Research Topic

Deciphering the Landscape of Immunohematology: Enhancing our Understanding and Management of Hematological Disorders Through Advances in Immunology and Genetics

About this Research Topic

Immune cytopenias, impacting a single cell lineage or multiple cell lineages, are a frequently encountered primary manifestation of inborn errors of immunity (IEI). Increased awareness and greater clinical availability of diagnostic immunology and molecular-genetic testing, as a means to identify these processes, offer a unique opportunity to provide an early and accurate diagnosis, and to characterize the natural history and treatment responses of an underlying disorder.


Traditionally, autoantibody-mediated processes have been considered the predominant immunologic driver of immune cytopenias. More recently, additional immunological mechanisms are understood to contribute to the development of cytopenias. For instance, immune activation and hyper inflammation-driven cytopenias are documented in the context of disorders such as hemophagocytic lymphohistiocytosis; cytokine-based injury has been described in the context of hematopoietic defects such as in GATA2 haploinsufficiency; and proliferation of large granular lymphocytes may also be documented in the context of cytopenias. 


In certain circumstances, immunologic underpinnings of hematological phenotypes may be exploited and defined even better within the context of the application of targeted therapies. Although the identification of an underlying genetic aberration and the clarification of its pathophysiology has been vital to the use of targeted therapeutics, it is also critical to understand the common pathobiology by enhanced immune phenotyping and functional tests in order to deduct potential treatment targets, irrespective of genetic aberrations, as the majority of immune-mediated cytopenias e.g., common variable or combined immunodeficiency with immune dysregulation, may lack an identifiable genetic etiology.  


In this Research Topic, we invite authors to submit manuscripts that incorporate and highlight these examples, as well as broaden our understanding of the vast array of immunologic underpinnings, ultimately leading to improvement in the management of hematologic manifestations of disease. Emphasis will be placed on the recent advancements in immunobiology and genetics of cytopenias and immunohematology disorders. In addition, manuscripts addressing unique clinical perspectives, immune biomarkers for high-risk cytopenias, responses to therapy including novel targeted and semi-targeted personalized immune-modulatory strategies, and long-term outcomes are welcome. 


We welcome the submission and contribution of Original Research, Case Report, Review, Mini-review, and Perspective articles related to, but not limited to, the following areas:


1. Early diagnosis of Inborn error of Immunity (IEI) in patients with single lineage and complex immune cytopenia including Evans syndrome, and understanding the interplay of IEI and immune cytopenia 

2. Understanding the risk of progression of complex immune cytopenia with occult immune abnormalities, to a broader immune dysregulation and immunodeficiency 

3. Identifying immune cytopenias with high risk for underlying IEI, including nonresponse to traditional intervention. 

4. Long-term immune morbidity (e.g., autoimmunity, lymphoproliferation, immune deficiency, malignancies) of complex immune cytopenia either due to disease-intrinsic or extrinsic risks such as infections, chronic inflammation, or treatment effects (e.g., post-rituximab or long-term mycophenolate mofetil treatment).

5. Immunobiology of cytopenia which shed additional insight on the role of B and plasma cells, T cells, NK cells, dendritic cells, monocyte/ macrophage in immune cytopenias 

6. Second- and third-line therapeutic management of immune cytopenia including IEI-targeted and nontargeted approaches

7. Early identification and management of immuno-hematopoietic defects such as GATA2 haploinsufficiency, SAMD9, SAMD9L and IRF8-associated defects. 

8. The role of inflammatory stress in contributing to the progression of cytopenia in immune-hematopoietic defects 

9. Large granular lymphocytosis associated cytopenia and IEI 

10. Hyperinflammation and HLH due to IEI that are not directly associated with cytotoxicity defect

11. Secondary immune abnormalities in the setting of hyperinflammatory disorder 

12. Association of leukocytosis (including neutrophilia and lymphocytosis) with IEI eg. LAD, CBM complex defects 

13. Association of eosinophilia with IEI eg. CARD11 defects

14. Immune dysregulation from checkpoint inhibitors leading to hematological manifestations

15. Nonmalignant lymphoproliferation associated with IEI





Topic Editor Dr. Seidel's Research Unit received financial support from Novartis, AMGEN, and Takeda. The other Topic Editors declare no competing interests with regard to the Research Topic subject.


Keywords: Immuno-Hematology, Immune cytopenia, Non classical HLH Lymphocytic variant, Hyper eosinophilic syndrome


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Immune cytopenias, impacting a single cell lineage or multiple cell lineages, are a frequently encountered primary manifestation of inborn errors of immunity (IEI). Increased awareness and greater clinical availability of diagnostic immunology and molecular-genetic testing, as a means to identify these processes, offer a unique opportunity to provide an early and accurate diagnosis, and to characterize the natural history and treatment responses of an underlying disorder.


Traditionally, autoantibody-mediated processes have been considered the predominant immunologic driver of immune cytopenias. More recently, additional immunological mechanisms are understood to contribute to the development of cytopenias. For instance, immune activation and hyper inflammation-driven cytopenias are documented in the context of disorders such as hemophagocytic lymphohistiocytosis; cytokine-based injury has been described in the context of hematopoietic defects such as in GATA2 haploinsufficiency; and proliferation of large granular lymphocytes may also be documented in the context of cytopenias. 


In certain circumstances, immunologic underpinnings of hematological phenotypes may be exploited and defined even better within the context of the application of targeted therapies. Although the identification of an underlying genetic aberration and the clarification of its pathophysiology has been vital to the use of targeted therapeutics, it is also critical to understand the common pathobiology by enhanced immune phenotyping and functional tests in order to deduct potential treatment targets, irrespective of genetic aberrations, as the majority of immune-mediated cytopenias e.g., common variable or combined immunodeficiency with immune dysregulation, may lack an identifiable genetic etiology.  


In this Research Topic, we invite authors to submit manuscripts that incorporate and highlight these examples, as well as broaden our understanding of the vast array of immunologic underpinnings, ultimately leading to improvement in the management of hematologic manifestations of disease. Emphasis will be placed on the recent advancements in immunobiology and genetics of cytopenias and immunohematology disorders. In addition, manuscripts addressing unique clinical perspectives, immune biomarkers for high-risk cytopenias, responses to therapy including novel targeted and semi-targeted personalized immune-modulatory strategies, and long-term outcomes are welcome. 


We welcome the submission and contribution of Original Research, Case Report, Review, Mini-review, and Perspective articles related to, but not limited to, the following areas:


1. Early diagnosis of Inborn error of Immunity (IEI) in patients with single lineage and complex immune cytopenia including Evans syndrome, and understanding the interplay of IEI and immune cytopenia 

2. Understanding the risk of progression of complex immune cytopenia with occult immune abnormalities, to a broader immune dysregulation and immunodeficiency 

3. Identifying immune cytopenias with high risk for underlying IEI, including nonresponse to traditional intervention. 

4. Long-term immune morbidity (e.g., autoimmunity, lymphoproliferation, immune deficiency, malignancies) of complex immune cytopenia either due to disease-intrinsic or extrinsic risks such as infections, chronic inflammation, or treatment effects (e.g., post-rituximab or long-term mycophenolate mofetil treatment).

5. Immunobiology of cytopenia which shed additional insight on the role of B and plasma cells, T cells, NK cells, dendritic cells, monocyte/ macrophage in immune cytopenias 

6. Second- and third-line therapeutic management of immune cytopenia including IEI-targeted and nontargeted approaches

7. Early identification and management of immuno-hematopoietic defects such as GATA2 haploinsufficiency, SAMD9, SAMD9L and IRF8-associated defects. 

8. The role of inflammatory stress in contributing to the progression of cytopenia in immune-hematopoietic defects 

9. Large granular lymphocytosis associated cytopenia and IEI 

10. Hyperinflammation and HLH due to IEI that are not directly associated with cytotoxicity defect

11. Secondary immune abnormalities in the setting of hyperinflammatory disorder 

12. Association of leukocytosis (including neutrophilia and lymphocytosis) with IEI eg. LAD, CBM complex defects 

13. Association of eosinophilia with IEI eg. CARD11 defects

14. Immune dysregulation from checkpoint inhibitors leading to hematological manifestations

15. Nonmalignant lymphoproliferation associated with IEI





Topic Editor Dr. Seidel's Research Unit received financial support from Novartis, AMGEN, and Takeda. The other Topic Editors declare no competing interests with regard to the Research Topic subject.


Keywords: Immuno-Hematology, Immune cytopenia, Non classical HLH Lymphocytic variant, Hyper eosinophilic syndrome


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

30 July 2021 Abstract
30 November 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

30 July 2021 Abstract
30 November 2021 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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