms of the 22 patients in this cohort included fever, seizures, memory impairment, cognitive decline, and sleep disorders. Five (22.73%) patients had tumors, among whom four had small-cell lung cancers, and one had mediastinal tumors. A total of 20 patients were treated with steroids and intravenous immunoglobulin, and 18 showed varying degrees of symptomatic improvement after first-line immunotherapy. Three patients died of tumor progression or chemotherapy complications.

Conclusion

The coexistence of multiple anti-neuronal antibodies in patients with AE may cause a superimposition and diversification of clinical manifestations. Combined paraneoplastic antibody positivity may be suggestive of an underlying malignancy.
Maternal siRNA silencing of placental SAA2 mitigates preterm birth following intrauterine inflammation
Authors: Liu Yang , Liu Jin , Liu Anguo , Yin Hillary , Burd Irina , Lei Jun
Published: September 2022

The placental inflammatory processes induced maternally result in preterm birth (PTB). Serum amyloid A (SAA) is a well-known biomarker of inflammation. The objective of this study was to investigate whether murine placental SAA isoforms (SAA1–4) participate in the mechanism of spontaneous PTB and whether maternal regulation of SAA production may serve as a therapeutic approach. During the gestation, all isoforms of SAA were detectable except SAA2. The mouse model of intrauterine inflammation was established using LPS infusion to the uterus. Following intrauterine inflammation, placental SAA2 increased significantly. Inhibition ofSaa2, using siSaa2, markedly decreased PTB. The increased placental expression of pro-inflammatory cytokinesIl1β,Il6, andTnfαwere downregulated by siSaa2treatment. Maternal inhibition ofSaa2did not change the expression ofSaa1–4in the fetal brain. Explant inflammatory culture of placentas with siSaa2showed similar results to ourin vivoexperiments. This study demonstrates the highly expressed placental SAA2 as a novel therapeutic target, and maternal administration of siRNA as a promising approach to alleviate PTB.
Cuproptosis-related modification patterns depict the tumor microenvironment, precision immunotherapy, and prognosis of kidney renal clear cell carcinoma
Authors: Cai Zhiyong , He You'e , Yu Zhengzheng , Hu Jiao , Xiao Zicheng , Zu Xiongbing , Li Zhenghao , Li Huihuang
Published: September 2022

Background

Due to the different infiltration abundance of immune cells in tumor, the efficacy of immunotherapy varies widely among individuals. Recently, growing evidence suggested that cuproptosis has impact on cancer immunity profoundly. However, the comprehensive roles of cuproptosis-related genes in tumor microenvironment (TME) and in response to immunotherapy are still unclear.

Methods

Based on 43 cuproptosis-related genes, we employed unsupervised clustering to identify cuproptosis-related patterns and single-sample gene set enrichment analysis algorithm to build a cuproptosis signature for individual patient’s immune cell infiltration and efficacy of immune checkpoint blockade (ICB) evaluation. Then, the cuproptosis-related genes were narrowed down using univariate Cox regression model and least absolute shrinkage and selection operator algorithm. Finally, a cuproptosis risk score was built by random survival forest based on these narrowed-down genes.

Results

Two distinct cuproptosis-related patterns were developed, with cuproptosis cluster 1 showing better prognosis and higher enrichment of immune-related pathways and infiltration of immune cells. For individual evaluation, the cuproptosis signature that we built could be used not only for predicting immune cell infiltration in TME but also for evaluating an individual’s sensitivity to ICBs. Patients with higher cuproptosis signature scores exhibited more activated cancer immune processes, higher immune cell infiltration, and better curative efficacy of ICBs. Furthermore, a robust cuproptosis risk score indicated that patients with higher risk scores showed worse survival outcomes, which could be validated in internal and external validation cohorts. Ultimately, a nomogram which combined the risk score with the prognostic clinical factors was developed, and it showed excellent prediction accuracy for survival outcomes.

Conclusion

Distinct cuproptosis-related patterns have significant differences on prognosis and immune cell infiltration in kidney renal clear cell carcinoma (KIRC). Cuproptosis signature and risk score are able to provide guidance for precision therapy and accurate prognosis prediction for patients with KIRC.
Desmoglein compensation hypothesis fidelity assessment in Pemphigus
Authors: Sielski Lauren , Baker John , DePasquale Michael C. , Attwood Kristopher , Seiffert-Sinha Kristina , Sinha Animesh A.
Published: September 2022

The pemphigus group of autoimmune blistering diseases encompasses pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Lesion location in pemphigus has been elegantly postulated by the Desmoglein Compensation Hypothesis (DCH), which references the distribution of desmoglein (Dsg) proteins in the epidermis along with a patient’s autoantibody profile to describe three different lesion phenotypes: PF is characterized by subcorneal lesions in the presence of anti-Dsg1 antibodies only, while lesions in PV are suprabasilar and accompanied by anti-Dsg3 antibodies only in mucosal PV, or both anti-Dsg3 and anti-Dsg1 in the case of mucocutaneous PV. While the validity of this hypothesis has been supported by several studies and is prominently featured in textbooks of dermatology, a number of logical inconsistencies have been noted and exceptions have been published in several small-scale studies. We sought to comprehensively assess the extent to which patient clinical and autoantibody profiles contradict the DCH, and characterize these contradictions in a large sample size of 266 pemphigus patients. Remarkably, we find that roughly half of active PV and PF patients surveyed present with a combination of lesion morphology and anti-Dsg3/1 levels that contradict the DCH, including: patients with a cutaneous only PV presentation, mucocutaneous disease in the absence of either Dsg3, Dsg1, or both, and mucosal disease in the absence of Dsg3 or presence of Dsg1. We also find stark differences in fidelity to the DCH based on ethnicity and HLA-association, with the lowest proportion of adherence in previously understudied populations. These findings underscore the need to expand our understanding of pemphigus morphology beyond the DCH, in particular for populations that have not been a focus in previous investigation.
A novel T-cell proliferation-associated regulator signature pre-operatively predicted the prognostic of bladder cancer
Authors: Hou Jian , Wen Xiangyang , Lu Zhenquan , Wu Guoqing , Yang Guang , Tang Cheng , Qu Genyi , Xu Yong
Published: September 2022

Background

Bladder cancer (BCa) is a remarkably malignant and heterogeneous neoplastic disease, and its prognosis prediction is still challenging. Even with the mounting researches on the mechanisms of tumor immunotherapy, the prognostic value of T-cell proliferation regulators in bladder cancer remains elusive.

Methods

Herein, we collected mRNA expression profiles and relevant clinical information of bladder cancer sufferers from a publicly available data base. Then, the LASSO Cox regression model was utilized to establish a multi-gene signature for the TCGA cohort to predict the prognosis and staging of bladder cancer. Eventually, the predictive power of the model was validated by randomized grouping.

Results

The outcomes revealed that most genes related to T-cell proliferation in the TCGA cohort exhibited different expressions between BCa cells and neighboring healthy tissues. Univariable Cox regressive analyses showed that four DEGs were related to OS in bladder cancer patients (p<0.05). We constructed a histogram containing four clinical characteristics and separated sufferers into high- and low-risk groups. High-risk sufferers had remarkably lower OS compared with low-risk sufferers (P<0.001). Eventually, the predictive power of the signature was verified by ROC curve analyses, and similar results were obtained in the validation cohort. Functional analyses were also completed, which showed the enrichment of immune-related pathways and different immune status in the two groups. Moreover, by single-cell sequencing, our team verified that CXCL12, a T-lymphocyte proliferation regulator, influenced bladder oncogenesis and progression by depleting T-lymphocyte proliferation in the tumor microenvironment, thus promoting tumor immune evasion.

Conclusion

This study establishes a novel T cell proliferation-associated regulator signature which can be used for the prognostic prediction of bladder cancer. The outcomes herein facilitate the studies on T-cell proliferation and its immune micro-environment to ameliorate prognoses and immunotherapeutic responses.
T-cell exhaustion in immune-mediated inflammatory diseases: New implications for immunotherapy
Authors: Gao Zhanyan , Feng Yang , Xu Jinhua , Liang Jun
Published: September 2022

Immune-mediated inflammatory diseases(IMIDs) are referred to as highly disabling chronic diseases affecting different organs and systems. Inappropriate or excessive immune responses with chronic inflammation are typical manifestations. Usually in patients with chronic infection and cancer, due to long-term exposure to persistent antigens and inflammation microenvironment, T-cells are continuously stimulated and gradually differentiate into an exhausted state. Exhausted T-cells gradually lose effector function and characteristics of memory T-cells. However, existing studies have found that exhausted T-cells are not only present in the infection and tumor environment, but also in autoimmunity, and are associated with better prognosis of IMIDs. This suggests new prospects for the application of this reversible process of T-cell exhaustion in the treatment of IMID. This review will focus on the research progress of T-cell exhaustion in several IMIDs and its potential application for diagnosis and treatment in IMIDs.
(NZW × BXSB) F1 male mice: An unusual, severe and fatal mouse model of lupus erythematosus
Authors: Almizraq Ruqayyah J. , Frias Boligan Kayluz , Loriamini Melika , McKerlie Colin , Branch Donald R.
Published: September 2022

Background

Systemic lupus erythematosus (SLE) is a chronic autoimmune/inflammatory disease. The heterogeneity and complexity of clinical presentation has made it challenging to study or treat this syndrome. The (NZW×BXSB) F1 lupus-prone male mouse model of this disease is potentially useful to study mechanism and treatment modalities, but there is a lack of information about this model’s characterization and disease progression. Therefore, the aim was to examine this lupus model’s physical/clinical disease presentation and its immunological status.

Materials and methods

Clinical and physical status were observed in 8- and 16-week-old male and female (± 1 week) (NZW/LacJ x BXSB/MpJ) F1 mice (n = 8 per group). Young males (8 ± 1 week) without disease and female (16 ± 1 week) mice served as controls. Physical changes, quantitative values of autoantibodies, and blood cell parameters were determined. Necropsy and post-mortem histopathology were also performed.

Results

With aging (≥ 12 weeks), significant increases in severe abdominal distension/swelling, inability to walk, paleness of paws and significant weight increase were observed compared to controls (p < 0.05). The necropsy examination showed abdominal distension associated with serous effusion and histological examination identified severe edema and multi-organ abnormalities (spleen, lymph nodes, and kidney). Significant increases in anti-double-stranded DNA antibody (anti-dsDNA) was seen in old/sick compared to female (p = 0.0002) or young male (p = 0.0036) mice. Old mice developed immune thrombocytopenia compared to female (p = 0.0056) and young male (p = 0.0007) mice. Anti-platelet was detectable in old, sick mice. The mortality rate increased with aging; more than 35% of male mice died during this study between the ages of 13-18 weeks.

Conclusion

We found that the (NZW/LacJ x BXSB/MpJ) F1 male mice spontaneously exhibit, over varying lengths of time, extremely severe and fatal clinical disease symptoms. This model may be too severe to be helpful in investigating SLE and testing potential treatment modalities.
Real-world effectiveness and protection of SARS-CoV-2 vaccine among patients hospitalized for COVID-19 in Xi’an, China, December 8, 2021, to January 20, 2022: A retrospective study
Authors: Li Xiaowei , Xu Yinjuan , Li Xiaomeng , Liu Wenbin , Yao Dan , Chen Weichao , Yu Hongchuan , He Langchong , Lu Shemin , Jiang Congshan , Zhu Wenhua , Meng Liesu
Published: September 2022

Introduction

In December 2021, a large-scale epidemic broke out in Xi’an, China, due to SARS-CoV-2 infection. This study reports the effect of vaccination on COVID-19 and evaluates the impact of different vaccine doses on routine laboratory markers.

Methods

The laboratory data upon admission, of 231 cases with COVID-19 hospitalized from December 8, 2021 to January 20, 2022 in Xi’an, including blood routine, lymphocyte subtypes, coagulative function tests, virus specific antibodies and blood biochemical tests were collected and analyzed.

Results

Of the 231 patients, 21 were not vaccinated, 158 were vaccinated with two doses and 52 with three doses. Unvaccinated patients had a higher proportion of moderate and severe symptoms than vaccinated patients, while two-dose vaccinated patients had a higher proportion than three-dose vaccinated patients. SARS-CoV-2 specific IgG levels were significantly elevated in vaccinated patients compared with unvaccinated patients. Particularly, unvaccinated patients had lower counts and percentages of lymphocytes, eosinophils and CD8+ T-lymphocytes, and elevated coagulation-related markers. In addition, vaccination had no effect on liver and kidney function.

Conclusions

Vaccination against SARS-CoV-2, inducing high IgG level and increased CD8+ T cells and eosinophils, and regulating coagulation function, can significantly attenuate symptoms of COVID-19, suggesting that the vaccine remains protective against SARS-CoV-2.
Eosinophilic gastrointestinal disorders in patients with inborn errors of immunity: Data from the USIDNET registry
Authors: Tran Paulina , Gober Laura , Garabedian Elizabeth K. , Fuleihan Ramsay L. , Puck Jennifer M. , Sullivan Kathleen E. , Spergel Jonathan M. , Ruffner Melanie A.
Published: September 2022

Rationale

Eosinophilic gastrointestinal disorders (EGID), including eosinophilic esophagitis (EoE), are inflammatory disorders of the gastrointestinal mucosa mediated by complex immune mechanisms. Although there have been initial reports of EGID in patients with inborn errors of immunity (IEI), little is known about the presentation of EGID in immunodeficient individuals.

Methods

We queried the U.S. Immunodeficiency Network (USIDNET) for patient records including the terms eosinophilic esophagitis, gastritis, enteritis, or colitis. We analyzed 74 patient records from the database, including diagnoses, demographics, infectious history, laboratory findings, genetic studies, therapeutic interventions, and clinical outcomes.

Results

We examined 74 patient records. A total of 61 patients had isolated EoE, and 13 had distal gastrointestinal involvement consistent with EGID. The most common IEI were common variable immunodeficiency (43.2%), some form of combined immunodeficiency (21.6%), chronic granulomatous disease (8.1%), hyper-IgE syndrome (6.8%), and autoimmune lymphoproliferative syndrome (6.8%). The median age at presentation with IEI was 0.5 years (IQR 1.725, max 39 years) and 56.76% were male. Approximately 20% of the patients in the cohort received a hematopoietic stem cell transplantation for treatment of IEI, but the timing of the HSCT in relationship to the EGID diagnosis was unknown.

Conclusions

Here, we report EGID in a diverse cohort of IEI patients, suggesting that both non-EoE EGID and EoE can be seen as comorbid conditions with a variety of IEI. Our data suggests that EGID may be more common in patients with IEI than would be expected based on estimates of EGID in the general population.
Bioinformatics and systems-biology analysis to determine the effects of Coronavirus disease 2019 on patients with allergic asthma
Authors: Fang Hongwei , Sun Zhun , Chen Zhouyi , Chen Anning , Sun Donglin , Kong Yan , Fang Hao , Qian Guojun
Published: September 2022

Background

The coronavirus disease (COVID-19) pandemic has posed a significant challenge for global health systems. Increasing evidence shows that asthma phenotypes and comorbidities are major risk factors for COVID-19 symptom severity. However, the molecular mechanisms underlying the association between COVID-19 and asthma are poorly understood. Therefore, we conducted bioinformatics and systems biology analysis to identify common pathways and molecular biomarkers in patients with COVID-19 and asthma, as well as potential molecular mechanisms and candidate drugs for treating patients with both COVID-19 and asthma.

Methods

Two sets of differentially expressed genes (DEGs) from the GSE171110 and GSE143192 datasets were intersected to identify common hub genes, shared pathways, and candidate drugs. In addition, murine models were utilized to explore the expression levels and associations of the hub genes in asthma and lung inflammation/injury.

Results

We discovered 157 common DEGs between the asthma and COVID-19 datasets. A protein–protein-interaction network was built using various combinatorial statistical approaches and bioinformatics tools, which revealed several hub genes and critical modules. Six of the hub genes were markedly elevated in murine asthmatic lungs and were positively associated with IL-5, IL-13 and MUC5AC, which are the key mediators of allergic asthma. Gene Ontology and pathway analysis revealed common associations between asthma and COVID-19 progression. Finally, we identified transcription factor–gene interactions, DEG–microRNA coregulatory networks, and potential drug and chemical-compound interactions using the hub genes.

Conclusion

We identified the top 15 hub genes that can be used as novel biomarkers of COVID-19 and asthma and discovered several promising candidate drugs that might be helpful for treating patients with COVID-19 and asthma.
The yin-yang of immunity: Immune dysregulation in myelodysplastic syndrome with different risk stratification
Authors: Peng Xiaohuan , Zhu Xiaofeng , Di Tianning , Tang Futian , Guo Xiaojia , Liu Yang , Bai Jun , Li Yanhong , Li Lijuan , Zhang Liansheng
Published: September 2022

Myelodysplastic syndrome (MDS) is a heterogeneous group of myeloid clonal diseases with diverse clinical courses, and immune dysregulation plays an important role in the pathogenesis of MDS. However, immune dysregulation is complex and heterogeneous in the development of MDS. Lower-risk MDS (LR-MDS) is mainly characterized by immune hyperfunction and increased apoptosis, and the immunosuppressive therapy shows a good response. Instead, higher-risk MDS (HR-MDS) is characterized by immune suppression and immune escape, and the immune activation therapy may improve the survival of HR-MDS. Furthermore, the immune dysregulation of some MDS changes dynamically which is characterized by the coexistence and mutual transformation of immune hyperfunction and immune suppression. Taken together, the authors think that the immune dysregulation in MDS with different risk stratification can be summarized by an advanced philosophical thought “Yin-Yang theory” in ancient China, meaning that the opposing forces may actually be interdependent and interconvertible. Clarifying the mechanism of immune dysregulation in MDS with different risk stratification can provide the new basis for diagnosis and clinical treatment. This review focuses on the manifestations and roles of immune dysregulation in the different risk MDS, and summarizes the latest progress of immunotherapy in MDS.
IgE receptor responsiveness of basophils in chronic inducible urticaria
Authors: Mizuno Mayuko , Oda Yoshiko , Imamura Shinya , Washio Ken , Fukumoto Takeshi , Fukunaga Atsushi
Published: September 2022

Introduction

Chronic inducible urticaria (CIndU) is a subgroup of chronic urticaria induced by a specific stimulus. We evaluated basophil characteristics in patients with CIndU and compared with those in patients with chronic spontaneous urticaria (CSU) and healthy controls (HCs).

Methods

Blood was collected from patients, and a basophil activation test (BAT) was performed. Basophil responsiveness and surface marker expression in patients with CIndU were compared with those in patients with CSU and HCs. For some patients with CIndU, blood was collected before and after wheals were induced. In these cases, we compared the responsiveness of basophils before and after the appearance of wheals.

Result

HCs (n=23) and patients with CIndU (n=24) or CSU (n=38) were enrolled in the study. The degree of basophil activation at steady state in patients with CIndU was higher than in HCs. Basophil responsiveness via high-affinity IgE receptor (FcϵRI) stimulation with anti-IgE or anti-FcϵRI antibody in patients with CIndU was equivalent to that in HCs, and higher than that in patients with CSU. No abnormalities in IgE and FcϵRI expressions on the surface of basophils in patients with CIndU were observed. When we induced wheals in some patients with CIndU and performed a BAT before and after the appearance of wheals, no significant changes were found.

Conclusion

Peripheral blood basophils in CIndU were slightly activated at steady state, but no abnormalities in basophil responsiveness. In future, a higher number of cases should be enrolled to confirm the role of basophils and refine therapeutic targets for CIndU.
Nonalcoholic fatty liver disease in inflammatory arthritis: Relationship with cardiovascular risk
Authors: Barbarroja Nuria , Ruiz-Ponce Miriam , Cuesta-López Laura , Pérez-Sánchez Carlos , López-Pedrera Chary , Arias-de la Rosa Iván , Collantes-Estévez Eduardo
Published: September 2022

Liver disease is one of the most important causes of morbidity and mortality worldwide whose prevalence is dramatically increasing. The first sign of hepatic damage is inflammation which could be accompanied by the accumulation of fat called non-alcoholic fatty liver disease (NAFLD), causing damage in the hepatocytes. This stage can progress to fibrosis where the accumulation of fibrotic tissue replaces healthy tissue reducing liver function. The next stage is cirrhosis, a late phase of fibrosis where a high percentage of liver tissue has been replaced by fibrotic tissue and liver functionality is substantially impaired. There is a close interplay of cardiovascular disease (CVD) and hepatic alterations, where different mechanisms mediating this relation between the liver and systemic vasculature have been described. In chronic inflammatory diseases such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA), in which the CVD risk is high, hepatic alterations seem to be more prevalent compared to the general population and other rheumatic disorders. The pathogenic mechanisms involved in the development of this comorbidity are still unraveled, although chronic inflammation, autoimmunity, treatments, and metabolic deregulation seem to have an important role. In this review, we will discuss the involvement of liver disease in the cardiovascular risk associated with inflammatory arthritis, the pathogenic mechanisms, and the recognized factors involved. Likewise, monitoring of the liver disease risk in routine clinical practice through both, classical and novel techniques and indexes will be exposed. Finally, we will examine the latest controversies that have been raised about the effects of the current therapies used to control the inflammation in RA and PsA, in the liver damage of those patients, such as methotrexate, leflunomide or biologics.
Molecular cloning, characterization, and expression of two 5-HTRs from the pearl oyster Pinctada fucata martensii
Authors: Zhu Shaojie , He Yubo , Xu Qiongyu , Zhang Jiabin , Yang Chuangye , Hao Ruijuan , Li Junhui , Deng Yuewen
Published: September 2022

The receptors of serotonin, also known as 5-hydroxytryptamine receptor (5-HTR) can mediate regulatory metamorphosis processes in a variety of mollusks. Studying the mechanisms of metamorphosis of the pearl oyster is significant to elucidate breeding, resource recovery and marine pearl production. In this study, two 5-HTR genes from Pinctada fucata martensii (Pm5-HTR2 and Pm5-HTR4) were cloned. A total of 1623 bp open reading frame was identified in Pm5-HTR2, and a 1185 bp open reading frame was detected in Pm5-HTR4; these open reading frames encoded a 540-residue polypeptide and a 394-residue polypeptide, respectively. We also conducted a domain analysis, which indicated that Pm5-HTR2 and Pm5-HTR4 contained a seven-transmembrane domain and revealed that the receptors had high similarity to Crassostrea gigas 5-HTR2 (54.62%) and 5-HTR4 (66.23%). Sequence analysis demonstrated conserved advanced structure and motifs (the DRY/ERY and NPXXY motifs). The expression pattern analysis revealed high expression levels of Pm5-HTR2 and Pm5-HTR4 during the developmental stages. ISH analysis showed that Pm5-HTR2 was primarily expressed in the FE, B, T, EU, and EL stages and Pm5-HTR4 was mainly expressed in the FE, B, T, D, EU, and EL stages. These results suggest that 5-HTRs may play key roles in P. f. martensii larval metamorphosis.
Temporal and spatial variation of petroleum hydrocarbons and microbial communities during static release of oil pollution sediments
Authors: Li Haoshuai , Sun Hu , Wang Xinping , Li Fujuan , Cao Lixin , Li Yang , Dong Ranran , Sun Yuxiang , Sun Peiyan , Bao Mutai
Published: September 2022

The migration and transformation of the petroleum hydrocarbons from sediments into water columns is an important basis for assessing the impact on marine environment. In this paper, a static release experiment of crude oils from the Bohai Sea was carried out to evaluate the temporal and spatial variation of petroleum hydrocarbons and microbial communities. The results showed C1 phenanthrene (C1-P) can be used as an evaluation index of different crude oils during static release of oil pollution sediments and their trends of the static release were similar. The crude oil with higher C1-P content released C1-P into the water body significantly higher. After 72 hours, the C1-P release degree of crude oil with a smaller viscosity was more obvious. In the crude oil with the smallest viscosity and the higher viscosity, the bacterial phyla abundance increase was greater. And more importantly, the top 10 abundance of the microbial communities in the water columns and sediments appeared partial (3 species) replacement phenomenon. The research results can deep understanding the migration and transformation of the petroleum hydrocarbons from oil pollution sediments and understanding of the interaction between extreme weather events and human activities by incorporating an eco-evolutionary perspective.
Seasonal changes in beach resilience along an urbanized barrier island
Authors: Mendoza Ernesto Tonatiuh , Torres-Freyermuth Alec , Ojeda Elena , Medellín Gabriela , Rioja-Nieto Rodolfo , Salles Paulo , Turki Imen
Published: September 2022

Beach width, dune height, and vegetation coverage are key parameters to assess beach resistance and resilience to storms. However, coastal development often causes beach ecosystem degradation due to poor coastal management. We propose a Coastal Resilience Index from Remote Sensors (CRIfRS) for urbanized coasts based on aerial photogrammetry. The study area, located along a 7.8 km stretch of coast on a barrier island, is characterized by persistent alongshore sediment transport and the presence of coastal structures and beach-front houses. Contrary to previous studies, we focus on anthropogenic perturbations (coastal urbanization and coastal structures), instead of hydrodynamic conditions (storms), since erosion in this region is mainly associated with alongshore sediment transport gradients induced by coastal structures. Thus, the CRIfRS is based on the relation of three indicators that affect the beach functionality for coastal protection: beach width, coastal structure influence area, and vegetation coverage. The CRIfRS was divided into five categories: Very Low resilience (VL), Low resilience (L), Medium resilience (M), High resilience (H), and Very High resilience (VH). The CRIfRS presented an important spatial and temporal variability due to changing environmental conditions and the deployment of new coastal structures. For the study period, the percentage of the coast within the VL and L resilience classification increased, whereas the percentage of the coast classified as M, H, and VH resilience decreased. During the winter storm season, the resilience increased mainly due to the cross-shore transport whilst during mean wave conditions (i.e., sea-breeze conditions) the long-shore transport becomes more persistent and thus the coastal structures play an important role interrupting the sediment flux. Additionally, the CRIfRS trajectory shows an overall increase of the L resilience and an overall decrease of the H resilience values. This study highlights the important role of anthropogenic perturbations on the assessment of coastal resilience for highly urbanized coasts. The CRIfRS can help to improve the coastal management by assessing the coastal protection capability of beaches considering both natural and anthropogenic factors.