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  1. Article ; Online: Must Reads for Clinicians Seeking a Better Understanding of Primary Immune Deficiency Disorders and Related Disorders.

    Ballow, Mark / Ziegler, John B

    The journal of allergy and clinical immunology. In practice

    2023  Volume 11, Issue 6, Page(s) 1703–1705

    MeSH term(s) Humans ; Primary Immunodeficiency Diseases
    Language English
    Publishing date 2023-04-23
    Publishing country United States
    Document type Editorial
    ZDB-ID 2843237-X
    ISSN 2213-2201 ; 2213-2198
    ISSN (online) 2213-2201
    ISSN 2213-2198
    DOI 10.1016/j.jaip.2023.04.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Practical aspects of immunoglobulin replacement.

    Ballow, Mark

    Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology

    2017  Volume 119, Issue 4, Page(s) 299–303

    Language English
    Publishing date 2017-10
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1228189-x
    ISSN 1534-4436 ; 0003-4738 ; 1081-1206
    ISSN (online) 1534-4436
    ISSN 0003-4738 ; 1081-1206
    DOI 10.1016/j.anai.2017.07.020
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  3. Article ; Online: Reply to "Patient variability in severity of COVID-19 disease. Main suspect: vascular endothelium".

    Ballow, Mark / Haga, Christopher L

    The journal of allergy and clinical immunology. In practice

    2021  Volume 9, Issue 6, Page(s) 2541–2542

    MeSH term(s) COVID-19 ; Endothelium, Vascular ; Humans ; SARS-CoV-2
    Language English
    Publishing date 2021-06-10
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 2843237-X
    ISSN 2213-2201 ; 2213-2198
    ISSN (online) 2213-2201
    ISSN 2213-2198
    DOI 10.1016/j.jaip.2021.03.031
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  4. Article ; Online: Precision Medicine in the Treatment of Primary Immune Deficiency Patients With Disorders of Immune Dysregulation.

    Ballow, Mark / Leiding, Jennifer W

    Clinical reviews in allergy & immunology

    2021  Volume 63, Issue 1, Page(s) 1–8

    Abstract: There are now more than 450 described monogenic germline mutations for inborn errors of immunity that result in the loss of expression, loss of function (LOF), or gain in function (GOF) of the encoded protein. Molecular characterization of these inborn ... ...

    Abstract There are now more than 450 described monogenic germline mutations for inborn errors of immunity that result in the loss of expression, loss of function (LOF), or gain in function (GOF) of the encoded protein. Molecular characterization of these inborn errors of immunity has not only allowed us to characterize on a genetic basis these immune deficiency disorders but has provided a better understanding of the immunobiology of these inborn errors of immunity. More recently, these advances have allowed us to apply targeted therapy or precision medicine in their treatment. Of particular interest related to this review are those inborn errors of immunity that result in gain-of-function (GOF) genetic abnormalities. Many of these inborn errors of immunity fall into a new category referred to as diseases of immune dysregulation in which many of the patients not only exhibit an increased susceptibility to infection but also have a clinical phenotype associated with autoimmune processes and lymphoproliferative disease.
    MeSH term(s) Humans ; Immunologic Deficiency Syndromes/drug therapy ; Immunologic Deficiency Syndromes/therapy ; Phenotype ; Precision Medicine ; Primary Immunodeficiency Diseases/genetics ; Primary Immunodeficiency Diseases/therapy
    Language English
    Publishing date 2021-06-24
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 1239045-8
    ISSN 1559-0267 ; 1080-0549
    ISSN (online) 1559-0267
    ISSN 1080-0549
    DOI 10.1007/s12016-021-08871-4
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  5. Article ; Online: Why Do Some People Develop Serious COVID-19 Disease After Infection, While Others Only Exhibit Mild Symptoms?

    Ballow, Mark / Haga, Christopher L

    The journal of allergy and clinical immunology. In practice

    2021  Volume 9, Issue 4, Page(s) 1442–1448

    Abstract: The year 2020 was a landmark year of a once-in-a-century pandemic of a novel coronavirus, SARS-CoV-2 virus, that led to a rapidly spreading coronavirus disease (COVID-19). The spectrum of disease with SARS-CoV-2 ranges from asymptomatic to mild upper ... ...

    Abstract The year 2020 was a landmark year of a once-in-a-century pandemic of a novel coronavirus, SARS-CoV-2 virus, that led to a rapidly spreading coronavirus disease (COVID-19). The spectrum of disease with SARS-CoV-2 ranges from asymptomatic to mild upper respiratory illness, to moderate to severe disease with respiratory compromise to acute respiratory distress syndrome, multiorgan failure, and death. Early in the pandemic, risk factors were recognized that contributed to more severe disease, but it became evident that individuals and even young people could have severe COVID-19. As we started to understand the immunobiology of COVID-19, it became clearer that the immune responses to SARS-CoV-2 were variable, and in some cases, the excessive inflammatory response contributed to greater morbidity and mortality. In this review, we will explore some of the additional risk factors that appear to contribute to disease severity and enhance our understanding of why some individuals experience more severe COVID-19. Recent advances in genome-wide associations have identified potential candidate genes in certain populations that may modify the host immune responses leading to dysregulated host immunity. Genetic defects of the type I interferon pathway are also linked to a more clinically severe phenotype of COVID-19. Finally, dysregulation of the adaptive immune system may also play a role in the severity and complex clinical course of patients with COVID-19. A better understanding of the host immune responses to SARS-CoV-2 will hopefully lead to new treatment modalities to prevent the poor outcomes of COVID-19 in those individuals with pre-existing risk factors or genetic variants that contribute to the dysregulated host immune responses.
    MeSH term(s) Adaptive Immunity ; COVID-19/diagnosis ; COVID-19/pathology ; Genome-Wide Association Study ; Humans ; Immunity/genetics ; Multiple Organ Failure/virology ; Pandemics ; Respiratory Distress Syndrome/virology ; Risk Factors
    Language English
    Publishing date 2021-01-21
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2843237-X
    ISSN 2213-2201 ; 2213-2198
    ISSN (online) 2213-2201
    ISSN 2213-2198
    DOI 10.1016/j.jaip.2021.01.012
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  6. Article ; Online: Advances and Challenges of the Decade: The Ever-Changing Clinical and Genetic Landscape of Immunodeficiency.

    Walter, Jolan E / Ziegler, John B / Ballow, Mark / Cunningham-Rundles, Charlotte

    The journal of allergy and clinical immunology. In practice

    2023  Volume 11, Issue 1, Page(s) 107–115

    Abstract: In the past 10 years, we have witnessed major advances in clinical immunology. Newborn screening for severe combined immunodeficiency has become universal in the United States and screening programs are being extended to severe combined immunodeficiency ... ...

    Abstract In the past 10 years, we have witnessed major advances in clinical immunology. Newborn screening for severe combined immunodeficiency has become universal in the United States and screening programs are being extended to severe combined immunodeficiency and other inborn errors of immunity globally. Early genetic testing is becoming the norm for many of our patients and allows for informed selection of targeted therapies including biologics repurposed from other specialties. During the COVID-19 pandemic, our understanding of essential immune responses expanded and the discovery of immune gene defects continued. Immunoglobulin products, the backbone of protection for antibody deficiency syndromes, came into use to minimize side effects. New polyclonal and monoclonal antibody products emerged with increasing options to manage respiratory viral agents such as SARS-CoV-2 and respiratory syncytial virus. Against these advances, we still face major challenges. Atypical is becoming typical as phenotypes of distinct genetic disease overlap whereas the clinical spectrum of the same genetic defect widens. Therefore, clinical judgment needs to be paired with repeated deep immune phenotyping and upfront genetic testing, as technologies rapidly evolve, and clinical disease often progresses with age. Managing patients with organ damage resulting from immune dysregulation poses a special major clinical challenge and management often lacks standardization, from autoimmune cytopenias, granulomatous interstitial lung disease, enteropathy, and liver disease to endocrine, rheumatologic, and neurologic complications. Clinical, translational, and basic science networks will continue to advance the field; however, cross-talk and education with practicing allergists/immunologists are essential to keep up with the ever-changing clinical and genetic landscape of inborn errors of immunity.
    MeSH term(s) Humans ; Severe Combined Immunodeficiency ; Pandemics ; COVID-19/complications ; SARS-CoV-2 ; Immunologic Deficiency Syndromes/genetics
    Language English
    Publishing date 2023-01-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2843237-X
    ISSN 2213-2201 ; 2213-2198
    ISSN (online) 2213-2201
    ISSN 2213-2198
    DOI 10.1016/j.jaip.2022.11.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Secondary Immune Deficiency and Primary Immune Deficiency Crossovers: Hematological Malignancies and Autoimmune Diseases.

    Ballow, Mark / Sánchez-Ramón, Silvia / Walter, Jolan E

    Frontiers in immunology

    2022  Volume 13, Page(s) 928062

    Abstract: Primary immunodeficiencies (PIDs), a heterogenous group of inborn errors of immunity, are predetermined at birth but may evolve with age, leading to a variable clinical and laboratory presentation. In contrast, secondary immunodeficiencies (SIDs) are ... ...

    Abstract Primary immunodeficiencies (PIDs), a heterogenous group of inborn errors of immunity, are predetermined at birth but may evolve with age, leading to a variable clinical and laboratory presentation. In contrast, secondary immunodeficiencies (SIDs) are acquired declines of immune cell counts and or/function. The most common type of SID is a decreased antibody level occurring as a consequence of extrinsic influences, such as an underlying condition or a side effect of some medications used to treat hematological malignancies and autoimmune disorders. Paradoxically, immune deficiencies initially attributed to secondary causes may partly be due to an underlying PID. Therefore, in the era of immune-modulating biologicals, distinguishing between primary and secondary antibody deficiencies is of great importance. It can be difficult to unravel the relationship between PID, SID and hematological malignancy or autoimmunity in the clinical setting. This review explores SID and PID crossovers and discusses challenges to diagnosis and treatment strategies. The case of an immunodeficient patient with follicular lymphoma treated with rituximab illustrates how SID in the setting of hematological cancer can mask an underlying PID, and highlights the importance of screening such patients. The risk of hematological cancer is increased in PID: for example, lymphomas in PID may be driven by infections such as Epstein-Barr virus, and germline mutations associated with PID are enriched among patients with diffuse large B-cell lymphoma. Clues suggesting an increased risk of hematological malignancy in patients with common variable immune deficiency (CVID) are provided, as well as pointers for distinguishing PID versus SID in lymphoma patients. Two cases of patients with autoimmune disorders illustrate how an apparent rituximab-induced antibody deficiency can be connected to an underlying PID. We highlight that PID is increasingly recognized among patients with autoimmune cytopenias, and provide guidance on how to identify PID and distinguish it from SID in such patients. Overall, healthcare professionals encountering patients with malignancy and/or autoimmunity who have post-treatment complications of antibody deficiencies or other immune abnormalities need to be aware of the possibility of PID or SID and how to differentiate them.
    MeSH term(s) Autoimmune Diseases ; Epstein-Barr Virus Infections/complications ; Hematologic Neoplasms/complications ; Herpesvirus 4, Human ; Humans ; Immunologic Deficiency Syndromes/genetics ; Infant, Newborn ; Primary Immunodeficiency Diseases/diagnosis ; Rituximab ; Sudden Infant Death
    Chemical Substances Rituximab (4F4X42SYQ6)
    Language English
    Publishing date 2022-07-18
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.928062
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  8. Article ; Online: Redefining Precision Medicine in Disorders of Immune Dysregulation.

    Leiding, Jennifer W / Ballow, Mark

    The journal of allergy and clinical immunology. In practice

    2020  Volume 7, Issue 8, Page(s) 2801–2803

    MeSH term(s) Abatacept ; Precision Medicine
    Chemical Substances Abatacept (7D0YB67S97)
    Language English
    Publishing date 2020-02-10
    Publishing country United States
    Document type Editorial ; Comment
    ZDB-ID 2843237-X
    ISSN 2213-2201 ; 2213-2198
    ISSN (online) 2213-2201
    ISSN 2213-2198
    DOI 10.1016/j.jaip.2019.07.026
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  9. Article ; Online: Primary Immune Deficiencies: Update on an Evolving Clinical Discipline.

    Ballow, Mark / Perez, Elena E

    Immunology and allergy clinics of North America

    2020  Volume 40, Issue 3, Page(s) ix–xi

    Language English
    Publishing date 2020-06-07
    Publishing country United States
    Document type Editorial ; Introductory Journal Article
    ZDB-ID 92606-1
    ISSN 1557-8607 ; 0889-8561
    ISSN (online) 1557-8607
    ISSN 0889-8561
    DOI 10.1016/j.iac.2020.05.001
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  10. Article ; Online: Diagnosis and management of Specific Antibody Deficiency.

    Perez, Elena E / Ballow, Mark

    Immunology and allergy clinics of North America

    2020  Volume 40, Issue 3, Page(s) 499–510

    Abstract: Specific antibody deficiency is a primary immunodeficiency disease recognized by the International Union of Immunology Societies and defined by recurrent respiratory infections with normal immunoglobulins, but diminished antibody responses to ... ...

    Abstract Specific antibody deficiency is a primary immunodeficiency disease recognized by the International Union of Immunology Societies and defined by recurrent respiratory infections with normal immunoglobulins, but diminished antibody responses to polysaccharide antigens after vaccination with the 23 valent pneumococcal polysaccharide vaccine. Clinical immunologists struggle with diagnosis and treatment, because the definition of an adequate response to immunization remains controversial. Specific antibody deficiency is managed clinically with close follow-up and prompt treatment of infections, antibiotic prophylaxis, or immune globulin therapy. Treatment is individualized using clinical judgment and existing practice guidelines, which will likely evolve as more studies become available.
    MeSH term(s) Agammaglobulinemia/complications ; Agammaglobulinemia/diagnosis ; Agammaglobulinemia/etiology ; Agammaglobulinemia/therapy ; Clinical Decision-Making ; Combined Modality Therapy ; Disease Management ; Disease Susceptibility ; Humans ; Immunocompromised Host ; Infection Control ; Infections/diagnosis ; Infections/etiology ; Infections/therapy ; Phenotype ; Primary Immunodeficiency Diseases/complications ; Primary Immunodeficiency Diseases/diagnosis ; Primary Immunodeficiency Diseases/etiology ; Primary Immunodeficiency Diseases/therapy ; Treatment Outcome ; Vaccination ; Vaccines/administration & dosage
    Chemical Substances Vaccines
    Language English
    Publishing date 2020-06-09
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 92606-1
    ISSN 1557-8607 ; 0889-8561
    ISSN (online) 1557-8607
    ISSN 0889-8561
    DOI 10.1016/j.iac.2020.03.005
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