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Antagonist anti-LIF antibody derived from naive human scFv phage library inhibited tumor growth in mice

Leukemia inhibitory factor (LIF) is a multifunctional member of the IL-6 cytokine family that activates downstream signaling pathways by binding to the heterodimer consisting of LIFR and gp130 on the cell surf...

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Pre-treatment plasma retinol binding protein 4 level and its change after treatments predict systemic treatment response in psoriasis patients

Retinol binding protein 4 (RBP4) is a mediator of inflammation and related to skin lesion formation, which suggests its engagement in psoriasis pathology and progression. This study intended to explore the cha...

KIR2DL1 gene is a surrogate marker of protection against infection-related hospitalization among HIV-1 unexposed versus exposed uninfected infants in Cameroon

HIV-exposed uninfected infants (HEU) appear more vulnerable to infections compared to their HIV-unexposed uninfected (HUU) peers, generally attributed to poor passive immunity acquired from the mother. This ma...

Transcriptomics explores potential mechanisms for the development of Primary Sjogren’s syndrome to diffuse large B-cell lymphoma in B cells

Primary Sjogren's syndrome (pSS) is a prevalent autoimmune disease. The immune dysregulation it causes often leads to the development of diffuse large B-cell lymphoma (DLBCL) in clinical practice. However, how...

Serum immunoglobulin concentrations and risk of type 2 diabetes mellitus in adults: a prospective cohort study from the TCLSIH study

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia resulting from defects in insulin secretion and/or insulin action. Increasing evidence suggests that inflammation played a...

Histone acetylation risk model predicts prognosis and guides therapy selection in glioblastoma: implications for chemotherapy and anti-CTLA-4 immunotherapy

Glioblastoma is characterized by high aggressiveness, frequent recurrence, and poor prognosis. Histone acetylation-associated genes have been implicated in its occurrence and development, yet their predictive ...

Immunological factors, important players in the development of asthma

Asthma is a heterogeneous disease, and its development is the result of a combination of factors, including genetic factors, environmental factors, immune dysfunction and other factors. Its specific mechanism ...

Multiplex array analysis of circulating cytokines and chemokines in COVID-19 patients during the first wave of the SARS-CoV-2 pandemic in Milan, Italy

The systemic inflammatory syndrome called “cytokine storm” has been described in COVID-19 pathogenesis, contributing to disease severity. The analysis of cytokine and chemokine levels in the blood of 21 SARS-C...

TLR7 agonist, DSP-0509, with radiation combination therapy enhances anti-tumor activity and modulates T cell dependent immune activation

TLR7 is a key player in the antiviral immunity. TLR7 signaling activates antigen-presenting cells including DCs and macrophages. This activation results in the adaptive immunity including T cells and B cells. ...

The role of immune-inflammatory markers in children with complicated and uncomplicated malaria in Enugu, Nigeria

There is currently insufficient data regarding immune parameters and relationship with severity of malaria infection in Enugu, Nigeria where the economic and social costs of the disease and its management are ...

Putative new combination vaccine candidates identified by reverse vaccinology and genomic approaches to control enteric pathogens

The pathogenic microorganisms that cause intestinal diseases can significantly jeopardize people's health. Currently, there are no authorized treatments or vaccinations available to combat the germs responsibl...

Interstitial lung diseases (ILD) in common variable immunodeficiency (CVID) patients: a study from Iran

Interstitial lung disease (ILD) is a prevalent complication in patients with common variable immunodeficiency (CVID) and is often related to other characteristics such as bronchiectasis and autoimmunity. Becau...

Evaluation of immunophenotypic alterations of peripheral blood lymphocytes and their sub-sets in uncomplicated P. Falciparum infection

Malaria is a life-threatening parasitic disease typically transmitted through the bite of an infected Anopheles mosquito. There is ample evidence showing the potential of malaria infection to affect the counts...

Neutralizing antibody responses assessment after vaccination in people living with HIV using a surrogate neutralization assay

HIV has been reported to interfere with protective vaccination against multiple pathogens, usually through the decreased effectiveness of the antibody responses. We aimed to assess neutralizing antibody respon...

LCP1 correlates with immune infiltration: a prognostic marker for triple-negative breast cancer

Triple-Negative Breast Cancer (TNBC) is known for its aggressiveness and treatment challenges due to the absence of ER, PR, and HER2 receptors. Our work emphasizes the prognostic value of LCP1 (Lymphocyte cyto...

Gut microbiota regulation of T lymphocyte subsets during systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of pro-inflammatory and anti-inflammatory lymphocytes. Growing evidence shown that gut microbiota participated in the oc...

NLRP3 (rs10754558) gene polymorphism and tumor necrosis factor alpha as predictors for disease activity and response to methotrexate and adalimumab in psoriasis

Psoriasis has a global prevalence of 1–3%, with variations observed across different ethnic groups and geographical areas. Disease susceptibility and response to anti-tumor necrosis factor-α (TNFα) drugs sugge...

Immune-mediated inflammatory diseases and periodontal disease: a bidirectional two-sample mendelian randomization study

Previous observational studies have shown a bidirectional association between immune-mediated inflammatory disorders (IMID) and periodontal disease. However, evidence regarding the causal role of IMID and peri...

The effects of killer cell immunoglobulin-like receptor (KIR) genes on susceptibility to severe COVID-19 in the Iranian population

Variations in the innate and adaptive immune response systems are linked to variations in the severity of COVID-19. Natural killer cell (NK) function is regulated by sophisticated receptor system including Kil...

Systemic treatment options for non-small cell lung cancer after failure of previous immune checkpoint inhibitors: a bayesian network meta-analysis based on randomized controlled trials

Although immune checkpoint inhibitors (ICIs) have brought survival benefits to non-small cell lung cancer (NSCLC), disease progression still occurs, and there is no consensus on the treatment options for these...

Upregulated miR-146b-3p predicted rheumatoid arthritis development and regulated TNF-α-induced excessive proliferation, motility, and inflammation in MH7A cells

Rheumatoid arthritis (RA) is a chronic immune system disease with a high disability rate threatening the living quality of patients. Identifying potential biomarkers for RA is of necessity to improve the preve...

Humoral immune response and safety of Sars-Cov-2 vaccine in people with multiple sclerosis

For the past three years, the pandemic has had a major effect on global public health, mainly on those with underlying medical conditions, such as people living with Multiple Sclerosis. Vaccination among this ...

The immune factors have complex causal regulation effects on kidney stone disease: a mendelian randomization study

Previous studies have reported the potential impact of immune cells on kidney stone disease (KSD), but definitive causal relationships have yet to be established. The purpose of this paper is to elucidate the ...

miR-486-5p predicted adverse outcomes of SCAP and regulated K. pneumonia infection via FOXO1

Severe community-acquired pneumonia (SCAP) is a common respiratory system disease with rapid development and high mortality. Exploring effective biomarkers for early detection and development prediction of SCA...

Identification of four mitochondria-related genes in sepsis based on RNA sequencing technology

The purpose of this study was to identify and analyze the mitochondrial genes associated with sepsis patients in order to elucidate the underlying mechanism of sepsis immunity and provide new ideas for the cli...

Potential role of IGF-1R in the interaction between orbital fibroblasts and B lymphocytes: an implication for B lymphocyte depletion in the active inflammatory phase of thyroid-associated ophthalmopathy

Thyroid eye disease (TED) is an inflammatory process involving lymphocyte-mediated immune response and orbital tissue damage. The anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies produced by B ly...

Atypical skin conditions of the neck and back as a dermal manifestation of anti-HMGCR antibody-positive myopathy

Immune-mediated necrotizing myopathy (IMNM) is an idiopathic inflammatory myopathy (IIM). Though patients with IMNM were not considered to show skin rash, several reports have showed atypical skin conditions i...

GNUV201, a novel human/mouse cross-reactive and low pH-selective anti-PD-1 monoclonal antibody for cancer immunotherapy

Several PD-1 antibodies approved as anti-cancer therapies work by blocking the interaction of PD-1 with its ligand PD-L1, thus restoring anti-cancer T cell activities. These PD-1 antibodies lack inter-species ...

Effect of immune-modulating metronomic capecitabine as an adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma

Metronomic capecitabine used as an adjuvant therapy improves survival in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC). This therapeutic approach may also contribute to improving immu...

A novel chimeric vaccine containing multiple epitopes for simulating robust immune activation against Klebsiella pneumoniae

Due to antibiotic resistance, the Klebsiella genus is linked to morbidity and death, necessitating the development of a universally protective vaccine against Klebsiella pathogens.

The role of the immune system in early-onset schizophrenia: identifying immune characteristic genes and cells from peripheral blood

Early-onset schizophrenia (EOS) is a type of schizophrenia (SCZ) with an age of onset of < 18 years. An abnormal inflammatory immune system may be involved in the occurrence and development of SCZ. We aimed to...

Atypical memory B cells increase in the peripheral blood of patients with breast cancer regardless of lymph node involvement

Breast cancer is the most common cancer in females. The immune system has a crucial role in the fight against cancer. B and T cells, the two main components of the adaptive immunity, are critical players that ...

The influence of neonatal BCG vaccination on in vitro cytokine responses to Plasmodium falciparum

Bacillus Calmette–Guérin (BCG) vaccination has off-target protective effects against infections unrelated to tuberculosis. Among these, murine and human studies suggest that BCG vaccination may protect against...

Basophil activation in insect venom allergy: comparison of an established test using liquid reagents with a test using 5-color tubes with dried antibody reagents

Flow cytometry-based basophil activation tests (BAT) have been performed with various modifications, differing in the use of distinct identification and activation markers. Established tests use liquid reagent...

Advanced in immunological monitoring of HIV infection: profile of immune cells and cytokines in people living with HIV-1 in Benin

Immune cells and cytokines have been linked to viremia dynamic and immune status during HIV infection. They may serve as useful biomarkers in the monitoring of people living with HIV-1 (PLHIV-1). The present w...

Helminth-derived proteins as immune system regulators: a systematic review of their promise in alleviating colitis

Helminth-derived proteins have immunomodulatory properties, influencing the host’s immune response as an adaptive strategy for helminth survival. Helminth-derived proteins modulate the immune response by induc...

Association of interleukin-17A and chemokine/vascular endothelial growth factor-induced angiogenesis in newly diagnosed patients with bladder cancer

The human interleukin-17 (IL-17) family comprises IL-17A to IL-17 F; their receptors are IL-17RA to IL-17RE. Evidence revealed that these cytokines can have a tumor-supportive or anti-tumor impact on human mal...

Causal relationship between immune cells and telomere length: mendelian randomization analysis

The causal relationship between immune cells and telomere length remains controversial.

Subcutaneous immunoglobulin replacement therapy in patients with immunodeficiencies – impact of drug packaging and administration method on patient reported outcomes

Here, the perspective of patients with primary and secondary immunodeficiency receiving subcutaneous immunoglobulin (SCIg) via introductory smaller size pre-filled syringes (PFS) or vials were compared.

Dendritic cells under allergic condition enhance the activation of pruritogen-responsive neurons via inducing itch receptors in a co-culture study

Itch sensitization has been reported in patients with chronic allergic skin diseases and observed in a mouse model of allergic contact dermatitis (ACD). There is evidence suggesting that neuroimmune interactio...

Network pharmacology-based strategy to investigate the mechanisms of artemisinin in treating primary Sjögren’s syndrome

The study aimed to explore the mechanism of artemisinin in treating primary Sjögren’s syndrome (pSS) based on network pharmacology and experimental validation.

Hyperactivation and enhanced cytotoxicity of reduced CD8 + gamma delta T cells in the intestine of patients with Crohn’s disease correlates with disease activity

We aimed to investigate the immune characteristics of intestinal CD8 + gamma delta T (CD8 + γδ T) cells in Crohn’s disease (CD) and their correlation with disease activity.

Immune responses to P falciparum antibodies in symptomatic malaria patients with variant hemoglobin genotypes in Ghana

Haemoglobin (Hb) variants such as sickle cell trait (SCT/HbAS) play a role in protecting against clinical malaria, but little is known about the development of immune responses against malaria parasite ( Plasmodiu...

Systematic evaluation of B-cell clonal family inference approaches

The reconstruction of clonal families (CFs) in B-cell receptor (BCR) repertoire analysis is a crucial step to understand the adaptive immune system and how it responds to antigens. The BCR repertoire of an ind...

Expression of the immune checkpoint molecules CD226 and TIGIT in preeclampsia patients

Imbalanced immune responses are involved in developing preeclampsia (PE). We wish to explore the expression and potential changes of immune checkpoint molecules TIGIT, CD226 and CD155 in PE patients.

Oral administration of DNA alginate nanovaccine induced immune-protection against Helicobacter pylori in Balb/C mice

Helicobacter pylori (H. Pylori), is an established causative factor for the development of gastric cancer and the induction of persistent stomach infections that may lead to peptic ulcers. In recent decades, s...

Profiling of T cell repertoire in peripheral blood of patients from type 2 diabetes with complication

More than 90% of patients with diabetes worldwide are type 2 diabetes (T2D), which is caused by insulin resistance or impaired producing insulin by pancreatic β cells. T2D and its complications, mainly large c...

Tumor microenvironment and immune system preservation in early-stage breast cancer: routes for early recurrence after mastectomy and treatment for lobular and ductal forms of disease

Intra-ductal cancer (IDC) is the most common type of breast cancer, with intra-lobular cancer (ILC) coming in second. Surgery is the primary treatment for early stage breast cancer. There are now irrefutable d...

Predictive biomarkers for immune-related adverse events in cancer patients treated with immune-checkpoint inhibitors

The objective of this study was to identify potential predictors of immune-related adverse events (irAEs) in cancer patients receiving immune checkpoint inhibitor therapy among serum indexes, case data, and li...

Negative prognostic behaviour of PD-L1 expression in tongue and larynx squamous cell carcinoma and its significant predictive power in combination with PD-1 expression on TILs

Biomarkers that can predict outcome will improve the efficacy of treatment for HNSCC patients. In this regard, we retrospectively evaluated the prognostic effect of PD1, PD-L1, and CD45RO in tongue and larynx ...

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Single-Cell Sequencing: High-Resolution Analysis of Cellular Heterogeneity in Autoimmune Diseases

• Published: 26 August 2024

Cite this article

• Xuening Tang 1 , 2 , 3 ,
• Yudi Zhang 1 ,
• Hao Zhang 4 ,
• Nan Zhang 5 ,
• Ziyu Dai 2 , 3 ,
• Quan Cheng 2 , 3 &
• Yongzhen Li 1  

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Autoimmune diseases (AIDs) are complex in etiology and diverse in classification but clinically show similar symptoms such as joint pain and skin problems. As a result, the diagnosis is challenging, and usually, only broad treatments can be available. Consequently, the clinical responses in patients with different types of AIDs are unsatisfactory. Therefore, it is necessary to conduct more research to figure out the pathogenesis and therapeutic targets of AIDs. This requires research technologies with strong extraction and prediction capabilities. Single-cell sequencing technology analyses the genomic, epigenomic, or transcriptomic information at the single-cell level. It can define different cell types and states in greater detail, further revealing the molecular mechanisms that drive disease progression. These advantages enable cell biology research to achieve an unprecedented resolution and scale, bringing a whole new vision to life science research. In recent years, single-cell technology especially single-cell RNA sequencing (scRNA-seq) has been widely used in various disease research. In this paper, we present the innovations and applications of single-cell sequencing in the medical field and focus on the application contributing to the differential diagnosis and precise treatment of AIDs. Despite some limitations, single-cell sequencing has a wide range of applications in AIDs. We finally present a prospect for the development of single-cell sequencing. These ideas may provide some inspiration for subsequent research.

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The Application of Single-Cell RNA Sequencing in Studies of Autoimmune Diseases: a Comprehensive Review

Research progress on the application of single-cell sequencing in autoimmune diseases

Single-cell analysis in rheumatic and allergic diseases: insights for clinical practice

Availability of data and materials.

No datasets were generated or analysed during the current study.

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Acknowledgements

We would like to express our gratitude to Figdraw, who provided technical support for the drawing of the figures in this article.

This work was supported by the Hunan Provincial Health Committee Foundation of China (No. B202306017169), the Changsha Natural Science Foundation (No. kq2208314), the National Key R&D Program of China (No. 2021YFC2702004), and the Hunan Youth Science and Technology Talent Project (No. 2023RC3074).

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Xuening Tang, Ziyu Dai & Quan Cheng

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Department of Neurosurgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China

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Tang, X., Zhang, Y., Zhang, H. et al. Single-Cell Sequencing: High-Resolution Analysis of Cellular Heterogeneity in Autoimmune Diseases. Clinic Rev Allerg Immunol (2024). https://doi.org/10.1007/s12016-024-09001-6

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Research Reveals Potential Target for Immune Diseases

A medical mystery served as the genesis for a Yale-led study that has promising implications for treating a range of autoimmune diseases.

A young girl entered the clinic suffering from blood cell abnormalities, difficulty breathing, and later, diarrhea. She also had been diagnosed with recurrent infections due to low levels of antibody production. Her doctors treated her with corticosteroids to reduce her lung and gut inflammation and immunoglobulin replacement therapy to restore her antibody levels.

The lab of Carrie Lucas, PhD , associate professor of immunobiology at Yale School of Medicine, works with children living with rare immune disorders that stem from a single (monogenic) gene mutation with the goal of better understanding the intricate circuitry of human immunology.

Through genome sequencing, Lucas discovered that the girl’s symptoms were caused by mutations that created a deficiency in phosphatidylinositol 3-kinase-gamma (PI3Kγ), a signaling molecule that is found in immune cells. Immune defects caused by this mutation, the research team found, were driving immune-mediated damage in the girl’s gut and lungs, and also decreasing her antibody levels. The team published its initial discovery in September 2019 in Nature Communications .

The discovery spurred Lucas’ team to dig deeper into the biological connection between PI3Kγ and antibody response. Now, the scientists have found that PI3Kγ plays an essential role in allowing activated B cells, a type of immune cell, to differentiate into antibody-secreting cells. Beyond helping to understand disease from rare cases of human PI3Kγ deficiency, the researchers hope that other patients can also benefit from this new knowledge. By therapeutically blocking PI3Kγ, clinicians might be able to treat the overproduction of antibodies that causes the symptoms of many autoimmune diseases. The team published its new findings in Nature Immunology on July 3.

“These sorts of monogenic, single-gene defect diseases help us learn fundamental biology directly from patients,” says Lucas, who was the study’s principal investigator. “We’re excited that this could potentially help us find a new way to intervene in autoimmunity.”

How do B cells become antibody-producing cells?

Antibodies are one of the key components of the adaptive (or acquired) immune system and target foreign invaders such as bacteria or viruses. B cells play a vital role in antibody production and in immune memory that protects us from reinfection.

We’re excited that this could potentially help us find a new way to intervene in autoimmunity. Carrie Lucas, PhD

B cells become activated when an antigen [a substance that triggers the body’s immune response] binds to its receptors. Once activated, B cells form what are called “germinal centers.” “We think of germinal centers as factories for B cells to become optimal antibody secreters and choose cell fates to support that function,” says Lucas.

B cells have multiple potential fates, including becoming memory cells or antibody-secreting cells (ASC). The role of memory cells is to “remember” specific antigens so that the body can more rapidly initiate an immune response if the antigen returns. In turn, ASCs begin releasing very large amounts of antibodies that target the intruder into the blood. However, immunobiologists have not understood all the details of the differentiation process of B cells.

PI3Kγ plays essential role in B cell differentiation

Inspired by their patient’s genetic mutation and low antibody levels, Lucas’ team sought to explore the potential role of PI3Kγ in antibody production.

First, they needed to create a mouse version of their human patient. So, the team used genetically modified mice in which PI3Kγ was knocked out. Back in 2019, they tested these mice by emulating how humans, unlike "clean" laboratory mice, live in an environment filled with microbes. “Knockout” and control lab mice were exposed to ones from a pet store, to introduce microbes into the lab mice that the animals had never experienced while isolated in the lab. The researchers found that the knockout mice (lacking PI3Ky) also had defective antibody production following exposure to these new antigens from the pet store mice. “This told us that this kinase is critical for antibodies in mice just as it is in humans,” says Lucas.

Fast forward to their latest publication—now, the researchers wanted to know which specific types of immune cells use PI3Kγ. So, they created various mouse models in which PI3Kγ was knocked out of only one type of immune cell, such as B cells, T cells, macrophages, or dendritic cells. Then, they immunized the mice and measured antibody production. They discovered that removing PI3Kγ specifically from B cells created nearly identical reductions in antibody response to what they had seen in their patient. “This was our first dive into what was going on in the immune system—B cells require this kinase for them to function properly,” says Lucas.

Next, the researchers wanted to elucidate what role PI3Kγ plays in B cells during an immune response. Their models revealed that PI3Kγ was not important during activation or germinal center formation, but rather during a B cell’s differentiation into an ASC.

PI3Kγ inhibitors could potentially treat autoimmune diseases

Lucas is excited by these findings, which started with patient-driven discovery, and their relevance for human health. Her team identified not only a major player in how B cells choose to differentiate but also a potential target for treating autoimmune diseases. Current treatments for autoimmune diseases often include completely wiping out B cells. “This can be quite helpful but is also setting the patient up to be at risk for infections,” she says.

PI3Kγ inhibitors are already used to treat certain cancers and rare diseases. Could these drugs also help restore an overactive immune system? she wondered.

To begin to investigate, her group teamed up with Neil D. Romberg, MD , associate professor of pediatrics (allergy/immunology) at the Children’s Hospital of Philadelphia, and his colleagues for studies in human tonsil organoid models. After treating the models with a PI3Kγ-targeting drug, the researchers found it successfully blocked B cells’ ability to differentiate into ASCs. “This gives us direct human data paired with our mouse data to boost our confidence that our findings are relevant for shutting off ongoing antibody responses,” Lucas says.

In future studies, Lucas’ team plans to test PI3Kγ inhibitors in pre-clinical autoimmunity mouse models to further evaluate them as potential treatment options. Her team’s work emphasizes how studying rare genetic diseases can also provide broader insights that are significant to a larger proportion of the population, she says.

“Here, we started with a patient, learned what gene is affected, and then followed that thread to find a new level of mechanistic understanding,” she says. “This enabled us to take new insights that come from a totally different field—in this case, immunodeficiency—and now move toward applying it to autoimmunity.”

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