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Article ; Online: CDC (Cindy and David’s Conversations) game

Zhanshan (Sam) Ma / Liexun Yang

iScience, Vol 26, Iss 7, Pp 107079- (2023)

Advising President to survive pandemic

2023

Abstract: Summary: Ongoing debates on anti-COVID19 policies have been focused on coexistence-with versus zero-out (virus) strategies, which can be simplified as “always open (AO)” versus “always closed (AC).” We postulate that a middle ground, dubbed LOHC (low- ... ...

Abstract	Summary: Ongoing debates on anti-COVID19 policies have been focused on coexistence-with versus zero-out (virus) strategies, which can be simplified as “always open (AO)” versus “always closed (AC).” We postulate that a middle ground, dubbed LOHC (low-risk-open and high-risk-closed), is likely favorable, precluding obviously irrational HOLC (high-risk-open and low-risk-closed). From a meta-strategy perspective, these four policies cover the full spectrum of anti-pandemic policies. By emulating the reality of anti-pandemic policies today, the study aims to identify possible cognitive gaps and traps by harnessing the power of evolutionary game-theoretic analysis and simulations, which suggest that (1) AO and AC seem to be “high-probability” events (0.412–0.533); (2) counter-intuitively, the middle ground—LOHC—seems to be small-probability event (0.053), possibly mirroring its wide adoptions but broad failures. Besides devising specific policies, an equally important challenge seems to deal with often hardly avoidable policy transitions along the process from emergence, epidemic, through pandemic, to endemic state.
Keywords	Public health ; Information system model ; Decision science ; Science ; Q
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: T-helper-2 cells and atopic disease: lessons learnt from inborn errors of immunity.

Ma, Cindy S

Current opinion in immunology

2023 Volume 81, Page(s) 102298

Abstract: Inborn errors of immunity (IEI) are caused by monogenic variants that affect the host response to bacterial, viral, and fungal pathogens. As such, individuals with IEI often present with severe, recurrent, and life-threatening infections. However, the ... ...

Abstract	Inborn errors of immunity (IEI) are caused by monogenic variants that affect the host response to bacterial, viral, and fungal pathogens. As such, individuals with IEI often present with severe, recurrent, and life-threatening infections. However, the spectrum of disease due to IEI is very broad and extends to include autoimmunity, malignancy, and atopic diseases such as eczema, atopic dermatitis, and food and environmental allergies. Here, I review IEI that affect cytokine signaling pathways that dysregulate CD4
MeSH term(s)	Humans ; Autoimmunity ; Cell Differentiation ; Dermatitis, Atopic ; Food ; Hypersensitivity ; Th2 Cells
Language	English
Publishing date	2023-03-02
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2023.102298
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Article ; Online: Inborn errors of immunity: the Goldilocks effect-susceptibility to disease due to a little too much or a little too little.

Ma, Cindy S / Tangye, Stuart G

Clinical and experimental immunology

2023 Volume 212, Issue 2, Page(s) 93–95

Language	English
Publishing date	2023-04-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxad039
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Article ; Online: Inborn Errors of Immunity: A Role for Functional Testing and Flow Cytometry in Aiding Clinical Diagnosis.

Ma, Cindy S / Freeman, Alexandra F / Fleisher, Thomas A

The journal of allergy and clinical immunology. In practice

2023 Volume 11, Issue 6, Page(s) 1579–1591

Abstract: With the exponential discovery of new inborn errors of immunity (IEI), it is becoming increasingly difficult to differentiate between a number of the more recently defined disorders. This is compounded by the fact that although IEI primarily present with ...

Abstract	With the exponential discovery of new inborn errors of immunity (IEI), it is becoming increasingly difficult to differentiate between a number of the more recently defined disorders. This is compounded by the fact that although IEI primarily present with immunodeficiency, the spectrum of disease is broad and often extends to features typical of autoimmunity, autoinflammation, atopic disease, and/or malignancy. Here we use case studies to discuss the laboratory and genetic tests used that ultimately led to the specific diagnoses.
MeSH term(s)	Humans ; Flow Cytometry ; Autoimmunity ; Genetic Testing
Language	English
Publishing date	2023-04-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2843237-X
ISSN	2213-2201 ; 2213-2198
ISSN (online)	2213-2201
ISSN	2213-2198
DOI	10.1016/j.jaip.2023.03.049
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Article ; Online: Cytokine-mediated STAT-dependent pathways underpinning human B-cell differentiation and function.

Tangye, Stuart G / Pathmanandavel, Karrnan / Ma, Cindy S

Current opinion in immunology

2023 Volume 81, Page(s) 102286

Abstract: B cells are fundamental to host defence against infectious diseases; indeed, the ability of humans to elicit robust antibody responses following exposure to foreign antigens underpins long-lived humoral immunity and serological memory, as well as the ... ...

Abstract	B cells are fundamental to host defence against infectious diseases; indeed, the ability of humans to elicit robust antibody responses following exposure to foreign antigens underpins long-lived humoral immunity and serological memory, as well as the success of most currently administered vaccines. However, B cells also have a dark side - they can cause myriad diseases, including autoimmunity, atopy, allergy and malignancy. Thus, it is critical to understand the molecular requirements for generating effective, high-affinity, specific immune responses following natural infection or vaccination, as well as for constraining B-cell function to mitigate B-cell-mediated immune dyscrasias. In this review, we discuss recent developments that have been derived from the identification and detailed analysis of individuals with inborn errors of immunity that disrupt cytokine signalling, resulting in immune dysregulatory conditions. These studies have defined fundamental cytokine/cytokine receptor/signal transducer and activator of transcription (STAT) signalling pathways that are critical for the generation and maintenance of human memory B-cell and plasma cell subsets during host defence, as well as revealed mechanisms of disease pathogenesis causing immune deficiency, autoimmunity and atopy. More importantly, these studies have identified molecules that could be targeted to either enhance humoral immunity in the settings of infection or vaccination, or attenuate humoral immunity that contributes to antibody-mediated autoimmunity or allergy.
MeSH term(s)	Humans ; Cytokines ; B-Lymphocytes ; Immunity, Humoral ; Cell Differentiation ; Hypersensitivity
Chemical Substances	Cytokines
Language	English
Publishing date	2023-02-08
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2023.102286
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Article ; Online: Molecular regulation and dysregulation of T follicular helper cells - learning from inborn errors of immunity.

Tangye, Stuart G / Ma, Cindy S

Current opinion in immunology

2021 Volume 72, Page(s) 249–261

Abstract: The production of high-affinity antibodies is a key feature of the vertebrate immune system. Antibodies neutralize and clear pathogens, thereby protecting against infectious diseases. However, dysregulated production of antibodies can cause immune ... ...

Abstract	The production of high-affinity antibodies is a key feature of the vertebrate immune system. Antibodies neutralize and clear pathogens, thereby protecting against infectious diseases. However, dysregulated production of antibodies can cause immune pathologies, such as autoimmunity and immune deficiency. Long-lived humoral immunity depends on B-cell help provided by T follicular helper (Tfh) cells, which support the differentiation of antigen (Ag)-specific B cells into memory and plasma cells. Tfh cells are generated from naïve CD4
MeSH term(s)	Autoimmunity ; Biomarkers ; Cytokines/metabolism ; Gene Expression Regulation ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genetic Variation ; Humans ; Immunity/genetics ; Lymphocyte Count ; Receptors, Cytokine/genetics ; Receptors, Cytokine/metabolism ; Signal Transduction ; T Follicular Helper Cells/immunology ; T Follicular Helper Cells/metabolism ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism
Chemical Substances	Biomarkers ; Cytokines ; Receptors, Cytokine
Language	English
Publishing date	2021-07-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1035767-1
ISSN	1879-0372 ; 0952-7915
ISSN (online)	1879-0372
ISSN	0952-7915
DOI	10.1016/j.coi.2021.06.011
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Article ; Online: The ups and downs of STAT3 function: too much, too little and human immune dysregulation.

Mackie, Joseph / Ma, Cindy S / Tangye, Stuart G / Guerin, Antoine

Clinical and experimental immunology

2023 Volume 212, Issue 2, Page(s) 107–116

Abstract: The STAT3 story has almost 30 years of evolving history. First identified in 1994 as a pro-inflammatory transcription factor, Signal Transducer and Activator of Transcription 3 (STAT3) has continued to be revealed as a quintessential pleiotropic ... ...

Abstract	The STAT3 story has almost 30 years of evolving history. First identified in 1994 as a pro-inflammatory transcription factor, Signal Transducer and Activator of Transcription 3 (STAT3) has continued to be revealed as a quintessential pleiotropic signalling module spanning fields including infectious diseases, autoimmunity, vaccine responses, metabolism, and malignancy. In 2007, germline heterozygous dominant-negative loss-of-function variants in STAT3 were discovered as the most common cause for a triad of eczematoid dermatitis with recurrent skin and pulmonary infections, first described in 1966. This finding established that STAT3 plays a critical non-redundant role in immunity against some pathogens, as well as in the connective tissue, dental and musculoskeletal systems. Several years later, in 2014, heterozygous activating gain of function germline STAT3 variants were found to be causal for cases of early-onset multiorgan autoimmunity, thereby underpinning the notion that STAT3 function needed to be regulated to maintain immune homeostasis. As we and others continue to interrogate biochemical and cellular perturbations due to inborn errors in STAT3, we will review our current understanding of STAT3 function, mechanisms of disease pathogenesis, and future directions in this dynamic field.
MeSH term(s)	Humans ; Autoimmunity/genetics ; Autoimmunity/immunology ; Mutation/genetics ; STAT3 Transcription Factor/immunology ; STAT3 Transcription Factor/metabolism ; Immunity/genetics ; Immunity/immunology ; Immune System Diseases/genetics ; Immune System Diseases/immunology
Chemical Substances	STAT3 protein, human ; STAT3 Transcription Factor
Language	English
Publishing date	2023-02-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	218531-3
ISSN	1365-2249 ; 0009-9104 ; 0964-2536
ISSN (online)	1365-2249
ISSN	0009-9104 ; 0964-2536
DOI	10.1093/cei/uxad007
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Article ; Online: The trajectory of human B-cell function, immune deficiency, and allergy revealed by inborn errors of immunity.

Tangye, Stuart G / Mackie, Joseph / Pathmanandavel, Karrnan / Ma, Cindy S

Immunological reviews

2023 Volume 322, Issue 1, Page(s) 212–232

Abstract: The essential role of B cells is to produce protective immunoglobulins (Ig) that recognize, neutralize, and clear invading pathogens. This results from the integration of signals provided by pathogens or vaccines and the stimulatory microenvironment ... ...

Abstract	The essential role of B cells is to produce protective immunoglobulins (Ig) that recognize, neutralize, and clear invading pathogens. This results from the integration of signals provided by pathogens or vaccines and the stimulatory microenvironment within sites of immune activation, such as secondary lymphoid tissues, that drive mature B cells to differentiate into memory B cells and antibody (Ab)-secreting plasma cells. In this context, B cells undergo several molecular events including Ig class switching and somatic hypermutation that results in the production of high-affinity Ag-specific Abs of different classes, enabling effective pathogen neutralization and long-lived humoral immunity. However, perturbations to these key signaling pathways underpin immune dyscrasias including immune deficiency and autoimmunity or allergy. Inborn errors of immunity that disrupt critical immune pathways have identified non-redundant requirements for eliciting and maintaining humoral immune memory but concomitantly prevent immune dysregulation. Here, we will discuss our studies on human B cells, and how our investigation of cytokine signaling in B cells have identified fundamental requirements for memory B-cell formation, Ab production as well as regulating Ig class switching in the context of protective versus allergic immune responses.
MeSH term(s)	Humans ; B-Lymphocytes ; Immunity, Humoral ; Antibody Formation ; Hypersensitivity ; Germinal Center ; Immunologic Deficiency Syndromes
Language	English
Publishing date	2023-11-20
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/imr.13288
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Article ; Online: Human T Follicular Helper Cells in Primary Immunodeficiency: Quality Just as Important as Quantity.

Ma, Cindy S

Journal of clinical immunology

2016 Volume 36 Suppl 1, Page(s) 40–47

Abstract: T follicular helper (Tfh) cells are a subset of effector CD4(+) T cells specialised to induce Ab production by B cells. This review highlights some of the recent advances in the field of human Tfh cells that have come from the study of primary ... ...

Abstract	T follicular helper (Tfh) cells are a subset of effector CD4(+) T cells specialised to induce Ab production by B cells. This review highlights some of the recent advances in the field of human Tfh cells that have come from the study of primary immunodeficiencies. In particular it is increasingly evident that the quality of the Tfh cells that are generated, is just as important as the quantity.
MeSH term(s)	Biomarkers ; Cytokines/metabolism ; Disease Susceptibility ; Gene Expression Regulation ; Humans ; Immunologic Deficiency Syndromes/etiology ; Immunologic Deficiency Syndromes/metabolism ; Phenotype ; Receptors, Cytokine/metabolism ; Signal Transduction ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; T-Lymphocytes, Helper-Inducer/immunology ; T-Lymphocytes, Helper-Inducer/metabolism ; Transcription Factors/metabolism
Chemical Substances	Biomarkers ; Cytokines ; Receptors, Cytokine ; Transcription Factors
Language	English
Publishing date	2016-03-10
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-016-0257-6
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Article ; Online: Inborn errors of human B cell development, differentiation, and function.

Tangye, Stuart G / Nguyen, Tina / Deenick, Elissa K / Bryant, Vanessa L / Ma, Cindy S

The Journal of experimental medicine

2023 Volume 220, Issue 7

Abstract: B cells develop from hematopoietic stem cells in the bone marrow. Once generated, they serve multiple roles in immune regulation and host defense. However, their most important function is producing antibodies (Ab) that efficiently clear invading ... ...

Abstract	B cells develop from hematopoietic stem cells in the bone marrow. Once generated, they serve multiple roles in immune regulation and host defense. However, their most important function is producing antibodies (Ab) that efficiently clear invading pathogens. This is achieved by generating memory B cells that rapidly respond to subsequent Ag exposure, and plasma cells (PCs) that continually secrete Ab. These B cell subsets maintain humoral immunity and host protection against recurrent infections for extended periods of time. Thus, the generation of antigen (Ag)-specific memory cells and PCs underlies long-lived serological immunity, contributing to the success of most vaccines. Our understanding of immunity is often derived from animal models. However, analysis of individuals with monogenic defects that disrupt immune cell function are unprecedented models to link genotypes to clinical phenotypes, establish mechanisms of disease pathogenesis, and elucidate critical pathways for immune cell development and differentiation. Here, we review fundamental breakthroughs in unraveling the complexities of humoral immunity in humans that have come from the discovery of inborn errors disrupting B cell function.
MeSH term(s)	Animals ; Humans ; B-Lymphocytes ; Plasma Cells ; Cell Differentiation ; Immunity, Humoral ; B-Lymphocyte Subsets ; Antibodies/metabolism
Chemical Substances	Antibodies
Language	English
Publishing date	2023-06-05
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20221105
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