Could Immune Checkpoint Disorders and EBV Reactivation Be Connected in the Development of Hematological Malignancies in Immunodeficient Patients?

Article Pathology

Diagnostic Utility of CD200 Immunohistochemistry in Distinguishing EBV-Positive Large B-Cell Lymphoma From Classic Hodgkin Lymphoma

Christopher Batuello et al.

Summary: CD200 expression can differentiate EBV+ LBCL from CHL, with negative or partial/weak staining favoring a diagnosis of EBV+ LBCL and strong diffuse staining favoring a diagnosis of CHL.

AMERICAN JOURNAL OF CLINICAL PATHOLOGY (2023)

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Article Medicine, General & Internal

Immune checkpoint inhibitors are effective in the treatment of Epstein-Barr virus-associated gastric cancer: A case report

Gaili An et al.

Summary: Gastric cancer is a common malignancy globally, and Epstein-Barr virus-associated gastric cancer has become a research hotspot. In advanced gastric cancer, Epstein-Barr virus infection is closely related to poor prognosis, and there is a need for new treatment modalities. Immune checkpoint inhibitors have shown clinical benefits and few adverse effects in patients with gastric cancer.

MEDICINE (2023)

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Review Virology

Epstein-Barr Virus History and Pathogenesis

Hui Yu et al.

Summary: Epstein-Barr virus (EBV) is the first oncogenic virus identified in humans that can establish lifelong asymptomatic persistence. It is associated with a wide range of diseases, including both benign and malignant conditions. Although there have been continuous studies on the molecular biology and diseases related to EBV for nearly 60 years, the mechanism of viral-mediated transformation and the precise role of EBV in these diseases are still major challenges that require further exploration.

VIRUSES-BASEL (2023)

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Review Virology

The Role of Viral Infections in the Onset of Autoimmune Diseases

Bhargavi Sundaresan et al.

Summary: Autoimmune diseases result from a breakdown in immune tolerance, leading to an inability to distinguish between self and non-self. Immune reactions targeting self-antigens can cause destruction of host cells and the development of autoimmune diseases. Although relatively rare, autoimmune disorders are increasing globally and have significant implications for mortality and morbidity. Genetic and environmental factors are believed to be major contributors to autoimmunity, with viral infections being one environmental trigger. Current research suggests that viral-induced autoimmunity can be caused by mechanisms such as molecular mimicry, epitope spreading, and bystander activation. This article describes the latest understanding of the pathomechanisms of viral-induced autoimmune diseases and discusses recent findings on COVID-19 infections and the development of autoimmune diseases.

VIRUSES-BASEL (2023)

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Article Immunology

Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors

Luzia Bruns et al.

Summary: This study investigated the prevalence of cancer and associated clinical, immunological, and genetic factors in a German cohort of patients with common variable immunodeficiency (CVID). The results showed that gastric cancer, non-melanoma skin cancer (NMSC), and non-Hodgkin lymphoma (NHL) were the most common types of cancer in CVID patients. Immune dysregulation manifested as arthritis, atrophic gastritis, or interstitial lung disease (ILD) was found to be associated with the diagnosis of cancer. The study concluded that studied immunological parameters or the identification of a monogenic form of CVID have a limited role in evaluating cancer risk in CVID.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Oncology

Expression of CTLA-4 and CD86 Antigens and Epstein-Barr Virus Reactivation in Chronic Lymphocytic Leukemia-Any Link with Known Prognostic Factors?

Ewelina Grywalska et al.

Summary: This study assessed whether Epstein-Barr virus (EBV) affects the course of chronic lymphocytic leukemia (CLL) by deregulating the CTLA-4/CD86 signaling pathway. The results showed that EBV infection worsens the prognosis in CLL and is associated with up-regulation of CTLA-4 expression.

CANCERS (2022)

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Article Hematology

EBV-positive diffuse large B-cell lymphoma, not otherwise specified: 2022 update on diagnosis, risk-stratification, and management

Luis Malpica et al.

Summary: EBV+ DLBCL, NOS is an aggressive B-cell lymphoma associated with EBV infection, diagnosed through careful pathological evaluation. Risk-stratification can be done using IPI and Oyama score, with emerging potential biomarkers being CD30 and PD-1/PD-L1 expression.

AMERICAN JOURNAL OF HEMATOLOGY (2022)

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Article Oncology

Efficacy and predictive biomarkers of immunotherapy in Epstein-Barr virus-associated gastric cancer

Yuezong Bai et al.

Summary: In this study, an efficient next-generation sequencing (NGS) based algorithm was developed and validated for detecting Epstein-Barr virus (EBV) infection in gastric cancer (GC). EBV infection was found to be an independent predictive factor for immune checkpoint blockade (ICB) efficacy in GC, and CTLA-4, tumor mutational burden (TMB), and SMARCA4 mutation were identified as potential predictive biomarkers for ICB efficacy in EBV-associated GC (EBVaGC).

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

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Review Biochemistry & Molecular Biology

The Epstein-Barr Virus Hacks Immune Checkpoints: Evidence and Consequences for Lymphoproliferative Disorders and Cancers

Alison Felipe Bordini Biggi et al.

Summary: The Epstein-Barr Virus (EBV) is involved in the development of various human cancers and may interfere with immune checkpoint molecules. This has implications for the clinical management of EBV-associated malignancies.

BIOMOLECULES (2022)

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Article Pathology

Association of PD-1/PD-L1 expression and Epstein--Barr virus infection in patients with invasive breast cancer

Wei-tong Zhang et al.

Summary: This study analyzed the clinicopathological features of EBV-positive IBC and found that EBV infection affects PD-1/PD-L1 expression, similar to other EBV-infected tumors. This finding could be used as a basis to explore therapeutic targets, particularly immunotherapy, for patients with IBC.

DIAGNOSTIC PATHOLOGY (2022)

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Review Immunology

Secondary Immune Deficiency and Primary Immune Deficiency Crossovers: Hematological Malignancies and Autoimmune Diseases

Mark Ballow et al.

Summary: Primary immunodeficiencies (PIDs) are genetic immune errors determined at birth, while secondary immunodeficiencies (SIDs) are acquired diseases with decreased immune cell counts. Distinguishing between primary and secondary antibody deficiencies is crucial in the era of immune-modulating biologicals. This article explores the crossovers between SIDs and PIDs, and discusses the challenges in diagnosis and treatment.

FRONTIERS IN IMMUNOLOGY (2022)

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Review Immunology

Autoimmune Cytopenias in Common Variable Immunodeficiency Are a Diagnostic and Therapeutic Conundrum: An Update

Sanchi Chawla et al.

Summary: Common variable immunodeficiency (CVID) is a heterogenous condition with various clinical manifestations, ranging from increased susceptibility to infections to autoimmune manifestations, granulomatous disease, polyclonal lymphoproliferation, and increased risk of malignancy. Autoimmune cytopenias, specifically autoimmune haemolytic anaemia and/or thrombocytopenia, are the most common autoimmune complications seen in patients with CVID. Diagnosis and treatment of these complications can be challenging. Checking serum immunoglobulins in patients with autoimmune cytopenia such as immune thrombocytopenia or autoimmune haemolytic anaemia is recommended.

FRONTIERS IN IMMUNOLOGY (2022)

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Review Immunology

Genetics of Immune Dysregulation and Cancer Predisposition: Two Sides of the Same Coin

Sigal Matza Porges et al.

Summary: Approximately 10% of cancers have a hereditary predisposition, but genetic diagnosis is not available in 60%-80% of familial cancers. Immune dysregulation-mediated diseases are frequent in some of these families, and dysregulation of the immune system can increase the risk of developing cancer. Genetic counseling currently focuses on known genes that raise the risk of cancer, but for missing hereditary familial cases, the family history of immune dysregulation should be recorded and analyzed for genes related to the immune system. Patients with immune disorders diagnosed with a pathogenic mutation in an immune regulatory gene may have an increased risk of cancer and require surveillance. Gene panel and exome sequencing are standard methods for genetic diagnosis, providing an opportunity to test cancer and immune genes together.

CLINICAL AND EXPERIMENTAL IMMUNOLOGY (2022)

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Review Immunology

EBV-associated diseases: Current therapeutics and emerging technologies

Srishti Chakravorty et al.

Summary: EBV is a prevalent virus with a high infection rate, which is associated with cancer and autoimmune diseases. Despite some available treatments, their efficacy and safety are still unclear. Therefore, studying the mechanisms and therapeutic methods related to EBV-associated diseases is crucial for the development of novel effective treatments.

FRONTIERS IN IMMUNOLOGY (2022)

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Review Clinical Neurology

Secondary Immunodeficiency and Risk of Infection Following Immune Therapies in Neurology

Fabian Szepanowski et al.

Summary: Secondary immunodeficiencies (SIDs) are acquired conditions that may occur as a result of immune therapy, particularly through secondary antibody deficiency. Prevention strategies include awareness of risk factors, individualized treatment, and vaccination concepts, while immune supplementation with Ig replacement therapy may reduce morbidity and mortality associated with SIDs in neurological conditions. Recognition of the potential for SIDs is crucial for neurologists and other healthcare professionals given the broad range of existing and emerging therapies.

CNS DRUGS (2021)

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Review Immunology

Epstein-Barr Virus and Systemic Autoimmune Diseases

Gunnar Houen et al.

Summary: Epstein-Barr Virus (EBV) is a highly successful human herpes virus that infects essentially all humans at some point in their lives. EBV primarily spreads through saliva and can lead to infectious mononucleosis. The infection results in an immune response and production of antibodies, which can cause chronic relapsing/reactivating infections.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Oncology

Restoration of the immune function as a complementary strategy to treat Chronic Lymphocytic Leukemia effectively

Carol Moreno et al.

Summary: Chronic Lymphocytic Leukemia is a hematological malignancy characterized by uncontrolled B-cell proliferation and severe immune dysfunction. Developing therapeutic strategies that target both malignant B-cells and enhance the patient's immune response could be clinically relevant in treating CLL patients.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2021)

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Editorial Material Immunology

Primary Immunodeficiencies: A Decade of Progress and a Promising Future

Isabelle Meyts et al.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Immunology

Epstein-Barr Virus plus B Cells in Breast Cancer Immune Response: A Case Report

Andrea Aran et al.

Summary: The study found a restricted T-cell repertoire in tumor tissue during xenograft progression, while T cells from the TNBC biopsy were expanded after transformation into B-cell line, resulting in a limited TCR repertoire. These results suggest that EBV+ B cells infiltrating the tumor as bystanders may interact with tumor-infiltrating T cells and influence the TCR repertoire.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Immunology

Epstein-Barr Virus Epithelial Cancers-A Comprehensive Understanding to Drive Novel Therapies

Shuting Han et al.

Summary: The text discusses the similarities and differences of EBV-associated epithelial cancers (such as NPC, LELC, and EBVaGC), providing a comprehensive description of their clinical, pathological, and molecular characteristics. It emphasizes the importance of research in uncovering targets for future drug development and resistance to immunotherapy.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Immunology

Secondary Immunodeficiency in Hematological Malignancies: Focus on Multiple Myeloma and Chronic Lymphocytic Leukemia

Alessandro Allegra et al.

Summary: Secondary immunodeficiency is common in patients with hematological malignancies, affecting their risk of infection and overall prognosis. Treatment strategies need to be personalized based on individual clinical and immunological conditions, with potential risks associated with vaccination such as decreased immune response and adverse reactions.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Oncology

PD-1 and PD-L1 gene expressions and their association with Epstein-Barr virus infection in chronic lymphocytic leukemia

M. A. Gamaleldin et al.

Summary: The PD-1/PD-L1 pathway is significantly upregulated in CLL patients, associated with EBV infection and poor prognosis, making it a potential therapeutic target.

CLINICAL & TRANSLATIONAL ONCOLOGY (2021)

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Article Oncology

The Triple Positivity for EBV, PD-1, and PD-L1 Identifies a Very High Risk Classical Hodgkin Lymphoma

Vedia Ozturk et al.

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA (2020)

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Review Biochemistry & Molecular Biology

Immune Response Dysfunction in Chronic Lymphocytic Leukemia: Dissecting Molecular Mechanisms and Microenvironmental Conditions

Francesca Arruga et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Article Pathology

High PD-L1 expression in gastric cancer (GC) patients and correlation with molecular features

Xiaoqiao Liu et al.

PATHOLOGY RESEARCH AND PRACTICE (2020)

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Review Public, Environmental & Occupational Health

Risk factors for Epstein Barr virus-associated cancers: a systematic review, critical appraisal, and mapping of the epidemiological evidence

Deniz Bakkalci et al.

JOURNAL OF GLOBAL HEALTH (2020)

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Review Immunology

Immune Dysfunctions and Immune-Based Therapeutic Interventions in Chronic Lymphocytic Leukemia

Valentina Griggio et al.

FRONTIERS IN IMMUNOLOGY (2020)

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Article Oncology

PD-1 inhibition in malignant melanoma and lack of clinical response in chronic lymphocytic leukemia in the same patients: a case series

I Landego et al.

CURRENT ONCOLOGY (2020)

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Review Environmental Sciences

Impact of Gene-Environment Interactions on Cancer Development

Ariane Mbemi et al.

INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH (2020)

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Article Immunology

Leukemic B Cell CTLA-4 Suppresses Costimulation of T Cells

Priscilla Do et al.

JOURNAL OF IMMUNOLOGY (2019)

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Review Immunology

Inflammation and Cancer: Triggers, Mechanisms, and Consequences

Florian R. Greten et al.

IMMUNITY (2019)

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Article Immunology

CVID-Associated Tumors: Czech Nationwide Study Focused on Epidemiology, Immunology, and Genetic Background in a Cohort of Patients With CVID

Pavlina Kralickova et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Review Immunology

Primary Immunodeficiency and Cancer Predisposition Revisited: Embedding Two Closely Related Concepts Into an Integrative Conceptual Framework

Oskar A. Haas

FRONTIERS IN IMMUNOLOGY (2019)

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Article Health Care Sciences & Services

Measuring quality of life of primary antibody deficiency patients using a disease-specific health-related quality of life questionnaire for common variable immunodeficiency (CVID_QoL)

Jintana B. Andersen et al.

JOURNAL OF PATIENT-REPORTED OUTCOMES (2019)

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Article Pathology

PD-1 Expression in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) and Large B-cell Richter Transformation (DLBCL-RT) A Characteristic Feature of DLBCL-RT and Potential Surrogate Marker for Clonal Relatedness

Rong He et al.

AMERICAN JOURNAL OF SURGICAL PATHOLOGY (2018)

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Review Immunology

Increased risk of hematologic malignancies in primary immunodeficiency disorders: opportunities for immunotherapy

Dorit Verhoeven et al.

CLINICAL IMMUNOLOGY (2018)

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Review Biochemistry & Molecular Biology

Common Variable Immunodeficiency and Gastric Malignancies

Patrizia Leone et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2018)

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Article Immunology

Novel Mutations in RASGRP1 are Associated with Immunodeficiency, Immune Dysregulation, and EBV-Induced Lymphoma

Ido Somekh et al.

JOURNAL OF CLINICAL IMMUNOLOGY (2018)

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Review Microbiology

Epstein-Barr Virus-Induced Metabolic Rearrangements in Human B-Cell Lymphomas

Pier P. Piccaluga et al.

FRONTIERS IN MICROBIOLOGY (2018)

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Review Immunology

A Tumor Profile in Primary immune Deficiencies Challenges the Cancer immune Surveillance Concept

Daniel Satge

FRONTIERS IN IMMUNOLOGY (2018)

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Review Immunology

Epstein-Barr Virus Susceptibility in Activated PI3Kδ Syndrome (APDS) Immunodeficiency

Jean-Marie Carpier et al.

FRONTIERS IN IMMUNOLOGY (2018)

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Review Allergy

Primary immunodeficiency

Christine McCusker et al.

ALLERGY ASTHMA AND CLINICAL IMMUNOLOGY (2018)

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Article Medicine, Research & Experimental

Loss of RASGRP1 in humans impairs T-cell expansion leading to Epstein-Barr virus susceptibility

Sarah Winter et al.

EMBO MOLECULAR MEDICINE (2018)

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Article Immunology

Inherited CD70 deficiency in humans reveals a critical role for the CD70-CD27 pathway in immunity to Epstein-Barr virus infection

Kazushi Izawa et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2017)

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Article Multidisciplinary Sciences

PD-L1 predicts poor prognosis for nasopharyngeal carcinoma irrespective of PD-1 and EBV-DNA load

Yajuan Zhou et al.

SCIENTIFIC REPORTS (2017)

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Review Multidisciplinary Sciences

PD-L1 and gastric cancer prognosis: A systematic review and meta-analysis

Lihu Gu et al.

PLOS ONE (2017)

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Review Allergy

Epidemiology and pathophysiology of malignancy in common variable immunodeficiency?

A. Tak Manesh et al.

ALLERGOLOGIA ET IMMUNOPATHOLOGIA (2017)

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Review Oncology

Primary immunodeficiencies associated with EBV-Induced lymphoproliferative disorders

Mahsima Shabani et al.

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY (2016)

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Article Microbiology

PD-1/CTLA-4 Blockade Inhibits Epstein-Barr Virus-Induced Lymphoma Growth in a Cord Blood Humanized-Mouse Model

Shi-Dong Ma et al.

PLOS PATHOGENS (2016)

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Review Immunology

Cancers Related to immunodeficiencies: Update and Perspectives

Esmaeil Mortaz et al.

FRONTIERS IN IMMUNOLOGY (2016)

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Article Immunology

Primary immunodeficiencies and the control of Epstein-Barr virus infection

Umaimainthan Palendira et al.

YEAR IN IMMUNOLOGY (2015)

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Article Immunology

STK4 (MST1) deficiency in two siblings with autoimmune cytopenias: A novel mutation

Sevil Oskay Halacli et al.

CLINICAL IMMUNOLOGY (2015)

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Article Allergy

Novel mutations in TNFRSF7/CD27: Clinical, immunologic, and genetic characterization of human CD27 deficiency

Omar K. Alkhairy et al.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2015)

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Review Oncology

Lymphoproliferative disease and cancer among patients with common variable immunodeficiency

S. Gangemi et al.

LEUKEMIA RESEARCH (2015)

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Review Immunology

Understanding the interplay between host immunity and Epstein-Barr virus in NPC patients

Yong Shen et al.

EMERGING MICROBES & INFECTIONS (2015)

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Article Immunology

Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110 delta result in T cell senescence and human immunodeficiency

Carrie L. Lucas et al.

NATURE IMMUNOLOGY (2014)

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Review Allergy

Autoimmunity in Immunodeficiency

Krista Todoric et al.

CURRENT ALLERGY AND ASTHMA REPORTS (2013)

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Article Allergy

Whole-exome sequencing identifies Coronin-1A deficiency in 3 siblings with immunodeficiency and EBV-associated B-cell lymphoproliferation

Despina Moshous et al.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2013)

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Article Multidisciplinary Sciences

Role of CTLA4 in the Proliferation and Survival of Chronic Lymphocytic Leukemia

Amit K. Mittal et al.

PLOS ONE (2013)

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Article Hematology

The phenotype of human STK4 deficiency

Hengameh Abdollahpour et al.

BLOOD (2012)

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Article Microbiology

Epstein-Barr virus, the immune system, and associated diseases

Mei-Ru Chen

FRONTIERS IN MICROBIOLOGY (2011)

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Review Hematology

How I treat common variable immune deficiency

Charlotte Cunningham-Rundles

BLOOD (2010)

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Article Immunology

The actin regulator coronin 1A is mutant in a thymic egress-deficient mouse strain and in a patient with severe combined immunodeficiency

Lawrence R. Shiow et al.

NATURE IMMUNOLOGY (2008)

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Review Immunology

CD27 and CD70 in T cell and B cell activation

J Borst et al.

CURRENT OPINION IN IMMUNOLOGY (2005)

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Could Immune Checkpoint Disorders and EBV Reactivation Be Connected in the Development of Hematological Malignancies in Immunodeficient Patients?

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